The Antibiotic effect of Silver CAPD Catheter on Peritoneal Dialysis-related infections (ASCA-PD) study: a multicenter randomized open-label trial protocol

The Antibiotic effect of Silver CAPD Catheter on Peritoneal Dialysis-related infections (ASCA-PD) study: a multicenter randomized open-label trial protocol | 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 Antibiotic effect of Silver CAPD Catheter on Peritoneal Dialysis-related infections (ASCA-PD) study: a multicenter randomized open-label trial protocol Masahiro Eriguchi, Yasuhiko Ito, Hisako Yoshida, Masaru Matsui, and 27 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6857752/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 17 Dec, 2025 Read the published version in Trials → Version 1 posted 5 You are reading this latest preprint version Abstract Background: Peritoneal dialysis (PD) offers greater flexibility than hemodialysis, especially in patients with limited mobility or demanding schedules; however, PD-related infection is a major complication and a cause of withdrawal from peritoneal dialysis. The Antibiotic effect of Silver continuous ambulatory peritoneal dialysis (CAPD) Catheter on Peritoneal Dialysis-related infections (ASCA-PD) study will evaluate the effectiveness of a novel silver CAPD catheter, incorporating silver-based antimicrobial technology, for preventing these infections and improving PD adherence. Methods/Design: This randomized, open-label, parallel-group, multicenter trial will evaluate the efficacy and safety of a silver CAPD catheter compared with those of a conventional catheter at 14 Japanese facilities. A total of 250 adult patients with newly initiated PD will be enrolled and randomized 1:1 to receive either catheter type. The key exclusion criteria are prior PD, emergency PD initiation, non-abdominal exit-site placement, metal allergy, life expectancy <1 year, severe liver disease, certain dermatologic conditions, and immunosuppression. After providing informed consent, patients will undergo nasal swab screening for methicillin-resistant Staphylococcus aureus . Randomization will be stratified by facility and diabetes status. The primary outcome is the composite endpoint of all exit-site and tunnel infections within 12 months of PD initiation. Secondary outcomes include individual infection events, catheter removal, peritonitis, catheter patency, allergic reactions, technique failure (transition to hemodialysis for ≥30 days or death), and transition to hybrid dialysis. A Poisson regression model will be used to analyze the primary outcome, adjusting for observation time, treatment group, and stratification factors. Time-to-event secondary outcomes will be analyzed by competing risk regression. Subgroup analyses will be carried out to explore the impacts of age, sex, diabetes, insertion method, and body mass index. Discussion: Unlike previous designs, our silver CAPD catheter incorporates AgNPs into silicone, enabling sustained antimicrobial effects both externally and internally, potentially overcoming limitations seen in prior human studies. This study will demonstrate the efficacy of silver CAPD catheters for preventing PD-related infections, especially during the initiation phase of PD, with the aim of providing a new therapeutic option. Trial registration: Japan Registry of Clinical Trials, jRCTs052250003. Registered on April 4, 2025. Silver CAPD catheter PD-related infections Exit-site infection PD-related peritonitis Peritoneal dialysis Prevention Randomized controlled trial Figures Figure 1 Background Kidney replacement therapies, including hemodialysis (HD), peritoneal dialysis (PD), and kidney transplantation, each present unique advantages and disadvantages. HD and PD are both effective treatment options, with HD currently accounting for approximately 80% of all modalities worldwide [1], while PD and transplantation are less-widely used. One key advantage of PD is its inherent flexibility; in contrast to the thrice-weekly in-center visits required by HD, PD often requires only monthly outpatient appointments, greatly increasing its convenience for students and employed individuals, while home-based PD offers substantial benefits for elderly patients with limited mobility. Its relatively low continuation rate, however, presents a major obstacle to the wider adoption of PD. The reported 3-year technique-survival rates for PD patients are approximately 66%, with PD-catheter-related infections constituting a major cause of technique failure [2]. Moreover, recent Japanese data emphasized the elevated risk of early infections within the initial 30 days of PD initiation, with exit-site infections (ESIs)/tunnel infections (TIs) occurring in 8.5% of patients and PD-related peritonitis in 1.7% [3]. Minimizing PD-related infections, particularly during the initiation phase, is thus crucial for enhancing PD therapy adherence. Various strategies have been implemented to reduce the incidence of PD-catheter-related infections, including optimizing catheter designs (e.g., number of cuffs, Tenckhoff catheter versus swan-neck catheter), adjusting the orientation of the catheter exit site (e.g., upward, sideways, or downward), selecting the exit-site location (e.g., upper abdomen, lower abdomen, or anterior chest), and improving exit-site care protocols. Exit-site care measures include disinfection procedures and modifications to bathing practices, such as open bathing or closed bathing with a patch covering the exit site; however, the approaches differ among facilities, and no standardized guidelines for preventing PD-catheter exit-site infections have yet been established [4]. Few randomized controlled trials have addressed the prevention of PD-related infections, although an ongoing randomized trial is currently comparing three exit-site care strategies, including the use of chlorhexidine patches, the application of prophylactic mupirocin ointment, and usual exit-site care with normal saline [5]. The newly available silver continuous ambulatory peritoneal dialysis (CAPD) catheter is an innovative product comprising silver nanoparticles (AgNPs) uniformly integrated into the silicone catheter material and cuff. Antimicrobial testing demonstrated antimicrobial activity values ranging from 2.9–6.4 against both Gram-positive cocci and Gram-negative bacilli (based on regulatory submission data to the Pharmaceuticals and Medical Devices Agency), and an observational study comparing central venous (CV) catheter ports containing AgNPs with standard CV catheter ports reported a reduction in catheter-port infections by approximately half (0.114 vs. 0.214 per person per 1,000 days) [6]. The current Antibiotic effect of Silver CAPD Catheter on Peritoneal Dialysis-related infections (ASCA-PD) study aims to evaluate the effectiveness of silver CAPD catheters for preventing PD-catheter-related infections during the first year after initiating PD. We hypothesize that silver CAPD catheters will be superior to conventional CAPD catheters in terms of PD-catheter-related infections during the PD initiation period. Methods Study Setting The ASCA-PD study is a randomized, open-label, parallel-group, multicenter clinical trial. The study will be conducted at 14 facilities in Japan: Nara Medical University, Aichi Medical University, St. Marianna University, Kokura Memorial Hospital, Kansai Electric Power Hospital, Nagoya University, Kawasaki Medical University, Nippon Medical University, Shinshu University, Kameda Medical Center, National Hospital Organization Kure Medical Center, Saiseikai Yokohamashi Tobu Hospital, Matsuyama Red Cross Hospital, and Tagawa Municipal Hospital. The study will be carried out as “Specified Clinical Research” under the Clinical Trials Act of Japan and has been registered with Japan Registry of Clinical Trials (jRCTs052250003). The study protocol was drafted in accordance with the Standard Protocol Items: Recommendations for Intervention Trials (SPIRIT) statement. All items from the World Health Organization Trial Registration Data Set for this study are available in the jRCTs database at https://jrct.mhlw.go.jp/en-latest-detail/jRCTs052250003. Eligibility Criteria The inclusion and exclusion criteria are provided in Table 1. The study will enroll patients aged ≥18 years who are newly initiating PD. Exclusion criteria include patients reinitiating PD after kidney transplantation or hemodialysis, requiring catheter insertion for emergency PD initiation, scheduled to have the exit site created outside the upper or lower abdomen, and patients with a history of metal allergy. Patients with a life expectancy <1 year at the time of PD initiation (e.g., patients with terminal cancer), and patients with severe liver cirrhosis (Child-Pugh class C), dermatological conditions such as psoriasis vulgaris or atopic dermatitis, gastrostomy or colostomy, and patients receiving immunosuppressive therapy including corticosteroids will also be excluded from the study. Patient Recruitment, Screening, and Run-in All patients scheduled for planned PD induction will be screened according to the inclusion and exclusion criteria and recruited into the study at each participating facility over a period of 18 months. The study flow after obtaining consent is shown in Figure 1. After pre-registration, a nasal swab screening culture will be performed promptly, and any detected cases of methicillin-resistant Staphylococcus aureus will be treated with mupirocin ointment (twice daily for 5 days) before surgery. The final registration will be conducted at the initiation of PD. When catheter insertion is performed for stepwise PD initiation using the Moncrieff and Popovich technique (SMAP) [7], the final registration will occur at the time of exit-site creation for PD initiation. Randomization Patients will be randomized centrally in a 1:1 ratio to receive either a silver CAPD catheter or a conventional catheter. Randomization will be performed by the central study office, an independent facility from the participating sites (Department of Medical Statistics, Osaka Metropolitan University Graduate School of Medicine), using a pre-generated allocation table based on stratified permuted block randomization. To ensure balanced treatment groups, randomization will be stratified by participating facility and the presence of diabetes mellitus (DM), using randomly permuted blocks. Intervention The principal investigator or the sub-investigators will implant either a silver CAPD catheter (Fuji Systems Corporation, Tokyo, Japan) or a conventional catheter, according to the assigned treatment arm. The implantation procedure, insertion site, surgical instruments, location of exit site (lower abdominal/upper abdominal exit site) and catheter fixation methods will follow standard clinical practice and are not specifically restricted by this study; however, the implantation technique should be standardized within each participating facility, and remain consistent regardless of the catheter type (silver-impregnated CAPD catheter or conventional catheter). Timeline and Assessment The assessment schedule and timeline are presented in Table 2 (SPIRIT figure). Data will be collected at six key time points: (1) at registration (before catheter insertion); (2) at the time of catheter insertion; (3) at PD initiation (exit-site creation); (4) at follow-up visits every 3 months post-PD initiation; (5) at the time of ESIs/TIs or peritonitis; and (6) at the final observation. Details of the assessments and procedures at each time point are described below. 1. Registration (before catheter insertion) Each patient’s eligibility for the study will be confirmed prior to catheter insertion, and any relevant randomization factors will be determined. Baseline medical history and background information will be collected, including the primary cause of kidney disease, presence of DM, heart failure, or cardiovascular disease, date of birth and sex. A nasal swab culture will also be obtained at this stage. 