The effect of iron (III) hydroxide sucrose complex (Ranofer) and other iron preparations on body iron store in long term hemodialysis patients – A retrospective cohort study

The effect of iron (III) hydroxide sucrose complex (Ranofer) and other iron preparations on body iron store in long term hemodialysis patients – A retrospective cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The effect of iron (III) hydroxide sucrose complex (Ranofer) and other iron preparations on body iron store in long term hemodialysis patients – A retrospective cohort study Chye Chung Gan, Nurul Azwani Nadia Mansor, Soo Kun Lim This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2057589/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Intravenous iron is important in the management of iron deficiency and renal anemia among hemodialysis patients. Iron sucrose is one of the commonly used iron preparations in Malaysia. Our study objective is to assess the iron status changes in hemodialysis patients who have been initiated on intravenous (IV) iron-(III)-hydroxide-sucrose-complex (Ranofer) and other IV iron preparations (non-Ranofer) under real-world clinical settings over a six-month observation period. Methods: A retrospective cohort study was conducted to analyze the effectiveness and safety profiles of IV-Ranofer and IV-non-Ranofer on body iron stores in end-stage kidney disease (ESKD) patients across dialysis centers in Selangor from 01.01.2017 to 31.08.2020. Two-hundred-twenty subjects were included in the final analysis. Clinical response is defined as an improvement on serum ferritin > 100 microgram/L and TSAT > 20% at any point within the period of 6-months. Results: Of the 220-subjects, 124 (56.4%) achieved clinical response, in which the Ranofer group recorded 56 (51.9%) and the non-Ranofer group recorded 68 (60.7%) respectively, with no difference in between groups (p = 0.185). However, hypotension (10.2% vs 1.8%, p < 0.01), and headache (6.5% vs 0.9%, p < 0.05), occurred more frequently in Ranofer group compared to non-Ranofer group. Seventy-eight (72.9%) in the Ranofer group and 79 (70.5%) subjects in the non-Ranofer group managed to sustain Hb ≥ 10 g/dL at the end of the study (p = 0.69). Conclusions: Ranofer provides similar efficacy compared with other iron preparations for ESKD undergoing long-term hemodialysis in Malaysia. Ranofer is well-tolerated for the patients on hemodialysis. Hypotension and headache were observed to be slightly higher in the Ranofer group, however, the severity and the cause-effect relationship could not be ascertained due to the retrospective nature of this study. The adverse events were expected, and these outcomes were expected to be similar to other iron preparations in the real clinical setting. This study was conducted in accordance with the Declaration of Helsinki and approved by the local ethical committees. Intravenous (IV) iron-(III)-hydroxide-sucrose-complex iron deficiency anemia hemodialysis Figures Figure 1 Figure 2 Background Iron deficiency is a significant contributor to renal anemia, particularly in hemodialysis (HD) population. The causes are often multifactorial but mainly due to increased iron demand due to the use of erythropoietin stimulating agents (ESAs) and blood loss. 1 Anemia in chronic kidney disease (CKD) is correlated with increased cardiovascular disease, cognitive impairment, hospital admissions, mortality, and reduced quality of life. 2 Intravenous (IV) iron supplementation is an important element in the treatment landscape of anemia management among the HD patients. 3 Iron carbohydrate preparations are one of the non-biological complex drugs (NBCD). The NBCDs is expressed as (1) consisting of a complex multitude of closely related structures; (2) the entire multitude is the active pharmaceutical ingredient; (3) the properties cannot be fully described by physicochemical analysis and (4) the consistent, tightly regulated manufacturing process is fundamental to reproduce the product. 4 The crucial role of iron therapy in a variety of clinical conditions has led to the advancement and introduction of new iron carbohydrate complexes (e.g. ferric carboxymaltose) and iron sucrose similar (ISS) preparations. 5 ISS has been marketed under the supposition that they are identical to the originator iron sucrose (IS). However, reproducing the physicochemical identity of IS is challenging. 6 Achieving therapeutic interchangeability with the originator is challenging. IV iron formulations take the form of iron carbohydrate complexes in which an iron-containing mineral core is bounded by a carbohydrate ligand for stability. The pharmacologic and biologic properties of the complex are influenced by the different sizes and structures of the mineral core and the carbohydrate shell. 7 The degree of stability of iron carbohydrate complexes is critical. Weakly bounded iron may dissociate from the complex and catalyze the generation of reactive oxygen species. 8 Stability is highly reliant on the manufacturing method. Supporting evidence that shows pharmaceutical equivalence for ISS or other iron preparations based on comparable physicochemical properties may not be adequate for NBCDs. This is because they cannot be fully characterized from a physicochemical perspective. In this study, we aim to assess the iron status changes of HD patients who have been initiated on IV iron (III) hydroxide sucrose complex (Ranofer) and other IV iron preparations (non-Ranofer) under real-world clinical settings over a six-month observation period. Besides, we would like to assess the safety profile and the hemoglobin level changes in patients given IV Ranofer and non-Ranofer. Methods Study design This was a retrospective cohort study that analyzed the effectiveness and safety profiles of Ranofer (IV iron-(III)-hydroxide sucrose complex) and non-Ranofer [Venofer, iron-(III)-hydroxide sucrose complex; Avofer, iron-(III)-hydroxide sucrose complex; Cosmofer, iron-(III)-hydroxide dextran complex] on body iron store in ESKD patients undergoing long term hemodialysis from 11 different dialysis centers within the state of Selangor, Malaysia from January 2017 to August 2020. Patients were identified from the medical records and included in the study if they met the inclusion and exclusion criteria. The study collected information on demographics, clinical data, comorbidities, hospitalization, and procedure history, within one month before baseline. The safety outcome measures included the history of any of the following symptoms, i.e., hypotension, muscle cramps, headache, and nausea observed during six months from baseline. The date of the treatment initiation was considered as the “baseline”. Figure 1 below illustrates the study design described above: Point #1 refers to the study treatment initiation point where baseline data were collected. Point #2 refers to the “look back” period where the pre-treatment outcome variables were collected. Point #3 refers to the “look forward” period (6-months after IV iron initiation) where the outcome data (e.g., serum ferritin, transferrin saturation (TSAT), and Hb) were collected along with the study treatment data and time-varying factors (e.g., erythropoietin use). Study population Adult (age ≥ 18 years) with ESKD on long-term hemodialysis initiated intravenous iron therapy during the observation periods. Specific inclusion and exclusion criteria are listed below. Inclusion Criteria Patient with ESKD on regular (at least 3 4-hr sessions per week) long-term hemodialysis for at least 6 months. Initiated IV Ranofer or any other IV iron preparations during the determined study period. Persisted on the (respective) iron formulation for at least 5 consecutive doses. Hb < 12 g/dL, TSAT ≤ 30% and serum ferritin ≤ 800ng/mL within one month prior to treatment initiation. With at least one laboratory result available (within six months post-therapy initiation) indicating the post-therapy iron store level. Exclusion Criteria The patient was contraindicated for iron therapy. The patient had received blood transfusion one month before or after the initiation of iron therapy. Patient with known underlying hematological disorder other than iron deficiency anemia (documented within the period of observation). Patient with diagnosed retroviral disease (HIV). Exposure The exposure groups of this observational study are as follow: Ranofer exposure group was defined as subjects (fulfilling all inclusion and exclusion criteria listed above) who have initiated IV Ranofer during the defined observation period. Non-Ranofer exposure group was defined as subjects (fulfilling all inclusion and exclusion criteria listed above) who have initiated any IV iron preparations (other than Ranofer) during the defined observation period. Treatments and evaluations Below is a general description of the treatment and primary study endpoints (Table 1 .) Table 1 Treatment under investigation and primary study endpoints CKD, Chronic kidney disease; IV, Intravenous. Treatment under investigation Intravenous iron sucrose Replacement of iron stores found in hemoglobin, myoglobin, and enzymes; Indicated for the treatment of iron deficiency anemia associated with chronic kidney disease. Hemodialysis-dependent CKD: 100 mg elemental iron IV (injection or infusion over 2–5 min) per dialysis session not to exceed a total cumulative dose of 1000 mg divided into 3 doses/week Evaluation for primary study endpoints 1. Serum ferritin 9 Ferritin is the cellular storage protein for iron. It is present in small concentrations in blood, and the serum ferritin concentration normally correlates well with total-body iron stores, making its measurement important in the diagnosis of disorders of iron metabolism. 2. Transferrin saturation (TSAT) 10 The TSAT is the serum iron divided by the total iron-binding capacity (TIBC), which corresponds to circulating iron. The TIBC reflects transferrin, the protein to which virtually all iron in the blood is bound. The K/DOQI workgroups have determined that absolute iron deficiency, the absence or near absence of stainable iron in the bone marrow, correlates with TSAT < 20% and that there is a risk for iron overload when the TSAT exceeds 50%. These also are opinion-based and not evidence-based guidelines. CKD, Chronic kidney disease; IV, Intravenous. Endpoints Primary: Treatment success – defined as an improvement of serum ferritin of more than 100 microgram/L (highest recorded point) and an improvement of TSAT of more than 20% from baseline to the highest recorded point. Secondary: All-cause mortality within the six months of the defined observation period All-cause hospitalization within the six months of the defined observation period Documented adverse event-related symptoms on a medical chart, including hypotension, muscle cramps, headache, nausea, rash(es) and/or itchiness, wheezing and/or shortness of breath, swelling of the face, tongue, or throat. Exploratory: Absolute and relative serum hemoglobin improvement from baseline to: highest recorded point post-intervention. last recorded point within the six-month defined observation period. Data management A standardized paper-based Case-Report-Form (CRF) was developed and used to ensure that all data are collected in a standardized and consistent manner. Data on all the listed study variables, abstracted from the medical charts of each eligible study subject. Information not available in the medical charts were considered as missing and be coded as “NA”. Each eligible subject was prepared with one study-specific case folder that contained all the required CRFs. No identifying information was captured within those CRFs that required electronic transmission; only a unique ID was made available at the study sites in case reidentification is required for any study and non-study-related purpose. Decisions to reidentify the study subject are at the discretion of the participating investigators taking charge of the specific dialysis center. The received CRFs provided by the study sites underwent an initial screening process for quality checks. This is to ensure that the CRFs received are of adequate quality for the subsequent data entry purpose. The qualities for assessment are for instance range, missingness, etc. The data from paper CRF were entered into the EpiCollect5 database used for storing the study data. CRFs not meeting the required quality standards were returned to the study sites with a specific query raised to the site's study coordinator. All the queries and responses were documented in a log file. During the data entry process, a regular review of the study dataset was conducted once in the mid-phase of the study (approaching half of the target study size) and once at the end of the study before finalizing the study dataset (Database lock). Data review at this stage was intended to identify potential data errors not captured during the initial screening process e.g., outliers, free texts, etc. No source document verification was conducted for this study. Statistical methods Statistical analyses were performed using R Version 3.5.2. The statistical results were displayed using tables, listings, and/or graphs. For univariate descriptive analysis, all categorical variables were present with the following summary measures: Frequency (number of cases [n]) and Percentage (%) For continuous variables, the following summary measures were computed: Mean, Standard deviation (SD), Median, Interquartile range (IQR) and For bivariate descriptive analyses, all variables were presented using the same set of descriptive measures described above. All descriptive analyses were performed using the exposure group as the bivariate factor. All descriptive summaries stratified by the exposure group were tested for their statistical difference using chi-square for nominal variables, ANOVA test for parametric continuous variables, and Mann-Whitney U test or Kruskal Wallis test for non-parametric variables without adjustment of multiple testing. When the variables have two levels, paired sample t-test for parametric variables and Wilcoxon test for non-parametric variables were used. Primary Analyses The treatment success was computed as Iron Replacement Achieved, IRA: $$IRA=\frac{Number of cases achieving the defined criteria of iron repletion}{Total number of cases}$$ Treatment success was calculated for the overall cohort and stratified by the exposure group (i.e. Ranofer group and non-Ranofer group). A crude comparison of the treatment success was made and the difference between the two stratums was tested for statistical significance using the chi-square test. Secondary Analyses All secondary endpoints were summarized with the following measures: Frequency (n) for the overall cohort, and stratified by the exposure variable (i.e. Ranofer vs. non-Ranofer) Percentage/proportion for the overall cohort, and stratified