2. Time of catheter insertion During catheter insertion, information regarding the surgery will be recorded, including the date of surgery, surgical method (whether SMAP is used), catheter details (type, length, and number of cuffs), and the use of perioperative prophylactic antibiotics. Any adverse events (AEs) or serious AEs (SAEs) occurring in relation to the procedure will also be documented at this time. 3. PD initiation (exit-site creation) A range of clinical assessments will be conducted when the patient initiates PD and undergoes exit-site creation. A physical examination will be carried out to measure the patient’s height, weight, blood pressure (systolic/diastolic), and heart rate. Laboratory tests will be performed to evaluate white blood cell count, hemoglobin, platelet count, serum albumin, serum electrolytes (sodium, potassium, chloride), blood urea nitrogen, serum creatinine, serum calcium, serum phosphorus, glycated hemoglobin, C-reactive protein, transferrin saturation, ferritin, and intact parathyroid hormone. Information on concomitant medications, specifically, oral potassium supplements, antacids, iron supplementation, and erythropoiesis-stimulating agents/hypoxia-inducible factor prolyl hydroxylase inhibitors, will be collected. Surgical details (including the use of perioperative prophylactic antibiotics) and PD-related data (date of PD initiation, modality [CAPD or ambulatory peritoneal dialysis, APD], use of assisted PD, sterile connector systems, icodextrin, and glucose concentration in the dialysate) will also be documented. Exit-site care practices such as taping, disinfection method, gauze protection, and exit-site location (above or below the umbilicus) will be recorded. Any AEs or SAEs will be carefully monitored and reported. Whenever possible, results obtained during the inpatient period for PD initiation will be prioritized; however, if height, weight, or glycated hemoglobin data are available from within 3 months prior to obtaining informed consent, these may be substituted if current data are unavailable. 4. Follow-up visits (every 3 months post-PD initiation) Patients will return for follow-up visits approximately every 3 months after PD initiation, specifically at 3, 6, 9, and 12 months (weeks 13, 26, 39, and 52 post-exit-site creation, respectively, with allowable windows of ±3 weeks). If patients cannot attend on the exact scheduled date because of public holidays, year-end closures, or hospitalization in another department or institution, they will be assessed at a time as close as possible to the designated timeframe. At each follow-up visit, information will be collected regarding the PD regimen (CAPD vs. APD, use of assisted PD, sterile connector systems, icodextrin, and dialysate glucose concentration), along with details of exit-site care (taping, disinfection method, gauze protection) and the exit-site score (Supplemental Table 1) [8]. Any AEs or SAEs will be recorded. In addition, data on antibiotics prescribed for reasons unrelated to catheter infection (e.g., type of antibiotic, duration of administration) will be gathered. 5. Time of ESI/TI or peritonitis The exit-site score will be evaluated whenever an ESI/TI or peritonitis occurs, and detailed information concerning the infection will be obtained. For ESIs/TIs, this includes determining if the infection involves only the exit site, the tunnel, or both, as well as performing Gram staining, culture of the exit site, and catheter culture (in cases where the catheter is removed). The type of antibiotic therapy (including duration and route of administration) and any surgical interventions (unroofing, exit-site revision, or catheter removal) will also be documented. In cases of peritonitis, the dialysate cell count, percentage of neutrophils, potential cause of peritonitis, and dialysate culture results will be recorded. The type and duration of antibiotic treatment and any surgical interventions (such as catheter removal) will also be noted. Any AEs or SAEs will be comprehensively recorded during these events. 6. Final observation PD-related outcomes such as catheter patency, technique failure (defined as transition to hemodialysis for ≥30 days or death), or conversion to a hybrid therapy (concurrent PD and HD) will be examined at the final observation point. In addition, exit-site care methods, exit-site score, and any evidence of colony formation on the catheter exit portion will be assessed. Finally, all AEs and SAEs up to this point will be evaluated and reported. Outcomes The primary and secondary outcomes are summarized in Table 3. The primary outcome is the composite endpoint of all ESIs/TIs occurring within 12 months after PD initiation. The rationale for this approach is to maximize the analytical sensitivity by comparing multiple infection events, allowing for a more comprehensive assessment of treatment effectiveness. The definitions of ESIs and TIs in this study follow the ISPD guidelines [4]. An ESI is defined as the presence of purulent discharge at the catheter exit site, regardless of the presence of erythema on the surrounding skin. In contrast, if purulent discharge is absent, other inflammatory signs at the exit site (e.g. erythema, tenderness, swelling, granuloma or crust formation) are not sufficient for a definitive diagnosis of an ESI. A TI is defined as the presence of clinical signs of inflammation (erythema, swelling, tenderness, or induration) along the catheter tunnel, regardless of the presence of ultrasonographic findings indicating fluid accumulation along the tunnel [4]. This study will evaluate several secondary outcomes. We will assess all ESIs/TIs or PD-related peritonitis occurring within 12 months of PD initiation, with catheter removal unrelated to infection and death treated as competing events. The first occurrence of ESIs/TIs or PD-related peritonitis within 12 months of PD initiation will also be evaluated, with catheter removal unrelated to infection and death considered as competing events. PD-related peritonitis is diagnosed when at least two of the following criteria are met: 1) clinical signs consistent with peritonitis (abdominal pain and/or cloudy effluent); 2) effluent white blood cell count >100/mL or >0.1×10 9 /L (after ≥2 hours dwell) with >50% polymorphonuclear leukocytes; and/or 3) positive effluent culture [9]. We will also measure all ESIs/TIs and all episodes of peritonitis within 30 days of PD initiation, in accordance with the 2023 ISPD guidelines [4]. All-cause catheter removal after insertion is included as an outcome. A composite endpoint of PD-related infections requiring surgical intervention, defined as infections necessitating catheter removal, exit-site relocation, unroofing, or cuff shaving for subcutaneous cuff extrusion, and death within 30 days of catheter insertion due to peritonitis will be assessed. Catheter patency will be evaluated, defined as the absence of surgical or radiological interventions including catheter removal due to complications such as catheter-tip migration, suboptimal placement, tubing kinks, omental wrapping, fibrin or blood clots, preexisting adhesions, obstruction by epiploic appendices or uterine tubes, pericatheter hernia, and intractable drain pain due to excessively deep pelvic catheter tip placement [3]. Following catheter insertion, we will assess allergic reactions, including contact dermatitis, eosinophilia, and eosinophilic peritonitis, as well as refractory and recurrent ESIs/TIs and peritonitis [9, 4]. Exit-site colonization and culture results will be analyzed 12 months after PD initiation or at the time of catheter removal within that 12-month period. Technique failure, defined as transition to hemodialysis for ≥30 days or death (excluding kidney transplantation), will be assessed [10]. Finally, the transition from PD to hybrid therapy (combination of HD and PD) will be evaluated. Data management and monitoring The data used in this study will be transferred from each participating medical institution to the data center via a secure cloud server. For numerical data entry, range restrictions will be implemented for each variable to prevent the input of out-of-range values, and for categorical data, all entries will be made using predefined pull-down lists. Access to the collected data stored at the data center will be permitted only to the study administrative office, monitoring personnel, and statistical analysis personnel, based on specific access privileges controlled through user IDs and passwords for the cloud server. Data checking and monitoring for this study will be conducted on a semiannual basis by the Department of Medical Statistics, Osaka Metropolitan University Graduate School of Medicine, which is independent from all participating sites involved in patient recruitment. Safety Monitoring and Study Auditing Safety monitoring will be conducted in accordance with the protocol. All AEs related to the study device or procedure must be reported promptly to the Nara Medical University Safety Office upon detection. Reports to the Ministry of Health, Labour and Welfare will be submitted within 15 or 30 days of occurrence, depending on the severity. AEs resulting in death, regardless of whether a relationship to the study device is known or suspected, will be reported within 15 days. AEs requiring surgical intervention for the catheter, such as ESIs, TIs, peritonitis, and events such as encapsulating peritoneal sclerosis, omental wrapping, obstruction by epiploic appendices or uterine tubes, pleuroperitoneal communication, pericatheter hernia, catheter occlusion by fibrin or blood clots, self-removal, or damage, will be reported within 30 days. Other SAEs suspected to be related to the study will also be reported within 30 days. Hospitalization solely for daily antibiotic administration was excluded. Non-SAEs, including catheter-related infections not requiring hospitalization, other catheter-related complications not requiring hospitalization, and other non-SAE events suspected to be related to the study, will be reported annually to the Ministry of Health, Labour and Welfare. Data for these events will be collected from the case report forms. Statistical Analyses The full analysis set (FAS) will serve as the primary population for efficacy analyses and will adhere to the intention-to-treat principle. The FAS will include all randomized participants, except those who withdrew consent after registration, were found to be ineligible after registration, who did not undergo catheter insertion, and who had no data relevant to efficacy evaluation following catheter insertion. The data center will assess deviations from the study protocol as data accumulates. Prior to database locking, a case review meeting will be held, including the principal investigator, the lead statistician, representatives from the data center, and members of the monitoring team, to define and identify cases with major deviations from the study protocol. A per-protocol set will be derived from the FAS, including patients with no major deviations from the study protocol. This population will be used for supplementary efficacy analyses. Descriptive statistics regarding patient demographics and baseline characteristics will be calculated for each treatment group. Continuous variables will be summarized using the number of patients, mean, standard deviation, minimum, first quartile (Q1: 25th percentile), median, third quartile (Q3: 75th percentile), and maximum. Categorical variables will be presented as numbers of patients and percentages. The frequencies and percentages of patients with specific comorbidities and prior medication use will also be determined for each treatment group. For the primary endpoint analysis, the number of primary endpoint events recorded during the observation period for each patient will be analyzed using a Poisson regression model, with the observation period (in months) included as an offset term. Independent variables will include the treatment group (silver CAPD catheter vs. conventional catheter) and the randomization stratification factors (DM status and study site). The treatment effect and its 95% confidence interval and significance will be estimated to evaluate differences in event incidence rates between the groups. Predefined