by the exposure variable Crude comparisons between the exposure strata were performed using the chi-square test. Exploratory Analyses The below list of statistical summary measures for this endpoint and objective was prepared for all the recordings of Hb during the observation period: Mean & standard deviation (SD), and Median & interquartile range (IQR) Comparisons were made between the Ranofer group vs. non-Ranofer within each recording period (i.e. baseline reading, 2nd reading, 3rd reading, and all subsequent reading where applicable). ANOVA test, Mann-Whitney U test, or Kruskal Wallis test was used to examine the probability of the two mean/distribution being similar. A two-sided p-value of ≤ 0.05 will be considered as a statistically significant difference between the two comparators. The hemoglobin change from baseline was computed as per below: For absolute Hb change from baseline to the highest recorded point post-intervention or last recorded point within the six-month defined observation period, the following formula will be used: $$Absolute Hb change=(highest recorded value or last recorded value-baseline value)$$ For relative Hb change from baseline to the highest recorded point post-intervention or last recorded point within the six-month defined observation period, the following formula was used: $$Relative Hb change=\frac{(highest recorded value or last recorded value-baseline value)}{baseline value}$$ Similarly, comparisons were made between the Ranofer group vs. the non-Ranofer group for the above exploratory endpoints. ANOVA test, Mann-Whitney U test, or Kruskal Wallis test was used to examine the probability of the two mean/distribution being similar. A two-sided p-value of ≤ 0.05 was considered as a statistically significant difference between the two comparators. A linear regression model was used to examine the relationship between the exposure variable (Ranofer vs. non-Ranofer) in the primary and exploratory outcome measure (achievement of iron repletion and change of Hb from baseline). A set of bivariate regression analyses was performed for the below baseline variables in addition to the exposure variable: age, gender, ethnicity, BMI, smoking status, Charlson comorbid score, baseline BP, baseline ferritin, baseline TSAT, baseline Hb, duration of dialysis, IV iron cumulative dose, EPO cumulative dose, baseline serum albumin (g/dL), baseline serum PTH (pg/mL), baseline Kt/V, and history of hospitalization. All variables with a p-value < 0.1 detected in the bivariate regression model were further considered for multivariate regression analysis. The two-sided significant level of 0.05 will be used to reject the null hypothesis. Results During the study period from January 2017 to August 2020, a total of 291 subjects were screened and we obtained a dataset containing 220 complete subject cases for the intended analysis. Of the 220 datasets from the primary analysis, one subject was excluded from exploratory analysis due to missing outcome data. The subjects' screening process is shown in Fig. 2 . Demographic and baseline characteristics Most of the patients were male (57.70%) with the mean age of 55.24 ± 14.00 years and Malaysian Chinese descendants made up 40.5% of study subjects followed by 37.7% Malay, 21.4% Indian, and 0.5% others. The median BMI was 24.08 with interquartile-range (IQR) of 21.11–27.32 kg/m 2 . Median dialysis vintage was 3.00 years with IQR of 1.00–5.00 years and the median Kt/V was 1.30 with IQR of 1.10–1.50, in which 150 (72.1%) of the subjects achieved Kt/V of ≥ 1.2. The most common dialysis access was AV-Fistula (85.5%), followed by catheter (13.1%) and AV-Graft (1.4%). Charlson index score recorded a median of 2 with IQR of 1–3. Of the total subjects, 152 (69.1%) have hypertension, 75 (34.1%) have diabetes treated with insulin, 6 (2.7%) have a history of myocardial infarction, 4 (1.8%) has a stroke with a deficit, 6 (2.7%) have a history of hospitalization 1 month before study, and 1 (0.5%) has surgical procedure 1 month before the study. The difference in the baseline characteristics between the Ranofer group and the non-Ranofer group was statistically insignificant (Table 2 ). Table 2 Baseline characteristics Table 2 : Baseline characteristic All Subjects (N = 220) Ranofer® (N = 108) Non-Ranofer® (N = 112) p-value Demographic Age – years Mean ± SD (95% CI) 55.24 ± 14.00 (53.83, 58.72) 54.17 ± 14.89 (51.33, 57.01) 56.28 ± 13.07 (53.38, 57.10) 0.265 Gender – n (%) Male 127 (57.7%) 63 (58.3%) 64 (57.1%) 0.858 Female 93 (42.3%) 45 (41.7%) 48 (42.9%) Ethnicity – n (%) Malay 83 (37.7%) 44 (40.7%) 39 (34.8%) Chinese 89 (40.5%) 39 (36.1%) 50 (44.6%) 0.427 Indian 47 (21.4%) 25 (23.1%) 22 (19.6%) Others 1 (0.5%) 0 (0.0%) 1 (0.9%) Height – cm Median (IQR) 162.00 (156.00, 168.00) 162.00 (156.00, 168.00) 163.00 (156.00, 167.75) 0.969 Missing data 22 (10%) 21 (19%) 1 (0.9%) Body weight – kg Median (IQR) 63.00 (53.33, 74.05) 63.05 (55.00, 74.40) 61.70 (52.50, 74.00) 0.659 BMI – kg/m 2 Median (IQR) 24.08 (21.11, 27.32) 24.09 (22.00, 27.11) 23.73 (20.74, 27.66) 0.568 Missing 22 (10%) 21 (19%) 1 (0.9%) Clinical characteristics Dialysis access AV-Fistula 188 (85.5%) 92 (85.2%) 96 (85.7%) 0.827 AV-Graft 3 (1.4%) 2 (1.9%) 1 (0.9%) Catheter 29 (13.2%) 14 (13.0%) 15 (13.4%) HD vintage, year(s) Median (IQR) 3.00 (1.00, 5.00) 3.00 (1.00, 5.00) 3.00 (1.00, 5.00) 0.858 HD vintage category 10 years 18 (8.2%) 9 (8.3%) 9 (8.0%) Baseline SBP, mmHg Mean ± SD (95% CI) 147.94 ± 24.61 (144.67, 151.21) 148.05 ± 23.90 (143.49, 152.61) 147.83 ± 25.38 (143.08, 152.59) 0.948 Baseline DBP, mmHg Mean ± SD (95% CI) 77.63 ± 14.27 (75.736, 79.528) 78.61 ± 13.38 (76.058, 81.164) 76.69 ± 15.07 (73.865, 79.510) 0.319 Comorbidities Charlson Index Score Median (IQR) 2.00 (1.00, 3.00) 2.00 (1.00, 3.00) 2.00 (1.00, 2.00) 0.330 Hypertension 152 (69.1%) 80 (74.1%) 72 (64.3%) 0.116 DM treated with insulin 75 (34.1%) 38 (35.2%) 37 (33.0%) 0.737 History of MI 6 (2.7%) 4 (3.7%) 2 (1.8%) 0.383 Stroke with deficit 4 (1.8%) 3 (2.8%) 1 (0.9%) 0.296 History of hospitalization one month prior IVIS 6 (2.7%) 5 (4.6%) 1 (0.9%) 0.089 History of surgical procedure one month prior IVIS 1 (0.5%) 1 (0.9%) 0 (0.0%) 0.307 Baseline laboratory results Median baseline serum ferritin, (ng/mL), IQR 278.50 (147.25, 457.75) 268.00 (137.75, 464.75) 284.00 (153.75, 453.25) 0.545 Baseline serum ferritin category 0.016 ≤ 100 32 (14.5%) 22 (20.4%) 10 (8.9%) > 100 188 (85.5%) 86 (79.6%) 102 (91.1%) Median baseline TSAT, IQR 19.00 (15.00, 23.00) 18.00 (15.00, 24.00) 19.00 (14.00, 23.00) 0.623 Baseline TSAT category 0.964 ≤ 20% 128 (58.2%) 63 (58.3%) 65 (58.0%) > 20% 92 (41.8%) 45 (41.7%) 47 (42.0%) Median baseline Hb (g/dL), IQR 9.70 (8.80, 10.60) 9.80 (9.10, 10.70) 9.70 (8.50, 10.50) 0.195 Baseline Hb category 0.964 < 10 92 (41.8%) 45 (41.7%) 47 (42.0%) ≥ 10 128 (58.2%) 63 (58.3%) 65 (58.0%) Median baseline serum albumin (g/dL), IQR 40.00 (38.00, 42.00) 41.00 (38.00, 42.00) 40.00 (37.75, 42.00) 0.238 Median baseline serum PTH (pmol/L), IQR 18.00 (6.00, 40.00) 29.00 (13.50, 60.00) 8.00 (4.00, 27.00) < 0.001 Missing 24 (10.9%) 17 (15.7%) 7 (6.3%) Baseline serum PTH category < 0.001 300 64 (32.7%) 42 (46.2%) 22 (21.0%) Missing 24 (10.9%) 17 (15.7%) 7 (6.3%) Median baseline Kt/V (mL,min), IQR 1.30 (1.10, 1.50) 1.30 (1.10, 1.40) 1.30 (1.20, 1.58) 0.029 Baseline Kt/V category 0.065 < 1.2 58 (27.9%) 33 (34.0%) 25 (22.5%) ≥ 1.2 150 (72.1%) 64 (66.0%) 86 (77.5%) Missing 12 (5.5%) 11 (10.2%) 1 (0.9%) Baseline erythropoietin category 0.979 Yes 218 (99.1%) 107 (99.1%) 111 (99.1%) No 2 (0.9%) 1 (0.9%) 1 (0.9%) Baseline clinical hematology characteristics The median baseline serum ferritin was 278.50 mg/L (IQR 147.25–457.75) and most subjects had baseline serum ferritin of more than 100 mg/L (85.5%). Meanwhile, the median TSAT at baseline was 19% (IQR 15.00–23.00). Around 92 (41.8%) subjects had TSAT more than 20% at baseline. The median baseline hemoglobulin level was 9.70 g/dL (IQR of 8.80–10.60). The result showed that the median baseline serum iPTH was 165.6 pg/mL (IQR 59.7–376.0) with 142 (72.4%) of the subjects having baseline iPTH of > 65 pg/mL. During the study, 218 (99.1%) of the subjects were using erythropoietin. Of all the subjects, 120 (56.1%) used Recormon, 85 (39.7%) used Mircera, 6 (2.8%) used Nesp, 3 (1.4%) used Eprex, and 4 with missing data. Ranofer cohort observed statistically significant differences from non-Ranofer cohort to have more subjects with baseline serum iron of ≤ 100ng/mL, median Kt/V of 65 pg/mL (Table 2 ). Primary Outcomes Of all the subjects, 124 (56.4%) achieved the primary outcome of iron repletion. Ranofer group recorded IRA of 56 subjects (51.9%) whereas non-Ranofer group recorded 68 subjects (60.7%) with no statistically significant difference between the two groups, p = 0.185 (Table 3 ). Table 3 Study Outcomes Table 3 : Study outcomes All Subjects (N = 220) Ranofer (N = 108) Non-Ranofer (N = 112) p-value Primary Iron repletion achieved (change in Serum ferritin > 100 mg/L and highest recorded TSAT > 20%) 124 (56.4%) 56 (51.9%) 68 (60.7%) 0.185 Change in serum ferritin > 100 mg/L (From baseline to highest recorded value) 159 (72.3%) 75 (69.4%) 84 (75.0%) 0.357 Change in serum ferritin (From baseline to highest recorded value) 224.50 (93.00, 487.00) 215.00 (78.00, 389.80) 243.50 (106.75, 505.25) 0.286 Change TSAT > 20% (From baseline to highest recorded value) 160 (72.7%) 75 (69.4%) 85 (75.9%) 0.283 Change in TSAT (From baseline to highest recorded value) 9.00 (3.60, 18.00) 8.00 (3.00, 17.03) 9.50 (4.00, 18.00) 0.245 Secondary Mortality at the end of the study 16 (7.3%) 6 (5.6%) 10 (8.9%) 0.335 Hypotension episode 13 (5.9%) 11 (10.2%) 2 (1.8%) 0.008* Muscle cramps 5 (2.3%) 3 (2.8%) 2 (1.8%) 0.622 Headache 8 (3.6%) 7 (6.5%) 1 (0.9%) 0.027* Nausea 5 (2.3%) 3 (2.8%) 2 (1.8%) 0.622 Rash(es) and/or itchiness 0 (0.0%) 0 (0.0%) 0 (0.0%) 0.787 Wheezing 0 (0.0%) 0 (0.0%) 0 (0.0%) 0.787 Swelling of the face, tongue, or throat 0 (0.0%) 0 (0.0%) 0 (0.0%) 0.787 History of hospitalization within 6 months after IVIS initiation 19 (8.6%) 15 (13.9%) 4 (3.6%) 0.006* History of surgical procedure 6 months after IVIS initiation 7 (3.2%) 5 (4.6%) 2 (1.8%) 0.230 Exploratory Absolute change in Hb (last reading - From baseline to last recorded value) 0.90 (0.00, 1.90) 0.80 (-0.15, 1.90) 1.00 (0.18, 1.83) 0.278 Relative change in Hb (last reading - From baseline to last recorded value) 0.09 (0.00, 0.21) 0.07 (-0.02, 0.21) 0.10 (0.02, 0.23) 0.234 Hb ≥ 10 (last reading) 157 (71.7%) 78 (72.9%) 79 (70.5%) 0.698 TSAT, Transferrin Saturation; Hb, Hemoglobin; IVIS, Intravenous Iron Sucrose. The association between biodemographic factors (age, sex, ethnicity, BMI, and smoking status) and clinical findings (duration of dialysis, BP, Charlson Index, serum ferritin, TSAT, IV iron cumulative dose, EPO dose, serum albumin, serum PTH, Kt/V and history of hospitalization) with iron repletion rate were tested in univariate logistic regression (Supplement 1). None of the factors were significantly associated with treatment success except for baseline serum ferritin and baseline TSAT with (OR, 0.998; 95% CI, 0.997–1.000; p-value = 0.030) and (OR, 0.935; 95% CI, 0.893–0.977; p-value = 0.004) respectively. These two variables were further tested in multivariate analysis to find out the magnitude of association with exposure variables (IV iron sucrose group – Ranofer) and treatment success. The odd ratio for baseline ferritin was statistically insignificant (OR, 0.999; 95% CI, 0.997–1.000; p-value = 0.077). The odds ratio for baseline TSAT shown statistically significant (OR, 0.941; 95% CI, 0.898–0.984; p-value = 0.009). This validates that this baseline ferritin is not a potential confounder in the analysis that could affect the results except TSAT (Supplement 1). However, the significance of the OR = 0.941 for TSAT remains questionable in the clinical setting. The median cumulative IV iron dose within 6-month of the study period was 1000.00 mg for all subjects. The median cumulative dose within 6-month is higher in the Ranofer group than the non-Ranofer group, 1000.00 mg (IQR 500.00–1300.00) and 600.00 mg (IQR 500.00–1000.00) respectively and it was a statistically significant difference (Table 4 ). However, the association between IRA and IV iron cumulative dose was not statistically significant in univariate analysis (Supplement 1). Table 4 Iron and EPO administration Table 4 : Iron and EPO administration All Subjects (N = 220) Ranofer (N = 108) Non-Ranofer (N = 112) p-value IV Iron administration Cumulative dose (mg) 1000.00 (500.00, 1000.00) 1000.00 (500.00, 1300.00) 600.00 (500.00, 1000.00) < 0.001* Days between administration 8.00 (7.00, 14.00) 8.00 (7.00, 11.25) 9.00 (7.00, 15.25) 0.333 Frequency of IVIS per administration (per month) 2.00 (2.00, 3.00) 2.00 (2.00, 3.00) 2.00 (2.00, 3.00) 0.102 Erythropoietin administration Starting dose - IU per week 6000.00 (4000.00, 8000.00) 7500.00 (4000.00, 9900.00) 6000.00 (4000.00, 7500.00) 0.125 Average dose - IU per week 4472.22 (2613.91, 6616.67) 4458.33 (2500.00, 6714.29) 4488.89 (2901.82, 6400.00) 0.641 IV, Intravenous; IVIS, Intravenous Iron Sucrose; IU, International Unit, IS, Iron Sucrose; ISS, Iron Sucrose Similar, Rx, Medical prescription. Meanwhile, the median dose per week of erythropoietin at baseline was 6000.00 IU/week (IQR 4000.00–8000.00). Erythropoietin with the unit of mcg was converted to IU using a conversion ratio of 200 IU = 1 mcg, based on several published literature. 13 – 15 We notice the reduction of median dose per week over the 6-month study period which was 4472.22 IU/week (2613.91–6616.67). A paired-samples t-test was conducted to compare the starting dose of erythropoietin (IU/week) and the average dose of erythropoietin used over the 6 months (IU/week) in the Ranofer and non-Ranofer group. In the Ranofer group, subjects needed less erythropoietin dosage over the 6-month study period M = 6431, SD = 4789.26; t(106) = 6.403, p < 0.001 after IV Iron infusion, as compared to baseline M = 14018.13, SD = 13108.03, and this was statistically significant. Similar trend was observed in the non-Ranofer group, where the median erythropoietin dosage over the 6-month study period after IV Iron infusion was M = 5904.12, SD = 4081.97; t(110) = 3.389, p = 0.001, as compared to baseline of M = 9720.72, SD = 13749.16, p = 0.001. The median dose per week over the 6-month study period in the Ranofer group did not differ from the non-Ranofer group, i.e., 4458.33 IU/week (IQR 2500.00–6714.29) and 4488.89 IU/week (IQR 2901.82–6400.00), respectively with p = 0.641 (Table 4 ). Secondary Outcomes Of the 220 patients included in safety analyses, 204 patients (92.7%) were reported to be alive at the end of the study. The most reported adverse events (AE) were hypotension (13 subjects, 5.9%), headache (8 subjects, 3.6%), nausea (5 subjects, 2.3%), and muscle cramps (5 subjects, 2.3%). Further analysis showed that subjects in Ranofer reported higher number of these AEs compared to other IV iron group; hypotension 11 (10.2%) versus 2 (1.8%); headache 7 (6.4%) versus 1 (0.9%); nausea 3 (2.8%) versus 2 (1.8%) and muscle cramps 3 (2.8%) versus 2 (1.8%), respectively (Table 3 ). Furthermore, 15 subjects out of 109 (13.9%) in the Ranofer group reported a history of hospitalization within 6-month post IV iron sucrose administration compared to the non-Ranofer group which recorded 4 subjects (3.6%) out of 112. (p = 0.006). Exploratory Outcomes The median absolute changes in Hb level from baseline to last recorded value over 6-month of the study observation period was slightly lower in Ranofer 0.80 g/dL (IQR − 0.15–1.90) compared to non-Ranofer group 1.00 g/dL (IQR 0.18–1.83), however, it was not statistically significant (p = 0.278). The same trend can be seen for median absolute change in Hb level from baseline to highest recorded value; i.e. Ranofer, 1.10 g/dL (IQR 0.3–2.1) and non-Ranofer, 1.30 g/dL (IQR 0.58–2.53) respectively (p = 0.318). Meanwhile, the median relative changes in Hb level from baseline to either last or highest recorded value over 6-month study period also displayed similar inclination, where non-Ranofer recorded slightly higher median changes 0.10 g/dL (IQR 0.02–0.23) and 0.13 g/dL (IQR 0.06–0.29 respectively; compared to Ranofer group 0.07 g/dL (IQR − 0.02–0.21) and 0.11 g/dL (IQR 0.03–021) respectively which was statistically insignificant (Table 3 ). Of 219 subjects included in exploratory analysis, 157 (71.7%) achieved Hb ≥ 10 g/dL at the last recording over 6-month of the study observation period. The breakdown by Ranofer and non-Ranofer group can be seen in Table 3 with no statistically significant difference between the 2 groups. Association analysis of the Hb changes with biodemographic factors (age, sex, ethnicity, BMI, and smoking status) and clinical findings (duration of dialysis, BP, Charlson Index, serum ferritin, TSAT, IV iron dose, EPO dose, serum albumin, serum PTH, Kt/V, and history of hospitalization) showed none of the factors were significantly associated when tested in univariate linear regression apart from baseline serum albumin and baseline Hb (Supplement 2.1 and 2.2). These variables were further tested in multivariate analysis to find out the magnitude of association with exposure variables (IV iron sucrose group – Ranofer) and Hb changes (absolute and relative). The beta coefficient and p-value remain comparable with no bigger changes (Supplement 2.1 and 2.2) compared to univariate analysis. Hence, further validates that this variable is not potentially confounding in the analysis that could affect the results. Discussion This study was designed to compare the efficacy of Ranofer with other intravenous iron preparations (non-Ranofer) retrospectively. The current data suggest that Ranofer has comparable efficacy compared to other commonly used IV iron brands in Malaysia (Venofer, Avofer, and Cosmofer). Six-month post-baseline, around half (56/108, 51.9%) of the subjects in the Ranofer group achieved the defined iron repletion status. Within the non-Ranofer group, 60.7% (68/112) achieved the defined iron repletion status. These results showed that Ranofer can offer comparable efficacy to other IV iron preparation available in the market. Even though the Ranofer group showed a higher cumulative dose of IV iron administration, this factor does not confound the iron replacement achievement in univariate analysis (Supplement 1). Besides, the IV Ranofer group was able to show a similar reduction in erythropoietin requirements after IV iron administration compared to the IV non-Ranofer group (Table 4 ). Our exploratory analysis which evaluated the changes of Hb status after 6 months of IV Ranofer therapy suggested similar results. Around 78 (72.9%) in the Ranofer group and 79 (70.5%) in the non-Ranofer group attained Hb ≥ 10 g/dL (at last recording value over the 6-month study period). These observations are consistent with previous studies of iron sucrose. Charytan et al 2001 reported that after 10 doses of iron sucrose injection, TSAT, serum ferritin, and Hb values increased significantly in patients with dialysis-dependency. 16 Fifty-eight patients have an improvement in iron status with TSAT > 20% and serum ferritin > 300 ng/mL and 60 patients were able to attain the target Hb level of 11.0 g/dL. 16 Similarly, a study in the Chinese population that explored the efficacy and safety of IV iron sucrose also disclosed that serum ferritin and TSAT levels also increased significantly after 8 and 12 weeks of treatment suggesting that ideal iron status in Chinese hemodialysis patients is TSAT 30–40% and serum ferritin 200–500 mg/L. 17 This study also reported that about 45 (64.3%) patients reached full treatment response defined as an increase in Hb ≥ 30 g/L. 17 These studies' findings are consistent with current study results which revealed that both IV iron sucrose or other IV iron preparations can produce almost comparable efficacy in serum iron store, TSAT and Hb improvement. Safety outcomes reported in the current study indicated that hypotension (10.2%) and headache (6.5%) are relatively higher in the Ranofer group compared to the non-Ranofer group (1.8% and 0.9%, respectively). However, based on information from the study of Venofer described in FDA package insert, hypotension and headache were quite prevalent especially in hemodialysis patients, with hypotension and headache reported around 91 (39.4%) and 29 (12.6%), respectively. 18 Meanwhile, Charyton et al 2001, stated that 12 (15.6%) patients receiving Venofer reported hypotension during the treatment period. 16 Several other studies in iron sucrose preparation and other iron preparations did show similar adverse events. 19–21 Thus, it is expected that Ranofer would yield similar side effects rates comparable with another iron brand. The difference in the current study possibly arises due to the nature of the retrospective study. In addition, the adverse events were observed throughout the 6 months of the study period and did not occur specifically within 1 week of the administration of the iron preparations. A retrospective study does not provide real-time information compared to a clinical trial. Without sufficiently complete follow-up information on the patients, this may lead to over or underestimation of the rate of adverse events in dialysis centers. With the limitations of the retrospective study, we are not able to draw a conclusion on the cause-effect relationship between IV Iron administration and the adverse events. The present study has several limitations related to the study design and data sources. Any observations or conclusions must be interpreted within the limitations of a retrospective study that may have selection bias, missing data, limited generalizability as these data derived from a limited number of dialysis centers around Selangor, and non-causal relationship nature of this study. A richer discussion to confirm these findings may be achieved with further randomized control trials. Conclusions The above analyses suggest that Ranofer has similar efficacy compared with other IV iron preparations for ESRD undergoing long-term hemodialysis despite the slight disadvantages of its adverse effect profile. Interpretation of the findings should account for the limitations of a retrospective study discussed above. Further investigation may provide stronger evidence to confirm the findings of this study. Abbreviations Abbreviations Description of abbreviations AE Adverse Event BP Blood Pressure CI Confidence Interval CKD Chronic Kidney Disease CRF Case Report Form ESRF End-Stage Renal Failure Hb Hemoglobin HD Hemodialysis HIV Human Immunodeficiency Virus IS Iron Sucrose ISS Iron Sucrose Similar IV Intravenous N Sample Size NA Not Available/Missing NBCD Non-biologic Complex Drug PTH Parathyroid Hormone SD Standard Deviation TIBC Total Iron Binding Capacity TSAT Transferrin Saturation Declarations Ethics Approval and consent to participate This study was conducted in accordance with the Declaration of Helsinki and approved by the Medical Research and Ethics Committee (MREC), Malaysia with protocol number: RAN-2020-01 and registration number: NMRR-20-1405-54645 (ISR). MREC, Malaysia has waived the need of informed consent requirement for this retrospective data collected involved de-identified information. Consent For Publication Not applicable. Availability of Data and Material The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing Interests This study does not present any competing of interest for the authors. Funding This study was supported by a grant from Duopharma Biotech Berhad (Malaysia). Author’s Contributions Study conception and design: Gan CC, Lim SK Data collection: Mansor NAN Data analysis and interpretation: Gan CC, Lim SK, Mansor NAN Drafting of manuscript: Gan CC Critical revision: Gan CC, Lim SK, Mansor NAN All authors have read and approved the final manuscript. Acknowledgements We thank Professor Abdul Halim bin Abdul Gafor, Associate Professor Kok Peng Ng, Dr. Tee Chau Keng, Dr. Li Han Lim, and all the dialysis centre staffs involved in providing research information. Authors' information (optional) Not applicable. References Babitt JL, Lin HY. Mechanisms of anemia in CKD. J Am Soc Nephrol. 2012;23(10):1631-1634. Kdoqi, National Kidney F. KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease. Am J Kidney Dis. 2006;47(5 Suppl 3):S11-145. Roger SD. Practical considerations for iron therapy in the management of anemia in patients with chronic kidney disease. Clin Kidney J. 2017;10(Suppl 1):i9-i15. Crommelin DJ, Shah VP, Klebovich I, et al. The similarity question for biologicals and non-biological complex drugs. Eur J Pharm Sci. 2015;76:10-17. Martin-Malo A, Borchard G, Fluhmann B, Mori C, Silverberg D, Jankowska EA. Differences between intravenous iron products: focus on the treatment of iron deficiency in chronic heart failure patients. ESC Heart Fail. 2019;6(2):241-253. Barot BS, Parejiya PB, Mehta DM, Shelat PK, Shah GB. Physicochemical and structural characterization of iron-sucrose formulations: a comparative study. Pharm Dev Technol. 2014;19(5):513-520. Danielson BG. Structure, chemistry, and pharmacokinetics of intravenous iron agents. J Am Soc Nephrol. 2004;15 Suppl 2:S93-98. Geisser P, Burckhardt S. The pharmacokinetics and pharmacodynamics of iron preparations. Pharmaceutics. 2011;3(1):12-33. Wang W, Knovich MA, Coffman LG, Torti FM, Torti SV. Serum ferritin: Past, present, and future. Biochim Biophys Acta. 2010;1800(8):760-769. Wish JB. Assessing Iron Status: Beyond Serum Ferritin and Transferrin Saturation. Clinical Journal of the American Society of Nephrology. 2006;1(Supplement 1):S4-S8. Bonafont X, Bock A, Carter D, et al. A meta-analysis of the relative doses of erythropoiesis-stimulating agents in patients undergoing dialysis. NDT Plus. 2009;2(5):347-353. Jordan J, Breckles J, Leung V, Hopkins M, Battistella M. Conversion from epoetin alfa to darbepoetin alfa: effects on patients' hemoglobin and costs to canadian dialysis centres. Can J Hosp Pharm. 2012;65(6):443-449. Orazi E. [Switch from Darbepoetin-alpha to Epoetin-alpha: cost and efficacy comparison for haemodialytic patients over one year follow-up in a single centre]. G Ital Nefrol. 2008;25(2):223-226. Charytan C, Levin N, Al-Saloum M, Hafeez T, Gagnon S, Van Wyck DB. Efficacy and safety of iron sucrose for iron deficiency in patients with dialysis-associated anemia: North American clinical trial. Am J Kidney Dis. 2001;37(2):300-307. Li H, Wang SX. Intravenous iron sucrose in Chinese hemodialysis patients with renal anemia. Blood Purif. 2008;26(2):151-156. US FDA. Prescribing Information - Venofer. 2017. Aronoff GR, Bennett WM, Blumenthal S, Charytan C, Pennell JP, Reed J, Rothstein M, Strom J, Wolfe A, Van WD, Yee J. Iron sucrose in hemodialysis patients: Safety of replacement and maintenance regimens. Kidney International. 2004; 66(3):1193–1198. doi:10.1111/j.1523-1755.2004.00872.x Shepshelovich D, Rozen-Zvi B, Avni T, Gafter U, Gafter-Gvili A. Intravenous Versus Oral Iron Supplementation for the Treatment of Anemia in CKD: An Updated Systematic Review and Meta-analysis. Am J Kidney Dis. 2016 Nov;68(5):677-690.doi:10.1053/j.ajkd.2016.04.018. Epub 2016 Jun 16. PMID: 27321965. Critchley J, Dundar Y. Adverse events associated with intravenous iron infusion (low-molecular-weight iron dextran and iron sucrose): a systematic review. Transfusion Alternatives in Transfusion Medicine. 2007;9(1):8-36. Additional Declarations No competing interests reported. Supplementary Files Supplementary.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2057589","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":140187460,"identity":"96e9fb30-335e-45d6-a893-3ac52b89acc8","order_by":0,"name":"Chye Chung Gan","email":"","orcid":"","institution":"Department of Medicine, Faculty of Medicine, University of Malaya, Jalan University 50603 Kuala Lumpur","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Chye","middleName":"Chung","lastName":"Gan","suffix":""},{"id":140187461,"identity":"3e09967b-cfbb-41d9-9ce0-beb2c501e108","order_by":1,"name":"Nurul Azwani Nadia Mansor","email":"","orcid":"","institution":"IQVIA Asia Pacific, Real-world insights","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Nurul","middleName":"Azwani Nadia","lastName":"Mansor","suffix":""},{"id":140187462,"identity":"6483a5bf-b476-49f4-aa48-84ebc86ad115","order_by":2,"name":"Soo Kun Lim","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAtklEQVRIiWNgGAWjYBACPmYGBsaGCiiPhxgtbGAtZ0jSAsSMjW0kaWHnTv44c97haN32A4wP3rYxRBscIOgw3m2SG7cdzt12JoHZcG4bQ+4GYrQwPgRpucHAJs1LpJbNHx/OAWth/02slg2SGxsgtjATq2Wb5Ixj6UC/JDZLzjknkTuTkBZ+/rObP/bUWOduO3744Ic3ZTa5fYS0IAHGBiAhwaBAghYokG8gWcsoGAWjYBQMcwAA+RhD2WETdZYAAAAASUVORK5CYII=","orcid":"","institution":"Department of Medicine, Faculty of Medicine, University of Malaya, Jalan University 50603 Kuala Lumpur","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Soo","middleName":"Kun","lastName":"Lim","suffix":""}],"badges":[],"createdAt":"2022-09-12 16:29:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2057589/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2057589/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":27288250,"identity":"5b2f3fcf-cb11-47c1-b8cb-3fb255c5a8a2","added_by":"auto","created_at":"2022-10-03 18:22:01","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":91002,"visible":true,"origin":"","legend":"\u003cp\u003eIllustration of study design\u0026nbsp;IS, Iron Sucrose; ISS, Iron Sucrose Similar, Rx, Medical prescription.