subgroup analyses will be conducted based on age (≥75 years vs. <75 years), sex, presence of DM, type of catheter insertion method (SMAP vs. conventional method), and body mass index at the time of consent (≥25 kg/m² vs. <25 kg/m²). Secondary outcomes will be analyzed using appropriate regression models depending on the outcome type (e.g., time-to-event analysis, competing risk models, logistic regression). Details on how missing data will be handled, as well as statistical models and sensitivity analysis, will be specified in the Statistical Analysis Plan, which will be finalized prior to database locking. No formal interim analysis for efficacy evaluation is planned, but a blinded review of enrollment progress and event accumulation will be conducted when 50% of the planned participants have been enrolled. This review will be conducted by the lead statistician without access to treatment assignment, and will not involve any hypothesis testing, to avoid influencing the final analysis. Specifically, this review will consider recruitment status, dropout rate, and the overall number of primary endpoint events observed in both treatment groups combined at 12 months post-enrollment. Powering and Sample Size There are currently no established data on the incidence of infections at 12 months postoperatively in PD patients who have undergone exit-site creation with a silver CAPD catheter. Based on a previous study examining the efficacy of silver-mixed port used in totally implantable venous access ports [6], we set the relative risk for the primary endpoint of the silver CAPD catheters compared with that of conventional catheters at 0.5 (with event incidence rates of 0.4 for conventional catheters and 0.2 for silver CAPD catheters). Assuming a two-sided significance level of 5% and a power of 80%, the required sample size per group is 92 patients, equating to a total sample size of 184 when allocating patients in a 1:1 ratio between the silver CAPD catheter group and the conventional catheter group. Considering the design of this study, however, we anticipate that a certain number of cases will not proceed to final enrollment (exit-site creation) after allocation and will be excluded at the end of the enrollment period. Assuming that this proportion will be approximately 25%, the target sample size was set at 250 patients. Ethics The silver CAPD catheter has been certified by the Pharmaceuticals and Medical Devices Agency in Japan. Regulatory and ethical approval will be obtained from the Certified Review Board at each hospital. The ASCA-PD study will be conducted in accordance with the International Conference on Harmonization Good Clinical Practice guidelines and with the key principles of ethical conduct in research and the Declaration of Helsinki. The sponsor will not be involved with study design, or in data assembly and analysis. Confidentiality Personal information about potential and enrolled participants will be collected, stored, and processed with strict safeguards to protect confidentiality before, during, and after the trial, in accordance with applicable data protection regulations. Each participant will be identified by a unique patient identification number, and a participant identification code list linking these numbers to personal information will be prepared and securely stored within the trial site. This list will not be disclosed outside the trial site. When the results of the study are published, data will be presented in a manner that ensures individual participants cannot be identified. If a participant requests disclosure of retained personal information that can identify them, the principal investigator will, without undue delay, provide the relevant information to the participant. Upon request, the principal investigator will also disclose the study protocol and details of the study. Data access Access to the final trial dataset will be limited to the principal investigators and the study statistician. There are no contractual agreements that limit such access for the investigators. Ancillary and post-trial care This study will be conducted within the scope of standard health insurance coverage, with no off-label medications or uninsured tests used. In the event of a study-related health injury, appropriate treatment will be provided under the public health insurance system, and the Relief System for Adverse Drug Reactions may apply when relevant. The principal investigator will obtain both liability and compensation insurance to cover health injuries causally related to study participation. Dissemination policy The trial results will be presented at scientific meetings and published in peer-reviewed journals, and will also be reported to the jRCTs, typically within one year after the final results become available. Professional medical writers will not be used. The complete study protocol will be provided as a supplementary file. Discussion At the end of the 2021 fiscal year, approximately 340,000 patients were receiving dialysis treatment in Japan, with a prevalence of 2,786 per million population. This figure is significantly higher than in most European countries, where the prevalence is generally <1,000 per million population [11]. Most dialysis patients in Japan receive HD, with only 3.2% of the total dialysis population (approximately 10,000 patients) receiving PD. This proportion is strikingly lower than in regions such as Hong Kong and Thailand, where PD accounts for 23%–72% of dialysis modalities, owing to the adoption of a PD-first policy [12, 13]. Approximately 272,000 patients with end-stage kidney disease undergo PD globally, representing around 11% of the total dialysis population [13]. One of the primary reasons for the limited adoption of PD in Japan is the occurrence of PD-related infections such as ESI, TIs, and PD-associated peritonitis, leading to technique failure [14]. Preventive strategies for exit-site care, including the use of dressings and the application of topical antibiotic ointments, have been investigated to reduce PD-related infections [15-22]. The efficacy of dressings in preventing PD-related infections has not been demonstrated [15, 16] and the routine use of topical antibiotic ointments at catheter exit sites has not been widely adopted in Japan, mainly due to regulatory limitations regarding approved indications [23]. A recent systematic review and meta-analysis did not demonstrate significant effectiveness of mupirocin ointment in preventing ESI.[24], and the 2023 revision of the ISPD guidelines consequently downgraded the recommendation for the application of topical antibiotics at the exit site [4]. There are currently no fully established guidelines for preventing PD-catheter exit-site infections. The antimicrobial effects of AgNPs have long been recognized. They have demonstrated broad-spectrum antimicrobial activity in vitro [25, 26], and studies investigating the effectiveness of AgNP-coated PD catheters in preventing ESIs/TIs and PD-related peritonitis have been conducted in both animal and human subjects [27-30]. Although animal studies demonstrated their ability to prevent infections [27, 28], however, randomized controlled trials in humans failed to confirm the protective effects of AgNP-coated catheters or silver ring devices placed at the exit site [29, 30]. One possible reason for the lack of efficacy in humans was that the AgNP coating was only applied to the exterior of the catheter, and the duration of the antimicrobial effect of the AgNP coating was limited. In contrast, the silver PD catheter used in the current study incorporates AgNPs into the silicone material, allowing for a sustained antimicrobial effect on both the external and internal surfaces of the catheter. This study will examine the efficacy of silver CAPD catheters with incorporated AgNPs for preventing PD-related infections, particularly during the initiation phase of PD. Trial status This manuscript was prepared based on Trial Protocol Version 1.1, dated February 14, 2025. Patient enrollment commenced on May 1, 2025, with a target of enrolling 250 patients by December 31, 2026. The first patient was enrolled on May 15, 2025. List of abbreviations APD: automated peritoneal dialysis; CAPD: continuous ambulatory peritoneal dialysis; ESI: exit-site infection; HD: hemodialysis; ISPD: International Society for Peritoneal Dialysis; PD: peritoneal dialysis; SMAP: stepwise initiation of PD using Moncrief and Popovich; TI: tunnel infection Declarations Acknowledgments We sincerely appreciate the support provided for protocol development, research design planning, ethical and legal requirements review, and Certified Review Board application assistance by all members of the Institute for Clinical and Translational Science (iCATs) at Nara Medical University Hospital, including Prof. Masato Kasahara, Dr. Hiroyuki Kurakami, Dr. Kyouko Sakai, Dr. Kiyoshi Asada, Ryuzo Takashima, Yuriko Ito, Miu Kojima, and Mineko Yamaguchi. We also thank Susan Furness, PhD, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript. Disclosure Statement The authors declare no conflicts of interest related to this study. Fuji Systems Corporation provided technical support but had no role in the study design, data collection, analysis, interpretation, or manuscript preparation. Funding Sources This study was supported by the Clinical Research Grant Program of Nara Medical University (Grant number: JHR2400003), the Public Research Grant from the Japanese Association of Dialysis Physicians (JADP Grant 2024-8), and operational funding provided by Fuji Systems Corporation to support the conduct of the clinical study. Author Contributions M.E. wrote the first draft of the paper and was involved in the study design. Y.I. had final responsibility for the decision to submit for publication. Y.I., H.Y., and M.Matsui contributed to the study concept and design and conducted the process evaluation. T.K., A.N., G.T., S.Ya., T.Sa., M.N., K.Ha., S.Ku., N.T., S.O., M.Mi., H.K., S.Ki., S.Ku., Y.S., K.Ha., M.M., T.Su., S.T., K.N., K.K., H.O., T.Ka., H.M., and T.Y. support trial management and coordination. KT is the trial Chief Investigator. All authors provided critical review of the manuscript for important intellectual content. All authors read and approved the final manuscript. Availability of data and materials Data sharing is not applicable to this study because no datasets were generated or analyzed; however, the study data will be made available upon reasonable request after completion of the trial. Ethics approval and consent to participate The study protocol and informed consent documents have been approved by the Certified Review Board, with Nara Medical University as the principal research institution (approval number: nara0065). Any important protocol modifications (e.g., changes to eligibility criteria, outcomes, or analyses) will be promptly communicated to all relevant parties, including the principal investigator, the research ethics committee, the Certified Review Board, the jRCTs, and the Ministry of Health, Labour and Welfare of Japan. Based on this approval, the study will be initiated at each participating site after obtaining implementation permission from the respective institutions. Written informed consent will be obtained from all study participants by the site principal investigator or a sub-investigator, according to the Declaration of Helsinki. Consent for publication Consent for publication is not applicable. Competing interests The authors declare that they have no competing interests. All researchers conducted this study as part of their academic research activities. References United States Renal Data System. 2023 Annual Data Report. End Stage Renal Disease: Chapter 11 International Comparisons. 2023. https://usrds-adr.niddk.nih.gov/2023/end-stage-renal-disease/11-international-comparisons. Accessed May 30, 2024 2024. Kolesnyk I, Dekker FW, Boeschoten EW, Krediet RT. Time-dependent reasons for peritoneal dialysis technique failure and mortality. Perit Dial Int. 2010;30(2):170-7. doi:10.3747/pdi.2008.00277. Sakurada T, Kojima S, Yamada S, Koitabashi K, Taki Y, Matsui K et al. A multi-institutional, observational study of outcomes after catheter placement for peritoneal dialysis in Japan. Perit Dial Int. 2023;43(6):457-66. doi:10.1177/08968608231193240. Chow KM, Li PK, Cho Y, Abu-Alfa A, Bavanandan S, Brown EA et al. ISPD Catheter-related Infection Recommendations: 2023 Update. Perit Dial Int. 2023;43(3):201-19. doi:10.1177/08968608231172740. Nochaiwong S, Ruengorn C, Noppakun K, Panyathong S, Dandecha P, Sood MM et al. Comparative Effectiveness of Local Application of Chlorhexidine Gluconate, Mupirocin Ointment, and Normal Saline for the Prevention of Peritoneal Dialysis-related Infections (COSMO-PD Trial): a multicenter randomized, double-blind, controlled protocol. Trials. 2019;20(1):754. doi:10.1186/s13063-019-3953-8. Suzuki T, Michimoto K, Hasumi J, Kisaki S, Hasegawa Y, Fujimori A et al. Silver-Mixed Port Reduces Venous Access Port Related Infection Rate Compared to Non-Silver-mixed Port: A Single-center Retrospective Analysis. Cardiovasc Intervent Radiol. 2023;46(12):1696-702. doi:10.1007/s00270-023-03583-y. Moncrief JW, Popovich RP, Dasgupta M, Costerton JW, Simmons E, Moncrief B. Reduction in peritonitis incidence in continuous ambulatory peritoneal dialysis with a new catheter and implantation technique. Perit Dial Int. 1993;13 Suppl 2:S329-31. Eriguchi M, Tsuruya K, Yoshida H, Yamada S, Tanaka S, Suehiro T et al. Validation of the exit-site scoring system recommended by the 2005 guidelines of the International Society for Peritoneal Dialysis. Perit Dial Int. 2011;31(6):698-700. doi:10.3747/pdi.2010.00287. Li PK, Chow KM, Cho Y, Fan S, Figueiredo AE, Harris T et al. ISPD peritonitis guideline recommendations: 2022 update on prevention and treatment. Perit Dial Int. 2022;42(2):110-53. doi:10.1177/08968608221080586. Htay H, Cho Y, Pascoe EM, Darssan D, Nadeau-Fredette AC, Hawley C et al. Multicenter Registry Analysis of Center Characteristics Associated with Technique Failure in Patients on Incident Peritoneal Dialysis. Clin J Am Soc Nephrol. 2017;12(7):1090-9. doi:10.2215/CJN.12321216. Hanafusa N, Abe M, Joki N, Hoshino J, Wada A, Kikuchi K et al. Annual dialysis data report 2021, Japanese Society for Dialysis Therapy (JSDT) renal data registry. Renal Replacement Therapy. 2024;10(1):78. Chuengsaman P, Kasemsup V. PD First Policy: Thailand's Response to the Challenge of Meeting the Needs of Patients With End-Stage Renal Disease. Semin Nephrol. 2017;37(3):287-95. doi:10.1016/j.semnephrol.2017.02.008. Li PK, Chow KM, Van de Luijtgaarden MW, Johnson DW, Jager KJ, Mehrotra R et al. Changes in the worldwide epidemiology of peritoneal dialysis. Nat Rev Nephrol. 2017;13(2):90-103. doi:10.1038/nrneph.2016.181. Davies SJ, Phillips L, Griffiths AM, Russell LH, Naish PF, Russell GI. What really happens to people on long-term peritoneal dialysis? Kidney Int. 1998;54(6):2207-17. doi:10.1046/j.1523-1755.1998.00180.x. Mushahar L, Mei LW, Yusuf WS, Sivathasan S, Kamaruddin N, Idzham NJ. Exit-Site Dressing and Infection in Peritoneal Dialysis: A Randomized Controlled Pilot Trial. Perit Dial Int. 2016;36(2):135-9. doi:10.3747/pdi.2014.00195. Taheri S, Ahmadnia M, Mortazavi M, Karimi S, Reihani H, Seirafian S. Comparing the Effect of Dressing Versus No-dressing on Exit Site Infection and Peritonitis in Chronic Ambulatory Peritoneal Dialysis Patients. Adv Biomed Res. 2017;6:5. doi:10.4103/2277-9175.199263. Bernardini J, Bender F, Florio T, Sloand J, Palmmontalbano L, Fried L et al. Randomized, double-blind trial of antibiotic exit site cream for prevention of exit site infection in peritoneal dialysis patients. J Am Soc Nephrol. 2005;16(2):539-45. doi:10.1681/ASN.2004090773. McQuillan RF, Chiu E, Nessim S, Lok CE, Roscoe JM, Tam P et al. A randomized controlled trial comparing mupirocin and polysporin triple ointments in peritoneal dialysis patients: the MP3 Study. Clin J Am Soc Nephrol. 2012;7(2):297-303. doi:10.2215/CJN.07970811. Findlay A, Serrano C, Punzalan S, Fan SL. Increased peritoneal dialysis exit site infections using topical antiseptic polyhexamethylene biguanide compared to mupirocin: results of a safety interim analysis of an open-label prospective randomized study. Antimicrob Agents Chemother. 2013;57(5):2026-8. doi:10.1128/AAC.02079-12. Nunez-Moral M, Sanchez-Alvarez E, Gonzalez-Diaz I, Pelaez-Requejo B, Fernandez-Vina A, Quintana-Fernandez A et al. Exit-site infection of peritoneal catheter is reduced by the use of polyhexanide. results of a prospective randomized trial. Perit Dial Int. 2014;34(3):271-7. doi:10.3747/pdi.2012.00109. Tam BM, Chow SK. A preliminary report on the effectiveness of nanotechnology anti-microbial spray dressing in preventing Tenckhoff catheter exit-site infection. Perit Dial Int. 2014;34(6):670-3. doi:10.3747/pdi.2013.00199. Zhang L, Badve SV, Pascoe EM, Beller E, Cass A, Clark C et al. The Effect of Exit-Site Antibacterial Honey Versus Nasal Mupirocin Prophylaxis on the Microbiology and Outcomes of Peritoneal Dialysis-Associated Peritonitis and Exit-Site Infections: A Sub-Study of the Honeypot Trial. Perit Dial Int. 2015;35(7):712-21. doi:10.3747/pdi.2014.00206. Ito Y, Ryuzaki M, Sugiyama H, Tomo T, Yamashita AC, Ishikawa Y et al. Peritoneal Dialysis Guidelines 2019 Part 1 (Position paper of the Japanese Society for Dialysis Therapy). Renal Replacement Therapy. 2021;7(1). doi:10.1186/s41100-021-00348-6. Obata Y, Murashima M, Toda N, Yamamoto S, Tsujimoto Y, Tsujimoto Y et al. Topical application of mupirocin to exit sites in patients on peritoneal dialysis: a systematic review and meta-analysis of randomized controlled trials. Renal Replacement Therapy. 2020;6(1). doi:10.1186/s41100-020-00261-4. Lara HH, Garza-Trevino EN, Ixtepan-Turrent L, Singh DK. Silver nanoparticles are broad-spectrum bactericidal and virucidal compounds. J Nanobiotechnology. 2011;9:30. doi:10.1186/1477-3155-9-30. Patel V, Berthold D, Puranik P, Gantar M. Screening of cyanobacteria and microalgae for their ability to synthesize silver nanoparticles with antibacterial activity. Biotechnol Rep (Amst). 2015;5:112-9. doi:10.1016/j.btre.2014.12.001. Dasgupta M. Autochthonous bacterial spread from catheter exit site is reduced by silver catheter. Perit Dial Int. 1995;15:S49. Fung LC, Khoury AE, Vas SI, Smith C, Oreopoulos DG, Mittelman MW. Biocompatibility of silver-coated peritoneal dialysis catheter in a porcine model. Perit Dial Int. 1996;16(4):398-405. Pommer W, Brauner M, Westphale HJ, Brunkhorst R, Kramer R, Bundschu D et al. Effect of a silver device in preventing catheter-related infections in peritoneal dialysis patients: silver ring prophylaxis at the catheter exit study. Am J Kidney Dis. 1998;32(5):752-60. doi:10.1016/s0272-6386(98)70130-1. Crabtree JH, Burchette RJ, Siddiqi RA, Huen IT, Hadnott LL, Fishman A. The efficacy of silver-ion implanted catheters in reducing peritoneal dialysis-related infections. Perit Dial Int. 2003;23(4):368-74. Tables Table 1 Inclusion and exclusion criteria Inclusion criteria Exclusion criteria • Participants aged 18 years or over at the date of screening • Incident patients initiating PD according to a pre-planned schedule • Patients reinitiating PD after kidney transplantation or hemodialysis • Patients scheduled to have the exit site created outside the upper or lower abdomen • Patients with a history of metal allergy (including silver) • Patients with an expected life expectancy of less than one year at the time of PD initiation (e.g., patients with terminal cancer) • Patients with severe liver cirrhosis (Child-Pugh class C) • Patients with dermatological conditions such as psoriasis vulgaris or atopic dermatitis • Patients with a gastrostomy or colostomy • Patients receiving immunosuppressive therapy (including oral and/or intravenous corticosteroids) PD: peritoneal dialysis Table 2 is available in the Supplementary Files section. Table 3 Primary and secondary outcomes Primary outcome Composite endpoint of all exit-site and tunnel infections occurring within 12 months after PD initiation Secondary outcomes 1. All exit-site and tunnel infections occurring within 12 months after PD initiation, with catheter removal unrelated to infection and death treated as competing events 2. First occurrence of exit-site or tunnel infection within 12 months after PD initiation 3. First occurrence of exit-site or tunnel infection within 12 months after PD initiation, with catheter removal unrelated to infection and death treated as competing events 4. All exit-site and tunnel infections occurring within 30 days after PD initiation 5. All episodes of peritonitis occurring after catheter insertion 6. Catheter removal of any cause after insertion 7. Composite of PD-related infections requiring surgical intervention* 1 , and death within 30 days due to peritonitis after catheter insertion 8. Catheter patency* 2 9. Allergic reactions such as contact dermatitis, eosinophilia, and eosinophilic peritonitis after catheter insertion 10. Refractory and recurrent exit-site/tunnel infections and peritonitis 11. Presence of colonization at the exit site and culture results at the end of the observation period* 3 12. Technique failure* 4 13. Transition from peritoneal dialysis to hybrid therapy (combination of HD and PD) * 1 PD-related infections requiring surgical intervention are defined as catheter removal, relocating exit site, unroofing, and cuff shaving for subcutaneous cuff extrusion * 2 Catheter patency is defined as the absence of catheter tip migration or suboptimal placement, tubing kinks, omental wrapping, fibrin/blood clots, preexisting adhesions, obstruction by epiploic appendices or uterine tubes, pericatheter hernia, and intractable drain pain due to excessively deep pelvic catheter tip placement. * 3 Twelve months after PD initiation or at the time of catheter removal within 12 months * 4 Technique failure was defined as transition to hemodialysis for ≥30 days or death, excluding kidney transplantation. PD: peritoneal dialysis, HD: hemodialysis Supplementary Files Table2Participanttimeline.docx 20250516SuppleASCAPDstudyprotcolpaper.docx 20250815SPIRITchecklist.docx Cite Share Download PDF Status: Published Journal Publication published 17 Dec, 2025 Read the published version in Trials → Version 1 posted Reviewers agreed at journal 28 Sep, 2025 Reviewers invited by journal 19 Aug, 2025 Editor assigned by journal 17 Aug, 2025 First submitted to journal 15 Aug, 2025 Editorial decision: Major revision 23 Jul, 2025 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. We do this by developing innovative software and high quality services for the global research community. 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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-6857752","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":502373322,"identity":"c486b9b6-f0e6-40f4-b055-fe1b5d91345e","order_by":0,"name":"Masahiro 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protocol","fulltext":[{"header":"Background","content":"\u003cp\u003eKidney replacement therapies, including hemodialysis (HD), peritoneal dialysis (PD), and kidney transplantation, each present unique advantages and disadvantages. HD and PD are both effective treatment options, with HD currently accounting for approximately 80% of all modalities worldwide [1], while PD and transplantation are less-widely used. One key advantage of PD is its inherent flexibility; in contrast to the thrice-weekly in-center visits required by HD, PD often requires only monthly outpatient appointments, greatly increasing its convenience for students and employed individuals, while home-based PD offers substantial benefits for elderly patients with limited mobility. Its relatively low continuation rate, however, presents a major obstacle to the wider adoption of PD. The reported 3-year technique-survival rates for PD patients are approximately 66%, with PD-catheter-related infections constituting a major cause of technique failure [2]. Moreover, recent Japanese data emphasized the elevated risk of early infections within the initial 30 days of PD initiation, with exit-site infections (ESIs)/tunnel infections (TIs) occurring in 8.5% of patients and PD-related peritonitis in 1.7% [3]. Minimizing PD-related infections, particularly during the initiation phase, is thus crucial for enhancing PD therapy adherence.