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-2057589/v1/8f75c77b7ade3c1f344675df.png"},{"id":27288459,"identity":"2696cc51-58a6-449c-9044-90af7ff0826d","added_by":"auto","created_at":"2022-10-03 18:27:01","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":48030,"visible":true,"origin":"","legend":"\u003cp\u003eStudy flowchart illustrating subject screening to final analysis\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-2057589/v1/386fe2ff7ad4b0895ee9e564.png"},{"id":28749265,"identity":"90a71c70-1948-4689-bf0c-08ab40920054","added_by":"auto","created_at":"2022-11-07 14:00:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1047103,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2057589/v1/99814be3-f66c-43ac-84d2-215febe13cd0.pdf"},{"id":27288252,"identity":"dd8d877b-6be6-4fdd-aa98-f2b70a483e5a","added_by":"auto","created_at":"2022-10-03 18:22:01","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":43481,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementary.docx","url":"https://assets-eu.researchsquare.com/files/rs-2057589/v1/1817fbbd4d786702facbe307.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"The effect of iron (III) hydroxide sucrose complex (Ranofer) and other iron preparations on body iron store in long term hemodialysis patients – A retrospective cohort study","fulltext":[{"header":"Background","content":"\u003cp\u003eIron deficiency is a significant contributor to renal anemia, particularly in hemodialysis (HD) population. The causes are often multifactorial but mainly due to increased iron demand due to the use of erythropoietin stimulating agents (ESAs) and blood loss.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e Anemia in chronic kidney disease (CKD) is correlated with increased cardiovascular disease, cognitive impairment, hospital admissions, mortality, and reduced quality of life.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIntravenous (IV) iron supplementation is an important element in the treatment landscape of anemia management among the HD patients.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e Iron carbohydrate preparations are one of the non-biological complex drugs (NBCD). The NBCDs is expressed as (1) consisting of a complex multitude of closely related structures; (2) the entire multitude is the active pharmaceutical ingredient; (3) the properties cannot be fully described by physicochemical analysis and (4) the consistent, tightly regulated manufacturing process is fundamental to reproduce the product.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e The crucial role of iron therapy in a variety of clinical conditions has led to the advancement and introduction of new iron carbohydrate complexes (e.g. ferric carboxymaltose) and iron sucrose similar (ISS) preparations.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eISS has been marketed under the supposition that they are identical to the originator iron sucrose (IS). However, reproducing the physicochemical identity of IS is challenging.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e Achieving therapeutic interchangeability with the originator is challenging. IV iron formulations take the form of iron carbohydrate complexes in which an iron-containing mineral core is bounded by a carbohydrate ligand for stability. The pharmacologic and biologic properties of the complex are influenced by the different sizes and structures of the mineral core and the carbohydrate shell.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e The degree of stability of iron carbohydrate complexes is critical. Weakly bounded iron may dissociate from the complex and catalyze the generation of reactive oxygen species.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e Stability is highly reliant on the manufacturing method.\u003c/p\u003e \u003cp\u003eSupporting evidence that shows pharmaceutical equivalence for ISS or other iron preparations based on comparable physicochemical properties may not be adequate for NBCDs. This is because they cannot be fully characterized from a physicochemical perspective. In this study, we aim to assess the iron status changes of HD patients who have been initiated on IV iron (III) hydroxide sucrose complex (Ranofer) and other IV iron preparations (non-Ranofer) under real-world clinical settings over a six-month observation period. Besides, we would like to assess the safety profile and the hemoglobin level changes in patients given IV Ranofer and non-Ranofer.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003eThis was a retrospective cohort study that analyzed the effectiveness and safety profiles of Ranofer (IV iron-(III)-hydroxide sucrose complex) and non-Ranofer [Venofer, iron-(III)-hydroxide sucrose complex; Avofer, iron-(III)-hydroxide sucrose complex; Cosmofer, iron-(III)-hydroxide dextran complex] on body iron store in ESKD patients undergoing long term hemodialysis from 11 different dialysis centers within the state of Selangor, Malaysia from January 2017 to August 2020.\u003c/p\u003e \u003cp\u003ePatients were identified from the medical records and included in the study if they met the inclusion and exclusion criteria. The study collected information on demographics, clinical data, comorbidities, hospitalization, and procedure history, within one month before baseline. The safety outcome measures included the history of any of the following symptoms, i.e., hypotension, muscle cramps, headache, and nausea observed during six months from baseline. The date of the treatment initiation was considered as the \u0026ldquo;baseline\u0026rdquo;.\u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e below illustrates the study design described above:\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003ePoint #1 refers to the study treatment initiation point where baseline data were collected.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003ePoint #2 refers to the \u0026ldquo;look back\u0026rdquo; period where the pre-treatment outcome variables were collected.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003ePoint #3 refers to the \u0026ldquo;look forward\u0026rdquo; period (6-months after IV iron initiation) where the outcome data (e.g., serum ferritin, transferrin saturation (TSAT), and Hb) were collected along with the study treatment data and time-varying factors (e.g., erythropoietin use).\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eAdult (age\u0026thinsp;\u0026ge;\u0026thinsp;18 years) with ESKD on long-term hemodialysis initiated intravenous iron therapy during the observation periods.\u003c/p\u003e \u003cp\u003eSpecific inclusion and exclusion criteria are listed below.\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eInclusion Criteria\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePatient with ESKD on regular (at least 3 4-hr sessions per week) long-term hemodialysis for at least 6 months.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eInitiated IV Ranofer or any other IV iron preparations during the determined study period.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePersisted on the (respective) iron formulation for at least 5 consecutive doses.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eHb\u0026thinsp;\u0026lt;\u0026thinsp;12 g/dL, TSAT\u0026thinsp;\u0026le;\u0026thinsp;30% and serum ferritin\u0026thinsp;\u0026le;\u0026thinsp;800ng/mL within one month prior to treatment initiation.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eWith at least one laboratory result available (within six months post-therapy initiation) indicating the post-therapy iron store level.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eExclusion Criteria\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eThe patient was contraindicated for iron therapy.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eThe patient had received blood transfusion one month before or after the initiation of iron therapy.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePatient with known underlying hematological disorder other than iron deficiency anemia (documented within the period of observation).\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePatient with diagnosed retroviral disease (HIV).\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eExposure\u003c/h2\u003e \u003cp\u003eThe exposure groups of this observational study are as follow:\u003c/p\u003e \u003cp\u003eRanofer exposure group was defined as subjects (fulfilling all inclusion and exclusion criteria listed above) who have initiated IV Ranofer during the defined observation period. Non-Ranofer exposure group was defined as subjects (fulfilling all inclusion and exclusion criteria listed above) who have initiated any IV iron preparations (other than Ranofer) during the defined observation period.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eTreatments and evaluations\u003c/h2\u003e \u003cp\u003eBelow is a general description of the treatment and primary study endpoints (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTreatment under investigation and primary study endpoints CKD, Chronic kidney disease; IV, Intravenous.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTreatment under investigation\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntravenous iron sucrose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReplacement of iron stores found in hemoglobin, myoglobin, and enzymes; Indicated for the treatment of iron deficiency anemia associated with chronic kidney disease. Hemodialysis-dependent CKD: 100 mg elemental iron IV (injection or infusion over 2\u0026ndash;5 min) per dialysis session not to exceed a total cumulative dose of 1000 mg divided into 3 doses/week\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eEvaluation for primary study endpoints\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1. Serum ferritin\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFerritin is the cellular storage protein for iron. It is present in small concentrations in blood, and the serum ferritin concentration normally correlates well with total-body iron stores, making its measurement important in the diagnosis of disorders of iron metabolism.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2. Transferrin saturation (TSAT)\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe TSAT is the serum iron divided by the total iron-binding capacity (TIBC), which corresponds to circulating iron. The TIBC reflects transferrin, the protein to which virtually all iron in the blood is bound. The K/DOQI workgroups have determined that absolute iron deficiency, the absence or near absence of stainable iron in the bone marrow, correlates with TSAT\u0026thinsp;\u0026lt;\u0026thinsp;20% and that there is a risk for iron overload when the TSAT exceeds 50%. These also are opinion-based and not evidence-based guidelines.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cp\u003eCKD, Chronic kidney disease; IV, Intravenous.\u003c/p\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eEndpoints\u003c/h2\u003e \u003cp\u003ePrimary:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eTreatment success \u0026ndash; defined as an improvement of serum ferritin of more than 100 microgram/L (highest recorded point) and an improvement of TSAT of more than 20% from baseline to the highest recorded point.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003eSecondary:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eAll-cause mortality within the six months of the defined observation period\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eAll-cause hospitalization within the six months of the defined observation period\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eDocumented adverse event-related symptoms on a medical chart, including hypotension, muscle cramps, headache, nausea, rash(es) and/or itchiness, wheezing and/or shortness of breath, swelling of the face, tongue, or throat.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003eExploratory:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eAbsolute and relative serum hemoglobin improvement from baseline to:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ehighest recorded point post-intervention.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003elast recorded point within the six-month defined observation period.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eData management\u003c/h2\u003e \u003cp\u003eA standardized paper-based Case-Report-Form (CRF) was developed and used to ensure that all data are collected in a standardized and consistent manner. Data on all the listed study variables, abstracted from the medical charts of each eligible study subject. Information not available in the medical charts were considered as missing and be coded as \u0026ldquo;NA\u0026rdquo;. Each eligible subject was prepared with one study-specific case folder that contained all the required CRFs. No identifying information was captured within those CRFs that required electronic transmission; only a unique ID was made available at the study sites in case reidentification is required for any study and non-study-related purpose. Decisions to reidentify the study subject are at the discretion of the participating investigators taking charge of the specific dialysis center.\u003c/p\u003e \u003cp\u003e The received CRFs provided by the study sites underwent an initial screening process for quality checks. This is to ensure that the CRFs received are of adequate quality for the subsequent data entry purpose. The qualities for assessment are for instance range, missingness, etc. The data from paper CRF were entered into the EpiCollect5 database used for storing the study data. CRFs not meeting the required quality standards were returned to the study sites with a specific query raised to the site's study coordinator. All the queries and responses were documented in a log file.\u003c/p\u003e \u003cp\u003eDuring the data entry process, a regular review of the study dataset was conducted once in the mid-phase of the study (approaching half of the target study size) and once at the end of the study before finalizing the study dataset (Database lock). Data review at this stage was intended to identify potential data errors not captured during the initial screening process e.g., outliers, free texts, etc.\u003c/p\u003e \u003cp\u003eNo source document verification was conducted for this study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical methods\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed using R Version 3.5.2. The statistical results were displayed using tables, listings, and/or graphs.