\u003c/p\u003e\n\u003cp\u003eVarious strategies have been implemented to reduce the incidence of PD-catheter-related infections, including optimizing catheter designs (e.g., number of cuffs, Tenckhoff catheter versus swan-neck catheter), adjusting the orientation of the catheter exit site (e.g., upward, sideways, or downward), selecting the exit-site location (e.g., upper abdomen, lower abdomen, or anterior chest), and improving exit-site care protocols. Exit-site care measures include disinfection procedures and modifications to bathing practices, such as open bathing or closed bathing with a patch covering the exit site; however, the approaches differ among facilities, and no standardized guidelines for preventing PD-catheter exit-site infections have yet been established [4]. Few randomized controlled trials have addressed the prevention of PD-related infections, although an ongoing randomized trial is currently comparing three exit-site care strategies, including the use of chlorhexidine patches, the application of prophylactic mupirocin ointment, and usual exit-site care with normal saline [5].\u003c/p\u003e\n\u003cp\u003eThe newly available silver continuous ambulatory peritoneal dialysis (CAPD) catheter is an innovative product comprising silver nanoparticles (AgNPs) uniformly integrated into the silicone catheter material and cuff. Antimicrobial testing demonstrated antimicrobial activity values ranging from 2.9\u0026ndash;6.4 against both Gram-positive cocci and Gram-negative bacilli (based on regulatory submission data to the Pharmaceuticals and Medical Devices Agency), and an observational study comparing central venous (CV) catheter ports containing AgNPs with standard CV catheter ports reported a reduction in catheter-port infections by approximately half (0.114 vs. 0.214 per person per 1,000 days) [6]. The current Antibiotic effect of Silver CAPD Catheter on Peritoneal Dialysis-related infections (ASCA-PD) study aims to evaluate the effectiveness of silver CAPD catheters for preventing PD-catheter-related infections during the first year after initiating PD. We hypothesize that silver CAPD catheters will be superior to conventional CAPD catheters in terms of PD-catheter-related infections during the PD initiation period.\u003c/p\u003e"},{"header":"Methods","content":"\u003ch2\u003eStudy Setting\u003c/h2\u003e\n\u003cp\u003eThe ASCA-PD study is a randomized, open-label, parallel-group, multicenter clinical trial. The study will be conducted at 14 facilities in Japan: Nara Medical University, Aichi Medical University, St. Marianna University, Kokura Memorial Hospital, Kansai Electric Power Hospital, Nagoya University, Kawasaki Medical University, Nippon Medical University, Shinshu University, Kameda Medical Center, National Hospital Organization Kure Medical Center, Saiseikai Yokohamashi Tobu Hospital, Matsuyama Red Cross Hospital, and Tagawa Municipal Hospital. The study will be carried out as \u0026ldquo;Specified Clinical Research\u0026rdquo; under the Clinical Trials Act of Japan and has been registered with Japan Registry of Clinical Trials (jRCTs052250003). The study protocol was drafted in accordance with the Standard Protocol Items: Recommendations for Intervention Trials (SPIRIT) statement. All items from the World Health Organization Trial Registration Data Set for this study are available in the jRCTs database at https://jrct.mhlw.go.jp/en-latest-detail/jRCTs052250003.\u003c/p\u003e\n\u003ch2\u003eEligibility Criteria\u003c/h2\u003e\n\u003cp\u003eThe inclusion and exclusion criteria are provided in Table 1. The study will enroll patients aged \u0026ge;18 years who are newly initiating PD. Exclusion criteria include patients reinitiating PD after kidney transplantation or hemodialysis, requiring catheter insertion for emergency PD initiation, scheduled to have the exit site created outside the upper or lower abdomen, and patients with a history of metal allergy. Patients with a life expectancy \u0026lt;1 year at the time of PD initiation (e.g., patients with terminal cancer), and patients with severe liver cirrhosis (Child-Pugh class C), dermatological conditions such as psoriasis vulgaris or atopic dermatitis, gastrostomy or colostomy, and patients receiving immunosuppressive therapy including corticosteroids will also be excluded from the study.\u003c/p\u003e\n\u003ch2\u003ePatient Recruitment, Screening, and Run-in\u003c/h2\u003e\n\u003cp\u003eAll patients scheduled for planned PD induction will be screened according to the inclusion and exclusion criteria and recruited into the study at each participating facility over a period of 18 months. The study flow after obtaining consent is shown in Figure 1. After pre-registration, a nasal swab screening culture will be performed promptly, and any detected cases of methicillin-resistant \u003cem\u003eStaphylococcus aureus\u003c/em\u003e will be treated with mupirocin ointment (twice daily for 5 days) before surgery. The final registration will be conducted at the initiation of PD. When catheter insertion is performed for stepwise PD initiation using the Moncrieff and Popovich technique (SMAP) [7], the final registration will occur at the time of exit-site creation for PD initiation.\u003c/p\u003e\n\u003ch2\u003eRandomization \u003c/h2\u003e\n\u003cp\u003ePatients will be randomized centrally in a 1:1 ratio to receive either a silver CAPD catheter or a conventional catheter. Randomization will be performed by the central study office, an independent facility from the participating sites (Department of Medical Statistics, Osaka Metropolitan University Graduate School of Medicine), using a pre-generated allocation table based on stratified permuted block randomization. To ensure balanced treatment groups, randomization will be stratified by participating facility and the presence of diabetes mellitus (DM), using randomly permuted blocks.\u003c/p\u003e\n\u003ch2\u003eIntervention\u003c/h2\u003e\n\u003cp\u003eThe principal investigator or the sub-investigators will implant either a silver CAPD catheter (Fuji Systems Corporation, Tokyo, Japan) or a conventional catheter, according to the assigned treatment arm. The implantation procedure, insertion site, surgical instruments, location of exit site (lower abdominal/upper abdominal exit site) and catheter fixation methods will follow standard clinical practice and are not specifically restricted by this study; however, the implantation technique should be standardized within each participating facility, and remain consistent regardless of the catheter type (silver-impregnated CAPD catheter or conventional catheter).\u003c/p\u003e\n\u003ch2\u003eTimeline and Assessment\u003c/h2\u003e\n\u003cp\u003eThe assessment schedule and timeline are presented in Table 2 (SPIRIT figure). Data will be collected at six key time points: (1) at registration (before catheter insertion); (2) at the time of catheter insertion; (3) at PD initiation (exit-site creation); (4) at follow-up visits every 3 months post-PD initiation; (5) at the time of ESIs/TIs or peritonitis; and (6) at the final observation. Details of the assessments and procedures at each time point are described below.\u003c/p\u003e\n\u003cp\u003e1. Registration (before catheter insertion)\u003c/p\u003e\n\u003cp\u003eEach patient\u0026rsquo;s eligibility for the study will be confirmed prior to catheter insertion, and any relevant randomization factors will be determined. Baseline medical history and background information will be collected, including the primary cause of kidney disease, presence of DM, heart failure, or cardiovascular disease, date of birth and sex. A nasal swab culture will also be obtained at this stage.\u003c/p\u003e\n\u003cp\u003e2. Time of catheter insertion\u003c/p\u003e\n\u003cp\u003eDuring catheter insertion, information regarding the surgery will be recorded, including the date of surgery, surgical method (whether SMAP is used), catheter details (type, length, and number of cuffs), and the use of perioperative prophylactic antibiotics. Any adverse events (AEs) or serious AEs (SAEs) occurring in relation to the procedure will also be documented at this time.\u003c/p\u003e\n\u003cp\u003e3. PD initiation (exit-site creation)\u003c/p\u003e\n\u003cp\u003eA range of clinical assessments will be conducted when the patient initiates PD and undergoes exit-site creation. A physical examination will be carried out to measure the patient\u0026rsquo;s height, weight, blood pressure (systolic/diastolic), and heart rate. Laboratory tests will be performed to evaluate white blood cell count, hemoglobin, platelet count, serum albumin, serum electrolytes (sodium, potassium, chloride), blood urea nitrogen, serum creatinine, serum calcium, serum phosphorus, glycated hemoglobin, C-reactive protein, transferrin saturation, ferritin, and intact parathyroid hormone. Information on concomitant medications, specifically, oral potassium supplements, antacids, iron supplementation, and erythropoiesis-stimulating agents/hypoxia-inducible factor prolyl hydroxylase inhibitors, will be collected. Surgical details (including the use of perioperative prophylactic antibiotics) and PD-related data (date of PD initiation, modality [CAPD or ambulatory peritoneal dialysis, APD], use of assisted PD, sterile connector systems, icodextrin, and glucose concentration in the dialysate) will also be documented. Exit-site care practices such as taping, disinfection method, gauze protection, and exit-site location (above or below the umbilicus) will be recorded. Any AEs or SAEs will be carefully monitored and reported. Whenever possible, results obtained during the inpatient period for PD initiation will be prioritized; however, if height, weight, or glycated hemoglobin data are available from within 3 months prior to obtaining informed consent, these may be substituted if current data are unavailable.\u003c/p\u003e\n\u003cp\u003e4. Follow-up visits (every 3 months post-PD initiation)\u003c/p\u003e\n\u003cp\u003ePatients will return for follow-up visits approximately every 3 months after PD initiation, specifically at 3, 6, 9, and 12 months (weeks 13, 26, 39, and 52 post-exit-site creation, respectively, with allowable windows of \u0026plusmn;3 weeks). If patients cannot attend on the exact scheduled date because of public holidays, year-end closures, or hospitalization in another department or institution, they will be assessed at a time as close as possible to the designated timeframe. At each follow-up visit, information will be collected regarding the PD regimen (CAPD vs. APD, use of assisted PD, sterile connector systems, icodextrin, and dialysate glucose concentration), along with details of exit-site care (taping, disinfection method, gauze protection) and the exit-site score (Supplemental Table 1) [8]. Any AEs or SAEs will be recorded. In addition, data on antibiotics prescribed for reasons unrelated to catheter infection (e.g., type of antibiotic, duration of administration) will be gathered.\u003c/p\u003e\n\u003cp\u003e5. Time of ESI/TI or peritonitis\u003c/p\u003e\n\u003cp\u003eThe exit-site score will be evaluated whenever an ESI/TI or peritonitis occurs, and detailed information concerning the infection will be obtained. For ESIs/TIs, this includes determining if the infection involves only the exit site, the tunnel, or both, as well as performing Gram staining, culture of the exit site, and catheter culture (in cases where the catheter is removed). The type of antibiotic therapy (including duration and route of administration) and any surgical interventions (unroofing, exit-site revision, or catheter removal) will also be documented. In cases of peritonitis, the dialysate cell count, percentage of neutrophils, potential cause of peritonitis, and dialysate culture results will be recorded. The type and duration of antibiotic treatment and any surgical interventions (such as catheter removal) will also be noted. Any AEs or SAEs will be comprehensively recorded during these events.\u003c/p\u003e\n\u003cp\u003e6. Final observation\u003c/p\u003e\n\u003cp\u003ePD-related outcomes such as catheter patency, technique failure (defined as transition to hemodialysis for \u0026ge;30 days or death), or conversion to a hybrid therapy (concurrent PD and HD) will be examined at the final observation point. In addition, exit-site care methods, exit-site score, and any evidence of colony formation on the catheter exit portion will be assessed. Finally, all AEs and SAEs up to this point will be evaluated and reported.\u003c/p\u003e\n\u003ch2\u003eOutcomes\u003c/h2\u003e\n\u003cp\u003eThe primary and secondary outcomes are summarized in Table 3. The primary outcome is the composite endpoint of all ESIs/TIs occurring within 12 months after PD initiation. The rationale for this approach is to maximize the analytical sensitivity by comparing multiple infection events, allowing for a more comprehensive assessment of treatment effectiveness. The definitions of ESIs and TIs in this study follow the ISPD guidelines [4]. An ESI is defined as the presence of purulent discharge at the catheter exit site, regardless of the presence of erythema on the surrounding skin. In contrast, if purulent discharge is absent, other inflammatory signs at the exit site (e.g. erythema, tenderness, swelling, granuloma or crust formation) are not sufficient for a definitive diagnosis of an ESI. A TI is defined as the presence of clinical signs of inflammation (erythema, swelling, tenderness, or induration) along the catheter tunnel, regardless of the presence of ultrasonographic findings indicating fluid accumulation along the tunnel [4].\u003c/p\u003e\n\u003cp\u003eThis study will evaluate several secondary outcomes. We will assess all ESIs/TIs or PD-related peritonitis occurring within 12 months of PD initiation, with catheter removal unrelated to infection and death treated as competing events. The first occurrence of ESIs/TIs or PD-related peritonitis within 12 months of PD initiation will also be evaluated, with catheter removal unrelated to infection and death considered as competing events. PD-related peritonitis is diagnosed when at least two of the following criteria are met: 1) clinical signs consistent with peritonitis (abdominal pain and/or cloudy effluent); 2) effluent white blood cell count \u0026gt;100/mL or \u0026gt;0.1\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L (after \u0026ge;2 hours dwell) with \u0026gt;50% polymorphonuclear leukocytes; and/or 3) positive effluent culture [9]. We will also measure all ESIs/TIs and all episodes of peritonitis within 30 days of PD initiation, in accordance with the 2023 ISPD guidelines [4]. \u003c/p\u003e\n\u003cp\u003eAll-cause catheter removal after insertion is included as an outcome. A composite endpoint of PD-related infections requiring surgical intervention, defined as infections necessitating catheter removal, exit-site relocation, unroofing, or cuff shaving for subcutaneous cuff extrusion, and death within 30 days of catheter insertion due to peritonitis will be assessed.\u003c/p\u003e\n\u003cp\u003eCatheter patency will be evaluated, defined as the absence of surgical or radiological interventions including catheter removal due to complications such as catheter-tip migration, suboptimal placement, tubing kinks, omental wrapping, fibrin or blood clots, preexisting adhesions, obstruction by epiploic appendices or uterine tubes, pericatheter hernia, and intractable drain pain due to excessively deep pelvic catheter tip placement [3].\u003c/p\u003e\n\u003cp\u003eFollowing catheter insertion, we will assess allergic reactions, including contact dermatitis, eosinophilia, and eosinophilic peritonitis, as well as refractory and recurrent ESIs/TIs and peritonitis [9, 4]. Exit-site colonization and culture results will be analyzed 12 months after PD initiation or at the time of catheter removal within that 12-month period.\u003c/p\u003e\n\u003cp\u003eTechnique failure, defined as transition to hemodialysis for \u0026ge;30 days or death (excluding kidney transplantation), will be assessed [10]. Finally, the transition from PD to hybrid therapy (combination of HD and PD) will be evaluated.\u003c/p\u003e\n\u003ch2\u003eData management and monitoring\u003c/h2\u003e\n\u003cp\u003eThe data used in this study will be transferred from each participating medical institution to the data center via a secure cloud server. For numerical data entry, range restrictions will be implemented for each variable to prevent the input of out-of-range values, and for categorical data, all entries will be made using predefined pull-down lists. Access to the collected data stored at the data center will be permitted only to the study administrative office, monitoring personnel, and statistical analysis personnel, based on specific access privileges controlled through user IDs and passwords for the cloud server. Data checking and monitoring for this study will be conducted on a semiannual basis by the Department of Medical Statistics, Osaka Metropolitan University Graduate School of Medicine, which is independent from all participating sites involved in patient recruitment.\u003c/p\u003e\n\u003ch2\u003eSafety Monitoring and Study Auditing\u003c/h2\u003e\n\u003cp\u003eSafety monitoring will be conducted in accordance with the protocol. All AEs related to the study device or procedure must be reported promptly to the Nara Medical University Safety Office upon detection. Reports to the Ministry of Health, Labour and Welfare will be submitted within 15 or 30 days of occurrence, depending on the severity. AEs resulting in death, regardless of whether a relationship to the study device is known or suspected, will be reported within 15 days. AEs requiring surgical intervention for the catheter, such as ESIs, TIs, peritonitis, and events such as encapsulating peritoneal sclerosis, omental wrapping, obstruction by epiploic appendices or uterine tubes, pleuroperitoneal communication, pericatheter hernia, catheter occlusion by fibrin or blood clots, self-removal, or damage, will be reported within 30 days. Other SAEs suspected to be related to the study will also be reported within 30 days. Hospitalization solely for daily antibiotic administration was excluded. Non-SAEs, including catheter-related infections not requiring hospitalization, other catheter-related complications not requiring hospitalization, and other non-SAE events suspected to be related to the study, will be reported annually to the Ministry of Health, Labour and Welfare. Data for these events will be collected from the case report forms. \u003c/p\u003e\n\u003ch2\u003eStatistical Analyses\u003c/h2\u003e\n\u003cp\u003eThe full analysis set (FAS) will serve as the primary population for efficacy analyses and will adhere to the intention-to-treat principle. The FAS will include all randomized participants, except those who withdrew consent after registration, were found to be ineligible after registration, who did not undergo catheter insertion, and who had no data relevant to efficacy evaluation following catheter insertion. The data center will assess deviations from the study protocol as data accumulates. Prior to database locking, a case review meeting will be held, including the principal investigator, the lead statistician, representatives from the data center, and members of the monitoring team, to define and identify cases with major deviations from the study protocol. A per-protocol set will be derived from the FAS, including patients with no major deviations from the study protocol. This population will be used for supplementary efficacy analyses. Descriptive statistics regarding patient demographics and baseline characteristics will be calculated for each treatment group. Continuous variables will be summarized using the number of patients, mean, standard deviation, minimum, first quartile (Q1: 25th percentile), median, third quartile (Q3: 75th percentile), and maximum. Categorical variables will be presented as numbers of patients and percentages. The frequencies and percentages of patients with specific comorbidities and prior medication use will also be determined for each treatment group.\u003c/p\u003e\n\u003cp\u003eFor the primary endpoint analysis, the number of primary endpoint events recorded during the observation period for each patient will be analyzed using a Poisson regression model, with the observation period (in months) included as an offset term. Independent variables will include the treatment group (silver CAPD catheter vs. conventional catheter) and the randomization stratification factors (DM status and study site). The treatment effect and its 95% confidence interval and significance will be estimated to evaluate differences in event incidence rates between the groups. Predefined subgroup analyses will be conducted based on age (\u0026ge;75 years vs. \u0026lt;75 years), sex, presence of DM, type of catheter insertion method (SMAP vs. conventional method), and body mass index at the time of consent (\u0026ge;25 kg/m\u0026sup2; vs. \u0026lt;25 kg/m\u0026sup2;).\u003c/p\u003e\n\u003cp\u003eSecondary outcomes will be analyzed using appropriate regression models depending on the outcome type (e.g., time-to-event analysis, competing risk models, logistic regression). Details on how missing data will be handled, as well as statistical models and sensitivity analysis, will be specified in the Statistical Analysis Plan, which will be finalized prior to database locking.\u003c/p\u003e\n\u003cp\u003eNo formal interim analysis for efficacy evaluation is planned, but a blinded review of enrollment progress and event accumulation will be conducted when 50% of the planned participants have been enrolled. This review will be conducted by the lead statistician without access to treatment assignment, and will not involve any hypothesis testing, to avoid influencing the final analysis. Specifically, this review will consider recruitment status, dropout rate, and the overall number of primary endpoint events observed in both treatment groups combined at 12 months post-enrollment.\u003c/p\u003e\n\u003ch2\u003ePowering and Sample Size\u003c/h2\u003e\n\u003cp\u003eThere are currently no established data on the incidence of infections at 12 months postoperatively in PD patients who have undergone exit-site creation with a silver CAPD catheter. Based on a previous study examining the efficacy of silver-mixed port used in totally implantable venous access ports [6], we set the relative risk for the primary endpoint of the silver CAPD catheters compared with that of conventional catheters at 0.5 (with event incidence rates of 0.4 for conventional catheters and 0.2 for silver CAPD catheters). Assuming a two-sided significance level of 5% and a power of 80%, the required sample size per group is 92 patients, equating to a total sample size of 184 when allocating patients in a 1:1 ratio between the silver CAPD catheter group and the conventional catheter group. Considering the design of this study, however, we anticipate that a certain number of cases will not proceed to final enrollment (exit-site creation) after allocation and will be excluded at the end of the enrollment period. Assuming that this proportion will be approximately 25%, the target sample size was set at 250 patients.\u003c/p\u003e\n\u003ch2\u003eEthics\u003c/h2\u003e\n\u003cp\u003eThe silver CAPD catheter has been certified by the Pharmaceuticals and Medical Devices Agency in Japan. Regulatory and ethical approval will be obtained from the Certified Review Board at each hospital. The ASCA-PD study will be conducted in accordance with the International Conference on Harmonization Good Clinical Practice guidelines and with the key principles of ethical conduct in research and the Declaration of Helsinki. The sponsor will not be involved with study design, or in data assembly and analysis.