\u003c/p\u003e \u003cp\u003eFor univariate descriptive analysis, all categorical variables were present with the following summary measures:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eFrequency (number of cases [n]) and\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003ePercentage (%)\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eFor continuous variables, the following summary measures were computed:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eMean, Standard deviation (SD),\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eMedian, Interquartile range (IQR) and\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eFor bivariate descriptive analyses, all variables were presented using the same set of descriptive measures described above. All descriptive analyses were performed using the exposure group as the bivariate factor. All descriptive summaries stratified by the exposure group were tested for their statistical difference using chi-square for nominal variables, ANOVA test for parametric continuous variables, and Mann-Whitney U test or Kruskal Wallis test for non-parametric variables without adjustment of multiple testing. When the variables have two levels, paired sample t-test for parametric variables and Wilcoxon test for non-parametric variables were used.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003ePrimary Analyses\u003c/h2\u003e \u003cp\u003eThe treatment success was computed as Iron Replacement Achieved, IRA:\u003cdiv id=\"Equa\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equa\" name=\"EquationSource\"\u003e\n$$IRA=\\frac{Number of cases achieving the defined criteria of iron repletion}{Total number of cases}$$\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eTreatment success was calculated for the overall cohort and stratified by the exposure group (i.e. Ranofer group and non-Ranofer group). A crude comparison of the treatment success was made and the difference between the two stratums was tested for statistical significance using the chi-square test.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eSecondary Analyses\u003c/h2\u003e \u003cp\u003eAll secondary endpoints were summarized with the following measures:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eFrequency (n) for the overall cohort, and stratified by the exposure variable (i.e. Ranofer vs. non-Ranofer)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003ePercentage/proportion for the overall cohort, and stratified by the exposure variable\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eCrude comparisons between the exposure strata were performed using the chi-square test.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eExploratory Analyses\u003c/h2\u003e \u003cp\u003eThe below list of statistical summary measures for this endpoint and objective was prepared for all the recordings of Hb during the observation period:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eMean \u0026amp; standard deviation (SD), and\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eMedian \u0026amp; interquartile range (IQR)\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eComparisons were made between the Ranofer group vs. non-Ranofer within each recording period (i.e. baseline reading, 2nd reading, 3rd reading, and all subsequent reading where applicable). ANOVA test, Mann-Whitney U test, or Kruskal Wallis test was used to examine the probability of the two mean/distribution being similar. A two-sided p-value of \u0026le;\u0026thinsp;0.05 will be considered as a statistically significant difference between the two comparators.\u003c/p\u003e \u003cp\u003eThe hemoglobin change from baseline was computed as per below:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eFor absolute Hb change from baseline to the highest recorded point post-intervention or last recorded point within the six-month defined observation period, the following formula will be used:\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003cdiv id=\"Equb\" class=\"Equation\"\u003e \u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equb\" name=\"EquationSource\"\u003e\n$$Absolute Hb change=(highest recorded value or last recorded value-baseline value)$$\u003c/div\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eFor relative Hb change from baseline to the highest recorded point post-intervention or last recorded point within the six-month defined observation period, the following formula was used:\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003cdiv id=\"Equc\" class=\"Equation\"\u003e \u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equc\" name=\"EquationSource\"\u003e\n$$Relative Hb change=\\frac{(highest recorded value or last recorded value-baseline value)}{baseline value}$$\u003c/div\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003eSimilarly, comparisons were made between the Ranofer group vs. the non-Ranofer group for the above exploratory endpoints. ANOVA test, Mann-Whitney U test, or Kruskal Wallis test was used to examine the probability of the two mean/distribution being similar. A two-sided p-value of \u0026le;\u0026thinsp;0.05 was considered as a statistically significant difference between the two comparators.\u003c/p\u003e \u003cp\u003eA linear regression model was used to examine the relationship between the exposure variable (Ranofer vs. non-Ranofer) in the primary and exploratory outcome measure (achievement of iron repletion and change of Hb from baseline). A set of bivariate regression analyses was performed for the below baseline variables in addition to the exposure variable: age, gender, ethnicity, BMI, smoking status, Charlson comorbid score, baseline BP, baseline ferritin, baseline TSAT, baseline Hb, duration of dialysis, IV iron cumulative dose, EPO cumulative dose, baseline serum albumin (g/dL), baseline serum PTH (pg/mL), baseline Kt/V, and history of hospitalization.\u003c/p\u003e \u003cp\u003eAll variables with a p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.1 detected in the bivariate regression model were further considered for multivariate regression analysis. The two-sided significant level of 0.05 will be used to reject the null hypothesis.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eDuring the study period from January 2017 to August 2020, a total of 291 subjects were screened and we obtained a dataset containing 220 complete subject cases for the intended analysis. Of the 220 datasets from the primary analysis, one subject was excluded from exploratory analysis due to missing outcome data. The subjects' screening process is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eDemographic and baseline characteristics\u003c/h2\u003e \u003cp\u003eMost of the patients were male (57.70%) with the mean age of 55.24\u0026thinsp;\u0026plusmn;\u0026thinsp;14.00 years and Malaysian Chinese descendants made up 40.5% of study subjects followed by 37.7% Malay, 21.4% Indian, and 0.5% others. The median BMI was 24.08 with interquartile-range (IQR) of 21.11\u0026ndash;27.32 kg/m\u003csup\u003e2\u003c/sup\u003e. Median dialysis vintage was 3.00 years with IQR of 1.00\u0026ndash;5.00 years and the median Kt/V was 1.30 with IQR of 1.10\u0026ndash;1.50, in which 150 (72.1%) of the subjects achieved Kt/V of \u0026ge;\u0026thinsp;1.2. The most common dialysis access was AV-Fistula (85.5%), followed by catheter (13.1%) and AV-Graft (1.4%).\u003c/p\u003e \u003cp\u003eCharlson index score recorded a median of 2 with IQR of 1\u0026ndash;3. Of the total subjects, 152 (69.1%) have hypertension, 75 (34.1%) have diabetes treated with insulin, 6 (2.7%) have a history of myocardial infarction, 4 (1.8%) has a stroke with a deficit, 6 (2.7%) have a history of hospitalization 1 month before study, and 1 (0.5%) has surgical procedure 1 month before the study. The difference in the baseline characteristics between the Ranofer group and the non-Ranofer group was statistically insignificant (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e: Baseline characteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll Subjects\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;220)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRanofer\u0026reg;\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;108)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNon-Ranofer\u0026reg;\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;112)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDemographic\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge \u0026ndash; years\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55.24\u0026thinsp;\u0026plusmn;\u0026thinsp;14.00\u003c/p\u003e \u003cp\u003e(53.83, 58.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54.17\u0026thinsp;\u0026plusmn;\u0026thinsp;14.89\u003c/p\u003e \u003cp\u003e(51.33, 57.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e56.28\u0026thinsp;\u0026plusmn;\u0026thinsp;13.07\u003c/p\u003e \u003cp\u003e(53.38, 57.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.265\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGender \u0026ndash; n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e127 (57.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63 (58.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e64 (57.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.858\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e93 (42.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45 (41.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48 (42.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEthnicity \u0026ndash; n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMalay\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e83 (37.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44 (40.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39 (34.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChinese\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e89 (40.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39 (36.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50 (44.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.427\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47 (21.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (23.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22 (19.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (0.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHeight \u0026ndash; cm\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e162.00\u003c/p\u003e \u003cp\u003e(156.00, 168.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e162.00\u003c/p\u003e \u003cp\u003e(156.00, 168.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e163.00\u003c/p\u003e \u003cp\u003e(156.00, 167.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.969\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMissing data\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (10%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (19%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (0.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBody weight \u0026ndash; kg\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63.00\u003c/p\u003e \u003cp\u003e(53.33, 74.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63.05\u003c/p\u003e \u003cp\u003e(55.00, 74.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61.70\u003c/p\u003e \u003cp\u003e(52.50, 74.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.659\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBMI \u0026ndash; kg/m\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.08\u003c/p\u003e \u003cp\u003e(21.11, 27.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.09\u003c/p\u003e \u003cp\u003e(22.00, 27.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23.73\u003c/p\u003e \u003cp\u003e(20.74, 27.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.568\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMissing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (10%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (19%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (0.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClinical characteristics\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDialysis access\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAV-Fistula\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e188 (85.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e92 (85.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e96 (85.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.827\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAV-Graft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (1.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (1.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (0.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCatheter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (13.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (13.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (13.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHD vintage, year(s)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.00 (1.00, 5.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.00 (1.00, 5.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.00 (1.00, 5.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.858\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHD vintage category\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt; 5 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e154 (70.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77 (71.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e77 (68.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.878\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u0026ndash;10 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48 (21.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (20.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26 (23.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt; 10 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (8.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (8.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (8.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBaseline SBP, mmHg\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e147.94\u0026thinsp;\u0026plusmn;\u0026thinsp;24.61 (144.67, 151.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e148.05\u0026thinsp;\u0026plusmn;\u0026thinsp;23.90 (143.49, 152.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e147.83\u0026thinsp;\u0026plusmn;\u0026thinsp;25.38 (143.08, 152.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.948\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBaseline DBP, mmHg\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e77.63\u0026thinsp;\u0026plusmn;\u0026thinsp;14.27 (75.736, 79.528)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e78.61\u0026thinsp;\u0026plusmn;\u0026thinsp;13.38 (76.058, 81.164)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e76.69\u0026thinsp;\u0026plusmn;\u0026thinsp;15.07 (73.865, 79.510)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.319\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eComorbidities\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCharlson Index Score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.00 (1.00, 3.