\u003c/p\u003e\n\u003ch2\u003eConfidentiality\u003c/h2\u003e\n\u003cp\u003ePersonal information about potential and enrolled participants will be collected, stored, and processed with strict safeguards to protect confidentiality before, during, and after the trial, in accordance with applicable data protection regulations. Each participant will be identified by a unique patient identification number, and a participant identification code list linking these numbers to personal information will be prepared and securely stored within the trial site. This list will not be disclosed outside the trial site.\u003c/p\u003e\n\u003cp\u003eWhen the results of the study are published, data will be presented in a manner that ensures individual participants cannot be identified. If a participant requests disclosure of retained personal information that can identify them, the principal investigator will, without undue delay, provide the relevant information to the participant. Upon request, the principal investigator will also disclose the study protocol and details of the study.\u003c/p\u003e\n\u003ch2\u003eData access\u003c/h2\u003e\n\u003cp\u003eAccess to the final trial dataset will be limited to the principal investigators and the study statistician. There are no contractual agreements that limit such access for the investigators.\u003c/p\u003e\n\u003ch2\u003eAncillary and post-trial care\u003c/h2\u003e\n\u003cp\u003eThis study will be conducted within the scope of standard health insurance coverage, with no off-label medications or uninsured tests used. In the event of a study-related health injury, appropriate treatment will be provided under the public health insurance system, and the Relief System for Adverse Drug Reactions may apply when relevant. The principal investigator will obtain both liability and compensation insurance to cover health injuries causally related to study participation.\u003c/p\u003e\n\u003ch2\u003eDissemination policy\u003c/h2\u003e\n\u003cp\u003eThe trial results will be presented at scientific meetings and published in peer-reviewed journals, and will also be reported to the jRCTs, typically within one year after the final results become available. Professional medical writers will not be used. The complete study protocol will be provided as a supplementary file.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAt the end of the 2021 fiscal year, approximately 340,000 patients were receiving dialysis treatment in Japan, with a prevalence of 2,786 per million population. This figure is significantly higher than in most European countries, where the prevalence is generally \u0026lt;1,000 per million population [11]. Most dialysis patients in Japan receive HD, with only 3.2% of the total dialysis population (approximately 10,000 patients) receiving PD. This proportion is strikingly lower than in regions such as Hong Kong and Thailand, where PD accounts for 23%\u0026ndash;72% of dialysis modalities, owing to the adoption of a PD-first policy [12, 13]. Approximately 272,000 patients with end-stage kidney disease undergo PD globally, representing around 11% of the total dialysis population [13].\u003c/p\u003e\n\u003cp\u003eOne of the primary reasons for the limited adoption of PD in Japan is the occurrence of PD-related infections such as ESI, TIs, and PD-associated peritonitis, leading to technique failure [14]. Preventive strategies for exit-site care, including the use of dressings and the application of topical antibiotic ointments, have been investigated to reduce PD-related infections [15-22]. The efficacy of dressings in preventing PD-related infections has not been demonstrated [15, 16] and the routine use of topical antibiotic ointments at catheter exit sites has not been widely adopted in Japan, mainly due to regulatory limitations regarding approved indications [23]. A recent systematic review and meta-analysis did not demonstrate significant effectiveness of mupirocin ointment in preventing ESI.[24], and the 2023 revision of the ISPD guidelines consequently downgraded the recommendation for the application of topical antibiotics at the exit site\u0026nbsp;[4]. There are currently no fully established guidelines for preventing PD-catheter exit-site infections.\u003c/p\u003e\n\u003cp\u003eThe antimicrobial effects of AgNPs have long been recognized. They have demonstrated broad-spectrum antimicrobial activity \u003cem\u003ein vitro\u003c/em\u003e [25, 26], and studies investigating the effectiveness of AgNP-coated PD catheters in preventing ESIs/TIs and PD-related peritonitis have been conducted in both animal and human subjects [27-30]. Although animal studies demonstrated their ability to prevent infections [27, 28], however, randomized controlled trials in humans failed to confirm the protective effects of AgNP-coated catheters or silver ring devices placed at the exit site [29, 30]. One possible reason for the lack of efficacy in humans was that the AgNP coating was only applied to the exterior of the catheter, and the duration of the antimicrobial effect of the AgNP coating was limited. In contrast, the silver PD catheter used in the current study incorporates AgNPs into the silicone material, allowing for a sustained antimicrobial effect on both the external and internal surfaces of the catheter.\u003c/p\u003e\n\u003cp\u003eThis study will examine the efficacy of silver CAPD catheters with incorporated AgNPs for preventing PD-related infections, particularly during the initiation phase of PD.\u003c/p\u003e"},{"header":"Trial status","content":"\u003cp\u003eThis manuscript was prepared based on Trial Protocol Version 1.1, dated February 14, 2025. Patient enrollment commenced on May 1, 2025, with a target of enrolling 250 patients by December 31, 2026. The first patient was enrolled on May 15, 2025.\u003c/p\u003e"},{"header":"List of abbreviations","content":"\u003cp\u003eAPD: automated peritoneal dialysis; CAPD: continuous ambulatory peritoneal dialysis; ESI: exit-site infection; HD: hemodialysis; ISPD: International Society for Peritoneal Dialysis; PD: peritoneal dialysis; SMAP: stepwise initiation of PD using Moncrief and Popovich; TI: tunnel infection\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAcknowledgments\u003c/p\u003e\n\u003cp\u003eWe sincerely appreciate the support provided for protocol development, research design planning, ethical and legal requirements review, and Certified Review Board application assistance by all members of the Institute for Clinical and Translational Science (iCATs) at Nara Medical University Hospital, including Prof. Masato Kasahara, Dr. Hiroyuki Kurakami, Dr. Kyouko Sakai, Dr. Kiyoshi Asada, Ryuzo Takashima, Yuriko Ito, Miu Kojima, and Mineko Yamaguchi. We also thank Susan Furness, PhD, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.\u003c/p\u003e\n\u003cp\u003eDisclosure Statement\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest related to this study. Fuji Systems Corporation provided technical support but had no role in the study design, data collection, analysis, interpretation, or manuscript preparation.\u003c/p\u003e\n\u003cp\u003eFunding Sources\u003c/p\u003e\n\u003cp\u003eThis study was supported by the Clinical Research Grant Program of Nara Medical University (Grant number: JHR2400003), the Public Research Grant from the Japanese Association of Dialysis Physicians (JADP Grant 2024-8), and operational funding provided by Fuji Systems Corporation to support the conduct of the clinical study.\u003c/p\u003e\n\u003cp\u003eAuthor Contributions\u003c/p\u003e\n\u003cp\u003eM.E. wrote the first draft of the paper and was involved in the study design. Y.I. had final responsibility for the decision to submit for publication. Y.I., H.Y., and M.Matsui contributed to the study concept and design and conducted the process evaluation. T.K., A.N., G.T., S.Ya., T.Sa., M.N., K.Ha., S.Ku., N.T., S.O., M.Mi., H.K., S.Ki., S.Ku., Y.S., K.Ha., M.M., T.Su., S.T., K.N., K.K., H.O., T.Ka., H.M., and T.Y. support trial management and coordination. KT is the trial Chief Investigator. All authors provided critical review of the manuscript for important intellectual content. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u003c/p\u003e\n\u003cp\u003eData sharing is not applicable to this study because no datasets were generated or analyzed; however, the study data will be made available upon reasonable request after completion of the trial.\u003c/p\u003e\n\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eThe study protocol and informed consent documents have been approved by the Certified Review Board, with Nara Medical University as the principal research institution (approval number: nara0065). Any important protocol modifications (e.g., changes to eligibility criteria, outcomes, or analyses) will be promptly communicated to all relevant parties, including the principal investigator, the research ethics committee, the Certified Review Board, the jRCTs, and the Ministry of Health, Labour and Welfare of Japan. Based on this approval, the study will be initiated at each participating site after obtaining implementation permission from the respective institutions.\u003c/p\u003e\n\u003cp\u003eWritten informed consent will be obtained from all study participants\u0026nbsp;by the site principal investigator or a sub-investigator, according to the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eConsent for publication is not applicable.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests. All researchers conducted this study as part of their academic research activities.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eUnited States Renal Data System. 2023 Annual Data Report. End Stage Renal Disease: Chapter 11 International Comparisons. 2023. https://usrds-adr.niddk.nih.gov/2023/end-stage-renal-disease/11-international-comparisons. Accessed May 30, 2024 2024.\u003c/li\u003e\n\u003cli\u003eKolesnyk I, Dekker FW, Boeschoten EW, Krediet RT. Time-dependent reasons for peritoneal dialysis technique failure and mortality. Perit Dial Int. 2010;30(2):170-7. doi:10.3747/pdi.2008.00277.\u003c/li\u003e\n\u003cli\u003eSakurada T, Kojima S, Yamada S, Koitabashi K, Taki Y, Matsui K et al. A multi-institutional, observational study of outcomes after catheter placement for peritoneal dialysis in Japan. Perit Dial Int. 2023;43(6):457-66. doi:10.1177/08968608231193240.\u003c/li\u003e\n\u003cli\u003eChow KM, Li PK, Cho Y, Abu-Alfa A, Bavanandan S, Brown EA et al. ISPD Catheter-related Infection Recommendations: 2023 Update. Perit Dial Int. 2023;43(3):201-19. doi:10.1177/08968608231172740.\u003c/li\u003e\n\u003cli\u003eNochaiwong S, Ruengorn C, Noppakun K, Panyathong S, Dandecha P, Sood MM et al. Comparative Effectiveness of Local Application of Chlorhexidine Gluconate, Mupirocin Ointment, and Normal Saline for the Prevention of Peritoneal Dialysis-related Infections (COSMO-PD Trial): a multicenter randomized, double-blind, controlled protocol. Trials. 2019;20(1):754. doi:10.1186/s13063-019-3953-8.\u003c/li\u003e\n\u003cli\u003eSuzuki T, Michimoto K, Hasumi J, Kisaki S, Hasegawa Y, Fujimori A et al. Silver-Mixed Port Reduces Venous Access Port Related Infection Rate Compared to Non-Silver-mixed Port: A Single-center Retrospective Analysis. Cardiovasc Intervent Radiol. 2023;46(12):1696-702. doi:10.1007/s00270-023-03583-y.\u003c/li\u003e\n\u003cli\u003eMoncrief JW, Popovich RP, Dasgupta M, Costerton JW, Simmons E, Moncrief B. Reduction in peritonitis incidence in continuous ambulatory peritoneal dialysis with a new catheter and implantation technique. Perit Dial Int. 1993;13 Suppl 2:S329-31. \u003c/li\u003e\n\u003cli\u003eEriguchi M, Tsuruya K, Yoshida H, Yamada S, Tanaka S, Suehiro T et al. Validation of the exit-site scoring system recommended by the 2005 guidelines of the International Society for Peritoneal Dialysis. Perit Dial Int. 2011;31(6):698-700. doi:10.3747/pdi.2010.00287.\u003c/li\u003e\n\u003cli\u003eLi PK, Chow KM, Cho Y, Fan S, Figueiredo AE, Harris T et al. ISPD peritonitis guideline recommendations: 2022 update on prevention and treatment. Perit Dial Int. 2022;42(2):110-53. doi:10.1177/08968608221080586.\u003c/li\u003e\n\u003cli\u003eHtay H, Cho Y, Pascoe EM, Darssan D, Nadeau-Fredette AC, Hawley C et al. Multicenter Registry Analysis of Center Characteristics Associated with Technique Failure in Patients on Incident Peritoneal Dialysis. Clin J Am Soc Nephrol. 