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.00 (1.00, 3.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.00 (1.00, 2.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.330\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHypertension\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e152 (69.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80 (74.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e72 (64.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.116\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDM treated with insulin\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75 (34.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38 (35.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37 (33.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.737\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHistory of MI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (2.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (3.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (1.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.383\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eStroke with deficit\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (1.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (2.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (0.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.296\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHistory of hospitalization one month prior IVIS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (2.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (4.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (0.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.089\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHistory of surgical procedure one month prior IVIS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.307\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBaseline laboratory results\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMedian baseline serum ferritin, (ng/mL), IQR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e278.50\u003c/p\u003e \u003cp\u003e(147.25, 457.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e268.00\u003c/p\u003e \u003cp\u003e(137.75, 464.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e284.00\u003c/p\u003e \u003cp\u003e(153.75, 453.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.545\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBaseline serum ferritin category\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 (14.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (20.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (8.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e188 (85.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e86 (79.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e102 (91.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMedian baseline TSAT, IQR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19.00\u003c/p\u003e \u003cp\u003e(15.00, 23.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18.00\u003c/p\u003e \u003cp\u003e(15.00, 24.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19.00\u003c/p\u003e \u003cp\u003e(14.00, 23.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.623\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBaseline TSAT category\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.964\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e128 (58.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63 (58.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e65 (58.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt; 20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e92 (41.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45 (41.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47 (42.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMedian baseline Hb (g/dL), IQR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.70\u003c/p\u003e \u003cp\u003e(8.80, 10.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.80\u003c/p\u003e \u003cp\u003e(9.10, 10.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.70\u003c/p\u003e \u003cp\u003e(8.50, 10.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.195\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBaseline Hb category\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.964\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e92 (41.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45 (41.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47 (42.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e128 (58.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63 (58.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e65 (58.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMedian baseline serum albumin (g/dL), IQR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40.00\u003c/p\u003e \u003cp\u003e(38.00, 42.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41.00\u003c/p\u003e \u003cp\u003e(38.00, 42.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40.00\u003c/p\u003e \u003cp\u003e(37.75, 42.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.238\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMedian baseline serum PTH (pmol/L), IQR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.00\u003c/p\u003e \u003cp\u003e(6.00, 40.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.00\u003c/p\u003e \u003cp\u003e(13.50, 60.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.00\u003c/p\u003e \u003cp\u003e(4.00, 27.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMissing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (10.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (15.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (6.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBaseline serum PTH category\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e88 (44.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (27.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e63 (60.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e150\u0026ndash;300\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44 (22.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (26.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 (19.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;300\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64 (32.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42 (46.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22 (21.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMissing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (10.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (15.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (6.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMedian baseline Kt/V (mL,min), IQR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.30 (1.10, 1.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.30 (1.10, 1.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.30 (1.20, 1.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.029\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBaseline Kt/V category\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e0.065\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58 (27.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33 (34.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25 (22.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e150 (72.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64 (66.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e86 (77.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMissing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (5.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (10.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (0.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBaseline erythropoietin category\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.979\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e218 (99.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e107 (99.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e111 (99.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (0.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (0.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eBaseline clinical hematology characteristics\u003c/h2\u003e \u003cp\u003eThe median baseline serum ferritin was 278.50 mg/L (IQR 147.25\u0026ndash;457.75) and most subjects had baseline serum ferritin of more than 100 mg/L (85.5%). Meanwhile, the median TSAT at baseline was 19% (IQR 15.00\u0026ndash;23.00). Around 92 (41.8%) subjects had TSAT more than 20% at baseline. The median baseline hemoglobulin level was 9.70 g/dL (IQR of 8.80\u0026ndash;10.60). The result showed that the median baseline serum iPTH was 165.6 pg/mL (IQR 59.7\u0026ndash;376.0) with 142 (72.4%) of the subjects having baseline iPTH of \u0026gt;\u0026thinsp;65 pg/mL. During the study, 218 (99.1%) of the subjects were using erythropoietin. Of all the subjects, 120 (56.1%) used Recormon, 85 (39.7%) used Mircera, 6 (2.8%) used Nesp, 3 (1.4%) used Eprex, and 4 with missing data.\u003c/p\u003e \u003cp\u003eRanofer cohort observed statistically significant differences from non-Ranofer cohort to have more subjects with baseline serum iron of \u0026le;\u0026thinsp;100ng/mL, median Kt/V of \u0026lt;\u0026thinsp;1.2, higher baseline median iPTH, and more subjects in the category with iPTH\u0026thinsp;\u0026gt;\u0026thinsp;65 pg/mL (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003ePrimary Outcomes\u003c/h2\u003e \u003cp\u003eOf all the subjects, 124 (56.4%) achieved the primary outcome of iron repletion. Ranofer group recorded IRA of 56 subjects (51.9%) whereas non-Ranofer group recorded 68 subjects (60.7%) with no statistically significant difference between the two groups, p\u0026thinsp;=\u0026thinsp;0.185 (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eStudy Outcomes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e: Study outcomes\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll Subjects\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;220)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRanofer\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;108)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNon-Ranofer\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;112)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePrimary\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIron repletion achieved\u003c/b\u003e (change in Serum ferritin\u0026thinsp;\u0026gt;\u0026thinsp;100 mg/L and highest recorded TSAT\u0026thinsp;\u0026gt;\u0026thinsp;20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e124 (56.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56 (51.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e68 (60.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.185\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChange in serum ferritin\u0026thinsp;\u0026gt;\u0026thinsp;100 mg/L\u003c/b\u003e (From baseline to highest recorded value)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e159 (72.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75 (69.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e84 (75.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.357\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChange in serum ferritin\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(From baseline to highest recorded value)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e224.50\u003c/p\u003e \u003cp\u003e(93.00, 487.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e215.00\u003c/p\u003e \u003cp\u003e(78.00, 389.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e243.50\u003c/p\u003e \u003cp\u003e(106.75, 505.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.286\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChange TSAT\u0026thinsp;\u0026gt;\u0026thinsp;20%\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(From baseline to highest recorded value)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e160 (72.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75 (69.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e85 (75.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.283\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChange in TSAT\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(From baseline to highest recorded value)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.00\u003c/p\u003e \u003cp\u003e(3.60, 18.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.00\u003c/p\u003e \u003cp\u003e(3.00, 17.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.50\u003c/p\u003e \u003cp\u003e(4.00, 18.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.245\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSecondary\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMortality at the end of the study\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (7.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (5.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (8.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.335\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHypotension episode\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (5.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (10.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (1.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.008*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMuscle cramps\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (2.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (2.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (1.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.622\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHeadache\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (3.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (6.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (0.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.027*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNausea\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (2.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (2.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (1.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.622\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRash(es) and/or itchiness\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.787\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWheezing\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.787\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSwelling of the face, tongue, or throat\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.787\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHistory of hospitalization within 6 months after IVIS initiation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (8.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (13.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (3.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.006*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHistory of surgical procedure 6 months after IVIS initiation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (3.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (4.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (1.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.230\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eExploratory\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAbsolute change in Hb\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(last reading - From baseline to last recorded value)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.90\u003c/p\u003e \u003cp\u003e(0.00, 1.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.80\u003c/p\u003e \u003cp\u003e(-0.15, 1.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003cp\u003e(0.18, 1.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.278\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRelative change in Hb\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(last reading - From baseline to last recorded value)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003cp\u003e(0.00, 0.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003cp\u003e(-0.02, 0.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.10\u003c/p\u003e \u003cp\u003e(0.02, 0.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.234\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHb\u0026thinsp;\u0026ge;\u0026thinsp;10\u003c/b\u003e (last reading)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e157 (71.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e78 (72.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e79 (70.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.698\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eTSAT, Transferrin Saturation; Hb, Hemoglobin; IVIS, Intravenous Iron Sucrose.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe association between biodemographic factors (age, sex, ethnicity, BMI, and smoking status) and clinical findings (duration of dialysis, BP, Charlson Index, serum ferritin, TSAT, IV iron cumulative dose, EPO dose, serum albumin, serum PTH, Kt/V and history of hospitalization) with iron repletion rate were tested in univariate logistic regression (Supplement 1). None of the factors were significantly associated with treatment success except for baseline serum ferritin and baseline TSAT with (OR, 0.998; 95% CI, 0.997\u0026ndash;1.000; p-value\u0026thinsp;=\u0026thinsp;0.030) and (OR, 0.935; 95% CI, 0.893\u0026ndash;0.977; p-value\u0026thinsp;=\u0026thinsp;0.004) respectively.\u003c/p\u003e \u003cp\u003eThese two variables were further tested in multivariate analysis to find out the magnitude of association with exposure variables (IV iron sucrose group \u0026ndash; Ranofer) and treatment success. The odd ratio for baseline ferritin was statistically insignificant (OR, 0.999; 95% CI, 0.997\u0026ndash;1.000; p-value\u0026thinsp;=\u0026thinsp;0.077). The odds ratio for baseline TSAT shown statistically significant (OR, 0.941; 95% CI, 0.898\u0026ndash;0.984; p-value\u0026thinsp;=\u0026thinsp;0.009). This validates that this baseline ferritin is not a potential confounder in the analysis that could affect the results except TSAT (Supplement 1). However, the significance of the OR\u0026thinsp;=\u0026thinsp;0.941 for TSAT remains questionable in the clinical setting.\u003c/p\u003e \u003cp\u003eThe median cumulative IV iron dose within 6-month of the study period was 1000.00 mg for all subjects. The median cumulative dose within 6-month is higher in the Ranofer group than the non-Ranofer group, 1000.00 mg (IQR 500.00\u0026ndash;1300.00) and 600.00 mg (IQR 500.00\u0026ndash;1000.00) respectively and it was a statistically significant difference (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). However, the association between IRA and IV iron cumulative dose was not statistically significant in univariate analysis (Supplement 1).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eIron and EPO administration\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e: Iron and EPO administration\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll Subjects\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;220)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRanofer\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;108)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNon-Ranofer\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;112)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIV Iron administration\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCumulative dose (mg)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1000.00\u003c/p\u003e \u003cp\u003e(500.00, 1000.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1000.00 (500.00, 1300.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e600.00\u003c/p\u003e \u003cp\u003e(500.00, 1000.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDays between administration\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.00\u003c/p\u003e \u003cp\u003e(7.00, 14.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.00\u003c/p\u003e \u003cp\u003e(7.00, 11.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.00\u003c/p\u003e \u003cp\u003e(7.00, 15.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.333\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFrequency of IVIS per administration (per month)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.00 (2.00, 3.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.00 (2.00, 3.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.00 (2.00, 3.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.102\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eErythropoietin administration\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eStarting dose - IU per week\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6000.00\u003c/p\u003e \u003cp\u003e(4000.00, 8000.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7500.00 (4000.00, 9900.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6000.00 (4000.00, 7500.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.125\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAverage dose - IU per week\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4472.22\u003c/p\u003e \u003cp\u003e(2613.91, 6616.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4458.33 (2500.00, 6714.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4488.89 (2901.82, 6400.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.641\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eIV, Intravenous; IVIS, Intravenous Iron Sucrose; IU, International Unit,\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eIS, Iron Sucrose; ISS, Iron Sucrose Similar, Rx, Medical prescription.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eMeanwhile, the median dose per week of erythropoietin at baseline was 6000.00 IU/week (IQR 4000.00\u0026ndash;8000.00). Erythropoietin with the unit of mcg was converted to IU using a conversion ratio of 200 IU\u0026thinsp;=\u0026thinsp;1 mcg, based on several published literature.\u003csup\u003e\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e We notice the reduction of median dose per week over the 6-month study period which was 4472.22 IU/week (2613.91\u0026ndash;6616.67). A paired-samples t-test was conducted to compare the starting dose of erythropoietin (IU/week) and the average dose of erythropoietin used over the 6 months (IU/week) in the Ranofer and non-Ranofer group. In the Ranofer group, subjects needed less erythropoietin dosage over the 6-month study period M\u0026thinsp;=\u0026thinsp;6431, SD\u0026thinsp;=\u0026thinsp;4789.26; t(106)\u0026thinsp;=\u0026thinsp;6.403, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 after IV Iron infusion, as compared to baseline M\u0026thinsp;=\u0026thinsp;14018.13, SD\u0026thinsp;=\u0026thinsp;13108.03, and this was statistically significant. Similar trend was observed in the non-Ranofer group, where the median erythropoietin dosage over the 6-month study period after IV Iron infusion was M\u0026thinsp;=\u0026thinsp;5904.12, SD\u0026thinsp;=\u0026thinsp;4081.97; t(110)\u0026thinsp;=\u0026thinsp;3.389, p\u0026thinsp;=\u0026thinsp;0.001, as compared to baseline of M\u0026thinsp;=\u0026thinsp;9720.72, SD\u0026thinsp;=\u0026thinsp;13749.16, p\u0026thinsp;=\u0026thinsp;0.001. The median dose per week over the 6-month study period in the Ranofer group did not differ from the non-Ranofer group, i.e., 4458.33 IU/week (IQR 2500.00\u0026ndash;6714.29) and 4488.89 IU/week (IQR 2901.82\u0026ndash;6400.00), respectively with p\u0026thinsp;=\u0026thinsp;0.641 (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eSecondary Outcomes\u003c/h2\u003e \u003cp\u003eOf the 220 patients included in safety analyses, 204 patients (92.7%) were reported to be alive at the end of the study. The most reported adverse events (AE) were hypotension (13 subjects, 5.9%), headache (8 subjects, 3.6%), nausea (5 subjects, 2.3%), and muscle cramps (5 subjects, 2.3%). Further analysis showed that subjects in Ranofer reported higher number of these AEs compared to other IV iron group; hypotension 11 (10.2%) versus 2 (1.8%); headache 7 (6.4%) versus 1 (0.9%); nausea 3 (2.8%) versus 2 (1.8%) and muscle cramps 3 (2.8%) versus 2 (1.8%), respectively (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFurthermore, 15 subjects out of 109 (13.9%) in the Ranofer group reported a history of hospitalization within 6-month post IV iron sucrose administration compared to the non-Ranofer group which recorded 4 subjects (3.6%) out of 112. (p\u0026thinsp;=\u0026thinsp;0.006).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eExploratory Outcomes\u003c/h2\u003e \u003cp\u003eThe median absolute changes in Hb level from baseline to last recorded value over 6-month of the study observation period was slightly lower in Ranofer 0.80 g/dL (IQR \u0026minus;\u0026thinsp;0.15\u0026ndash;1.90) compared to non-Ranofer group 1.00 g/dL (IQR 0.18\u0026ndash;1.83), however, it was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.278). The same trend can be seen for median absolute change in Hb level from baseline to highest recorded value; i.e. Ranofer, 1.10 g/dL (IQR 0.3\u0026ndash;2.1) and non-Ranofer, 1.30 g/dL (IQR 0.58\u0026ndash;2.53) respectively (p\u0026thinsp;=\u0026thinsp;0.318).\u003c/p\u003e \u003cp\u003eMeanwhile, the median relative changes in Hb level from baseline to either last or highest recorded value over 6-month study period also displayed similar inclination, where non-Ranofer recorded slightly higher median changes 0.10 g/dL (IQR 0.02\u0026ndash;0.23) and 0.13 g/dL (IQR 0.06\u0026ndash;0.29 respectively; compared to Ranofer group 0.07 g/dL (IQR \u0026minus;\u0026thinsp;0.02\u0026ndash;0.21) and 0.11 g/dL (IQR 0.03\u0026ndash;021) respectively which was statistically insignificant (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOf 219 subjects included in exploratory analysis, 157 (71.7%) achieved Hb\u0026thinsp;\u0026ge;\u0026thinsp;10 g/dL at the last recording over 6-month of the study observation period. The breakdown by Ranofer and non-Ranofer group can be seen in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e with no statistically significant difference between the 2 groups.\u003c/p\u003e \u003cp\u003eAssociation analysis of the Hb changes with biodemographic factors (age, sex, ethnicity, BMI, and smoking status) and clinical findings (duration of dialysis, BP, Charlson Index, serum ferritin, TSAT, IV iron dose, EPO dose, serum albumin, serum PTH, Kt/V, and history of hospitalization) showed none of the factors were significantly associated when tested in univariate linear regression apart from baseline serum albumin and baseline Hb (Supplement 2.1 and 2.2). These variables were further tested in multivariate analysis to find out the magnitude of association with exposure variables (IV iron sucrose group \u0026ndash; Ranofer) and Hb changes (absolute and relative). The beta coefficient and p-value remain comparable with no bigger changes (Supplement 2.1 and 2.2) compared to univariate analysis. Hence, further validates that this variable is not potentially confounding in the analysis that could affect the results.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study was designed to compare the efficacy of Ranofer with other intravenous iron preparations (non-Ranofer) retrospectively. The current data suggest that Ranofer has comparable efficacy compared to other commonly used IV iron brands in Malaysia (Venofer, Avofer, and Cosmofer). Six-month post-baseline, around half (56/108, 51.9%) of the subjects in the Ranofer group achieved the defined iron repletion status. Within the non-Ranofer group, 60.7% (68/112) achieved the defined iron repletion status. These results showed that Ranofer can offer comparable efficacy to other IV iron preparation available in the market. Even though the Ranofer group showed a higher cumulative dose of IV iron administration, this factor does not confound the iron replacement achievement in univariate analysis (Supplement 1). Besides, the IV Ranofer group was able to show a similar reduction in erythropoietin requirements after IV iron administration compared to the IV non-Ranofer group (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Our exploratory analysis which evaluated the changes of Hb status after 6 months of IV Ranofer therapy suggested similar results. Around 78 (72.9%) in the Ranofer group and 79 (70.5%) in the non-Ranofer group attained Hb\u0026thinsp;\u0026ge;\u0026thinsp;10 g/dL (at last recording value over the 6-month study period).\u003c/p\u003e \u003cp\u003eThese observations are consistent with previous studies of iron sucrose. Charytan et al 2001 reported that after 10 doses of iron sucrose injection, TSAT, serum ferritin, and Hb values increased significantly in patients with dialysis-dependency.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e Fifty-eight patients have an improvement in iron status with TSAT\u0026thinsp;\u0026gt;\u0026thinsp;20% and serum ferritin\u0026thinsp;\u0026gt;\u0026thinsp;300 ng/mL and 60 patients were able to attain the target Hb level of 11.0 g/dL.\u003csup\u003e16\u003c/sup\u003e Similarly, a study in the Chinese population that explored the efficacy and safety of IV iron sucrose also disclosed that serum ferritin and TSAT levels also increased significantly after 8 and 12 weeks of treatment suggesting that ideal iron status in Chinese hemodialysis patients is TSAT 30\u0026ndash;40% and serum ferritin 200\u0026ndash;500 mg/L.\u003csup\u003e17\u003c/sup\u003e This study also reported that about 45 (64.3%) patients reached full treatment response defined as an increase in Hb\u0026thinsp;\u0026ge;\u0026thinsp;30 g/L.\u003csup\u003e17\u003c/sup\u003e These studies' findings are consistent with current study results which revealed that both IV iron sucrose or other IV iron preparations can produce almost comparable efficacy in serum iron store, TSAT and Hb improvement.\u003c/p\u003e \u003cp\u003eSafety outcomes reported in the current study indicated that hypotension (10.2%) and headache (6.5%) are relatively higher in the Ranofer group compared to the non-Ranofer group (1.8% and 0.9%, respectively). However, based on information from the study of Venofer described in FDA package insert, hypotension and headache were quite prevalent especially in hemodialysis patients, with hypotension and headache reported around 91 (39.4%) and 29 (12.6%), respectively.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e Meanwhile, Charyton et al 2001, stated that 12 (15.6%) patients receiving Venofer reported hypotension during the treatment period.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e Several other studies in iron sucrose preparation and other iron preparations did show similar adverse events.\u003csup\u003e19\u0026ndash;21\u003c/sup\u003e Thus, it is expected that Ranofer would yield similar side effects rates comparable with another iron brand. The difference in the current study possibly arises due to the nature of the retrospective study. In addition, the adverse events were observed throughout the 6 months of the study period and did not occur specifically within 1 week of the administration of the iron preparations. A retrospective study does not provide real-time information compared to a clinical trial. Without sufficiently complete follow-up information on the patients, this may lead to over or underestimation of the rate of adverse events in dialysis centers. With the limitations of the retrospective study, we are not able to draw a conclusion on the cause-effect relationship between IV Iron administration and the adverse events.\u003c/p\u003e \u003cp\u003eThe present study has several limitations related to the study design and data sources. Any observations or conclusions must be interpreted within the limitations of a retrospective study that may have selection bias, missing data, limited generalizability as these data derived from a limited number of dialysis centers around Selangor, and non-causal relationship nature of this study. A richer discussion to confirm these findings may be achieved with further randomized control trials.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe above analyses suggest that Ranofer has similar efficacy compared with other IV iron preparations for ESRD undergoing long-term hemodialysis despite the slight disadvantages of its adverse effect profile. Interpretation of the findings should account for the limitations of a retrospective study discussed above. Further investigation may provide stronger evidence to confirm the findings of this study.\u003c/p\u003e\n"},{"header":"Abbreviations","content":"\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" id=\"Tabb\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAbbreviations\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDescription of abbreviations\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAdverse Event\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBlood Pressure\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eConfidence Interval\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCKD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChronic Kidney Disease\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCRF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCase Report Form\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eESRF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEnd-Stage Renal Failure\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHemoglobin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHemodialysis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHuman Immunodeficiency Virus\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIron Sucrose\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eISS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIron Sucrose Similar\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIntravenous\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSample Size\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNot Available/Missing\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNBCD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNon-biologic Complex Drug\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePTH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eParathyroid Hormone\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStandard Deviation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTIBC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal Iron Binding Capacity\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTSAT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTransferrin Saturation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics Approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the Declaration of Helsinki and approved by the Medical Research and Ethics Committee (MREC), Malaysia with protocol number: RAN-2020-01 and registration number: NMRR-20-1405-54645 (ISR). \u0026nbsp;\u003cstrong\u003eMREC, Malaysia has waived the need of informed consent requirement for this retrospective data collected involved de-identified information.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eConsent For Publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of Data and Material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study does not present any competing of interest for the authors.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by a grant from Duopharma Biotech Berhad (Malaysia).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eAuthor\u0026rsquo;s Contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStudy conception and design: Gan CC, Lim SK\u0026nbsp;\u003cbr\u003e\u0026nbsp;Data collection: Mansor NAN\u003c/p\u003e\n\u003cp\u003eData analysis and interpretation: Gan CC, Lim SK, Mansor NAN\u003c/p\u003e\n\u003cp\u003eDrafting of manuscript: Gan CC\u003c/p\u003e\n\u003cp\u003eCritical revision: Gan CC, Lim SK, Mansor NAN\u003c/p\u003e\n\u003cp\u003eAll authors have read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank Professor Abdul Halim bin Abdul Gafor, Associate Professor Kok Peng Ng, Dr. Tee Chau Keng, Dr. Li Han Lim, and all the dialysis centre staffs involved in providing research information.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eAuthors\u0026apos; information (optional)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBabitt JL, Lin HY. Mechanisms of anemia in CKD. \u003cem\u003eJ Am Soc Nephrol. \u003c/em\u003e2012;23(10):1631-1634.\u003c/li\u003e\n\u003cli\u003eKdoqi, National Kidney F. KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease. \u003cem\u003eAm J Kidney Dis. \u003c/em\u003e2006;47(5 Suppl 3):S11-145.\u003c/li\u003e\n\u003cli\u003eRoger SD. Practical considerations for iron therapy in the management of anemia in patients with chronic kidney disease. \u003cem\u003eClin Kidney J. \u003c/em\u003e2017;10(Suppl 1):i9-i15.\u003c/li\u003e\n\u003cli\u003eCrommelin DJ, Shah VP, Klebovich I, et al. The similarity question for biologicals and non-biological complex drugs. \u003cem\u003eEur J Pharm Sci. \u003c/em\u003e2015;76:10-17.\u003c/li\u003e\n\u003cli\u003eMartin-Malo A, Borchard G, Fluhmann B, Mori C, Silverberg D, Jankowska EA. Differences between intravenous iron products: focus on the treatment of iron deficiency in chronic heart failure patients. \u003cem\u003eESC Heart Fail. \u003c/em\u003e2019;6(2):241-253.\u003c/li\u003e\n\u003cli\u003eBarot BS, Parejiya PB, Mehta DM, Shelat PK, Shah GB. Physicochemical and structural characterization of iron-sucrose formulations: a comparative study. \u003cem\u003ePharm Dev Technol. \u003c/em\u003e2014;19(5):513-520.\u003c/li\u003e\n\u003cli\u003eDanielson BG. Structure, chemistry, and pharmacokinetics of intravenous iron agents. \u003cem\u003eJ Am Soc Nephrol. \u003c/em\u003e2004;15 Suppl 2:S93-98.\u003c/li\u003e\n\u003cli\u003eGeisser P, Burckhardt S. The pharmacokinetics and pharmacodynamics of iron preparations. \u003cem\u003ePharmaceutics. \u003c/em\u003e2011;3(1):12-33.\u003c/li\u003e\n\u003cli\u003eWang W, Knovich MA, Coffman LG, Torti FM, Torti SV. Serum ferritin: Past, present, and future. \u003cem\u003eBiochim Biophys Acta. \u003c/em\u003e2010;1800(8):760-769.\u003c/li\u003e\n\u003cli\u003eWish JB. Assessing Iron Status: Beyond Serum Ferritin and Transferrin Saturation. \u003cem\u003eClinical Journal of the American Society of Nephrology. \u003c/em\u003e2006;1(Supplement 1):S4-S8.\u003c/li\u003e\n\u003cli\u003eBonafont X, Bock A, Carter D, et al. A meta-analysis of the relative doses of erythropoiesis-stimulating agents in patients undergoing dialysis. \u003cem\u003eNDT Plus. \u003c/em\u003e2009;2(5):347-353.\u003c/li\u003e\n\u003cli\u003eJordan J, Breckles J, Leung V, Hopkins M, Battistella M. Conversion from epoetin alfa to darbepoetin alfa: effects on patients\u0026apos; hemoglobin and costs to canadian dialysis centres. \u003cem\u003eCan J Hosp Pharm. \u003c/em\u003e2012;65(6):443-449.\u003c/li\u003e\n\u003cli\u003eOrazi E. [Switch from Darbepoetin-alpha to Epoetin-alpha: cost and efficacy comparison for haemodialytic patients over one year follow-up in a single centre]. \u003cem\u003eG Ital Nefrol. \u003c/em\u003e2008;25(2):223-226.\u003c/li\u003e\n\u003cli\u003eCharytan C, Levin N, Al-Saloum M, Hafeez T, Gagnon S, Van Wyck DB. Efficacy and safety of iron sucrose for iron deficiency in patients with dialysis-associated anemia: North American clinical trial. \u003cem\u003eAm J Kidney Dis. \u003c/em\u003e2001;37(2):300-307.\u003c/li\u003e\n\u003cli\u003eLi H, Wang SX. Intravenous iron sucrose in Chinese hemodialysis patients with renal anemia. \u003cem\u003eBlood Purif. \u003c/em\u003e2008;26(2):151-156.\u003c/li\u003e\n\u003cli\u003eUS FDA. \u003cem\u003ePrescribing Information - Venofer. \u003c/em\u003e2017.\u003c/li\u003e\n\u003cli\u003eAronoff GR, Bennett WM, Blumenthal S, Charytan C, Pennell JP, Reed J, Rothstein M, Strom J, Wolfe A, Van WD, Yee J. Iron sucrose in hemodialysis patients: Safety of replacement and maintenance regimens. Kidney International. 2004; 66(3):1193\u0026ndash;1198. doi:10.1111/j.1523-1755.2004.00872.x \u003c/li\u003e\n\u003cli\u003eShepshelovich D, Rozen-Zvi B, Avni T, Gafter U, Gafter-Gvili A. Intravenous Versus Oral Iron Supplementation for the Treatment of Anemia in CKD: An Updated Systematic Review and Meta-analysis. Am J Kidney Dis. 2016 Nov;68(5):677-690.doi:10.1053/j.ajkd.2016.04.018. Epub 2016 Jun 16. PMID: 27321965.\u003c/li\u003e\n\u003cli\u003eCritchley J, Dundar Y. Adverse events associated with intravenous iron infusion (low-molecular-weight iron dextran and iron sucrose): a systematic review. \u003cem\u003eTransfusion Alternatives in Transfusion Medicine. \u003c/em\u003e2007;9(1):8-36.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Intravenous (IV) iron-(III)-hydroxide-sucrose-complex, iron deficiency anemia, hemodialysis","lastPublishedDoi":"10.21203/rs.3.rs-2057589/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2057589/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e \u003cp\u003eIntravenous iron is important in the management of iron deficiency and renal anemia among hemodialysis patients. Iron sucrose is one of the commonly used iron preparations in Malaysia. Our study objective is to assess the iron status changes in hemodialysis patients who have been initiated on intravenous (IV) iron-(III)-hydroxide-sucrose-complex (Ranofer) and other IV iron preparations (non-Ranofer) under real-world clinical settings over a six-month observation period.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003eA retrospective cohort study was conducted to analyze the effectiveness and safety profiles of IV-Ranofer and IV-non-Ranofer on body iron stores in end-stage kidney disease (ESKD) patients across dialysis centers in Selangor from 01.01.2017 to 31.08.2020. Two-hundred-twenty subjects were included in the final analysis. Clinical response is defined as an improvement on serum ferritin\u0026thinsp;\u0026gt;\u0026thinsp;100 microgram/L and TSAT\u0026thinsp;\u0026gt;\u0026thinsp;20% at any point within the period of 6-months.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003eOf the 220-subjects, 124 (56.4%) achieved clinical response, in which the Ranofer group recorded 56 (51.9%) and the non-Ranofer group recorded 68 (60.7%) respectively, with no difference in between groups (p\u0026thinsp;=\u0026thinsp;0.185). However, hypotension (10.2% vs 1.8%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01), and headache (6.5% vs 0.9%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), occurred more frequently in Ranofer group compared to non-Ranofer group. Seventy-eight (72.9%) in the Ranofer group and 79 (70.5%) subjects in the non-Ranofer group managed to sustain Hb\u0026thinsp;\u0026ge;\u0026thinsp;10 g/dL at the end of the study (p\u0026thinsp;=\u0026thinsp;0.69).\u003c/p\u003e\u003ch2\u003eConclusions:\u003c/h2\u003e \u003cp\u003eRanofer provides similar efficacy compared with other iron preparations for ESKD undergoing long-term hemodialysis in Malaysia. Ranofer is well-tolerated for the patients on hemodialysis. Hypotension and headache were observed to be slightly higher in the Ranofer group, however, the severity and the cause-effect relationship could not be ascertained due to the retrospective nature of this study. The adverse events were expected, and these outcomes were expected to be similar to other iron preparations in the real clinical setting. This study was conducted in accordance with the Declaration of Helsinki and approved by the local ethical committees.\u003c/p\u003e","manuscriptTitle":"The effect of iron (III) hydroxide sucrose complex (Ranofer) and other iron preparations on body iron store in long term hemodialysis patients – A retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-10-03 18:21:59","doi":"10.21203/rs.3.rs-2057589/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"94ee24b7-fa78-4156-bc00-7650e9bd57d3","owner":[],"postedDate":"October 3rd, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-11-07T13:59:49+00:00","versionOfRecord":[],"versionCreatedAt":"2022-10-03 18:21:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2057589","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2057589","identity":"rs-2057589","version":["v1"]},"buildId":"FbvkV6FR0MCFSLy54lSbu","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}