2017;12(7):1090-9. doi:10.2215/CJN.12321216.\u003c/li\u003e\n\u003cli\u003eHanafusa N, Abe M, Joki N, Hoshino J, Wada A, Kikuchi K et al. Annual dialysis data report 2021, Japanese Society for Dialysis Therapy (JSDT) renal data registry. Renal Replacement Therapy. 2024;10(1):78. \u003c/li\u003e\n\u003cli\u003eChuengsaman P, Kasemsup V. PD First Policy: Thailand\u0026apos;s Response to the Challenge of Meeting the Needs of Patients With End-Stage Renal Disease. Semin Nephrol. 2017;37(3):287-95. doi:10.1016/j.semnephrol.2017.02.008.\u003c/li\u003e\n\u003cli\u003eLi PK, Chow KM, Van de Luijtgaarden MW, Johnson DW, Jager KJ, Mehrotra R et al. Changes in the worldwide epidemiology of peritoneal dialysis. Nat Rev Nephrol. 2017;13(2):90-103. doi:10.1038/nrneph.2016.181.\u003c/li\u003e\n\u003cli\u003eDavies SJ, Phillips L, Griffiths AM, Russell LH, Naish PF, Russell GI. What really happens to people on long-term peritoneal dialysis? Kidney Int. 1998;54(6):2207-17. doi:10.1046/j.1523-1755.1998.00180.x.\u003c/li\u003e\n\u003cli\u003eMushahar L, Mei LW, Yusuf WS, Sivathasan S, Kamaruddin N, Idzham NJ. Exit-Site Dressing and Infection in Peritoneal Dialysis: A Randomized Controlled Pilot Trial. Perit Dial Int. 2016;36(2):135-9. doi:10.3747/pdi.2014.00195.\u003c/li\u003e\n\u003cli\u003eTaheri S, Ahmadnia M, Mortazavi M, Karimi S, Reihani H, Seirafian S. Comparing the Effect of Dressing Versus No-dressing on Exit Site Infection and Peritonitis in Chronic Ambulatory Peritoneal Dialysis Patients. Adv Biomed Res. 2017;6:5. doi:10.4103/2277-9175.199263.\u003c/li\u003e\n\u003cli\u003eBernardini J, Bender F, Florio T, Sloand J, Palmmontalbano L, Fried L et al. Randomized, double-blind trial of antibiotic exit site cream for prevention of exit site infection in peritoneal dialysis patients. J Am Soc Nephrol. 2005;16(2):539-45. doi:10.1681/ASN.2004090773.\u003c/li\u003e\n\u003cli\u003eMcQuillan RF, Chiu E, Nessim S, Lok CE, Roscoe JM, Tam P et al. A randomized controlled trial comparing mupirocin and polysporin triple ointments in peritoneal dialysis patients: the MP3 Study. Clin J Am Soc Nephrol. 2012;7(2):297-303. doi:10.2215/CJN.07970811.\u003c/li\u003e\n\u003cli\u003eFindlay A, Serrano C, Punzalan S, Fan SL. Increased peritoneal dialysis exit site infections using topical antiseptic polyhexamethylene biguanide compared to mupirocin: results of a safety interim analysis of an open-label prospective randomized study. Antimicrob Agents Chemother. 2013;57(5):2026-8. doi:10.1128/AAC.02079-12.\u003c/li\u003e\n\u003cli\u003eNunez-Moral M, Sanchez-Alvarez E, Gonzalez-Diaz I, Pelaez-Requejo B, Fernandez-Vina A, Quintana-Fernandez A et al. Exit-site infection of peritoneal catheter is reduced by the use of polyhexanide. results of a prospective randomized trial. Perit Dial Int. 2014;34(3):271-7. doi:10.3747/pdi.2012.00109.\u003c/li\u003e\n\u003cli\u003eTam BM, Chow SK. A preliminary report on the effectiveness of nanotechnology anti-microbial spray dressing in preventing Tenckhoff catheter exit-site infection. Perit Dial Int. 2014;34(6):670-3. doi:10.3747/pdi.2013.00199.\u003c/li\u003e\n\u003cli\u003eZhang L, Badve SV, Pascoe EM, Beller E, Cass A, Clark C et al. The Effect of Exit-Site Antibacterial Honey Versus Nasal Mupirocin Prophylaxis on the Microbiology and Outcomes of Peritoneal Dialysis-Associated Peritonitis and Exit-Site Infections: A Sub-Study of the Honeypot Trial. Perit Dial Int. 2015;35(7):712-21. doi:10.3747/pdi.2014.00206.\u003c/li\u003e\n\u003cli\u003eIto Y, Ryuzaki M, Sugiyama H, Tomo T, Yamashita AC, Ishikawa Y et al. Peritoneal Dialysis Guidelines 2019 Part 1 (Position paper of the Japanese Society for Dialysis Therapy). Renal Replacement Therapy. 2021;7(1). doi:10.1186/s41100-021-00348-6.\u003c/li\u003e\n\u003cli\u003eObata Y, Murashima M, Toda N, Yamamoto S, Tsujimoto Y, Tsujimoto Y et al. Topical application of mupirocin to exit sites in patients on peritoneal dialysis: a systematic review and meta-analysis of randomized controlled trials. Renal Replacement Therapy. 2020;6(1). doi:10.1186/s41100-020-00261-4.\u003c/li\u003e\n\u003cli\u003eLara HH, Garza-Trevino EN, Ixtepan-Turrent L, Singh DK. Silver nanoparticles are broad-spectrum bactericidal and virucidal compounds. J Nanobiotechnology. 2011;9:30. doi:10.1186/1477-3155-9-30.\u003c/li\u003e\n\u003cli\u003ePatel V, Berthold D, Puranik P, Gantar M. Screening of cyanobacteria and microalgae for their ability to synthesize silver nanoparticles with antibacterial activity. Biotechnol Rep (Amst). 2015;5:112-9. doi:10.1016/j.btre.2014.12.001.\u003c/li\u003e\n\u003cli\u003eDasgupta M. Autochthonous bacterial spread from catheter exit site is reduced by silver catheter. Perit Dial Int. 1995;15:S49. \u003c/li\u003e\n\u003cli\u003eFung LC, Khoury AE, Vas SI, Smith C, Oreopoulos DG, Mittelman MW. Biocompatibility of silver-coated peritoneal dialysis catheter in a porcine model. Perit Dial Int. 1996;16(4):398-405. \u003c/li\u003e\n\u003cli\u003ePommer W, Brauner M, Westphale HJ, Brunkhorst R, Kramer R, Bundschu D et al. Effect of a silver device in preventing catheter-related infections in peritoneal dialysis patients: silver ring prophylaxis at the catheter exit study. Am J Kidney Dis. 1998;32(5):752-60. doi:10.1016/s0272-6386(98)70130-1.\u003c/li\u003e\n\u003cli\u003eCrabtree JH, Burchette RJ, Siddiqi RA, Huen IT, Hadnott LL, Fishman A. The efficacy of silver-ion implanted catheters in reducing peritoneal dialysis-related infections. Perit Dial Int. 2003;23(4):368-74. \u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003ch2\u003eTable 1 Inclusion and exclusion criteria\u003c/h2\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"1021\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 436px;\"\u003e\n \u003cp\u003eInclusion criteria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 585px;\"\u003e\n \u003cp\u003eExclusion criteria\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 436px;\"\u003e\n \u003cp\u003e\u0026bull; Participants aged 18 years or over at the date of screening\u003cbr\u003e\u0026nbsp;\u0026bull; Incident patients initiating PD according to a pre-planned schedule\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 585px;\"\u003e\n \u003cp\u003e\u0026bull; Patients reinitiating PD after kidney transplantation or hemodialysis\u003cbr\u003e\u0026nbsp;\u0026bull; Patients scheduled to have the exit site created outside the upper or lower abdomen\u003cbr\u003e\u0026nbsp;\u0026bull; Patients with a history of metal allergy (including silver)\u003cbr\u003e\u0026nbsp;\u0026bull; Patients with an expected life expectancy of less than one year at the time of PD initiation (e.g., patients with terminal cancer)\u003cbr\u003e\u0026nbsp;\u0026bull; Patients with severe liver cirrhosis (Child-Pugh class C)\u003cbr\u003e\u0026nbsp;\u0026bull; Patients with dermatological conditions such as psoriasis vulgaris or atopic dermatitis\u003cbr\u003e\u0026nbsp;\u0026bull; Patients with a gastrostomy or colostomy\u003cbr\u003e\u0026nbsp;\u0026bull; Patients receiving immunosuppressive therapy (including oral and/or intravenous corticosteroids)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003ePD: peritoneal dialysis\u003c/p\u003e\n\u003cp\u003eTable 2 is available in the Supplementary Files section.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eTable 3 Primary and secondary outcomes\u003c/h2\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"989\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 989px;\"\u003e\n \u003cp\u003ePrimary outcome\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 989px;\"\u003e\n \u003cp\u003e\u0026nbsp; Composite endpoint of all exit-site and tunnel infections occurring within 12 months after PD initiation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 989px;\"\u003e\n \u003cp\u003eSecondary outcomes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 989px;\"\u003e\n \u003cp\u003e1. All exit-site and tunnel infections occurring within 12 months after PD initiation, with catheter removal unrelated to infection and death treated as competing events\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 989px;\"\u003e\n \u003cp\u003e2. First occurrence of exit-site or tunnel infection within 12 months after PD initiation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 989px;\"\u003e\n \u003cp\u003e3. First occurrence of exit-site or tunnel infection within 12 months after PD initiation, with catheter removal unrelated to infection and death treated as competing events\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 989px;\"\u003e\n \u003cp\u003e4. All exit-site and tunnel infections occurring within 30 days after PD initiation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 989px;\"\u003e\n \u003cp\u003e5. All episodes of peritonitis occurring after catheter insertion\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 989px;\"\u003e\n \u003cp\u003e6. Catheter removal of any cause after insertion\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 989px;\"\u003e\n \u003cp\u003e7. Composite of PD-related infections requiring surgical intervention*\u003csup\u003e1\u003c/sup\u003e, and death within 30 days due to peritonitis after catheter insertion\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 989px;\"\u003e\n \u003cp\u003e8. Catheter patency*\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 989px;\"\u003e\n \u003cp\u003e9. Allergic reactions such as contact dermatitis, eosinophilia, and eosinophilic peritonitis after catheter insertion\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 989px;\"\u003e\n \u003cp\u003e10. Refractory and recurrent exit-site/tunnel infections and peritonitis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 989px;\"\u003e\n \u003cp\u003e11. Presence of colonization at the exit site and culture results at the end of the observation period*\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 989px;\"\u003e\n \u003cp\u003e12. Technique failure*\u003csup\u003e4\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 989px;\"\u003e\n \u003cp\u003e13. Transition from peritoneal dialysis to hybrid therapy (combination of HD and PD)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*\u003csup\u003e1\u003c/sup\u003ePD-related infections requiring surgical intervention are defined as catheter removal, relocating exit site, unroofing, and cuff shaving for subcutaneous cuff extrusion\u003c/p\u003e\n\u003cp\u003e*\u003csup\u003e2\u003c/sup\u003eCatheter patency is defined as the absence of catheter tip migration or suboptimal placement, tubing kinks, omental wrapping, fibrin/blood clots, preexisting adhesions, obstruction by epiploic appendices or uterine tubes, pericatheter hernia, and intractable drain pain due to excessively deep pelvic catheter tip placement.\u003c/p\u003e\n\u003cp\u003e*\u003csup\u003e3\u003c/sup\u003eTwelve months after PD initiation or at the time of catheter removal within 12 months\u003c/p\u003e\n\u003cp\u003e*\u003csup\u003e4\u003c/sup\u003eTechnique failure was defined as transition to hemodialysis for \u0026ge;30 days or death, excluding kidney transplantation.\u003c/p\u003e\n\u003cp\u003ePD: peritoneal dialysis, HD: hemodialysis\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"trials","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"trls","sideBox":"Learn more about [Trials](http://trialsjournal.biomedcentral.com/)","snPcode":"13063","submissionUrl":"https://www.editorialmanager.com/trls","title":"Trials","twitterHandle":"MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Silver CAPD catheter, PD-related infections, Exit-site infection, PD-related peritonitis, Peritoneal dialysis, Prevention, Randomized controlled trial","lastPublishedDoi":"10.21203/rs.3.rs-6857752/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6857752/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground:\u003c/p\u003e\n\u003cp\u003ePeritoneal dialysis (PD) offers greater flexibility than hemodialysis, especially in patients with limited mobility or demanding schedules; however, PD-related infection is a major complication and a cause of withdrawal from peritoneal dialysis. The Antibiotic effect of Silver continuous ambulatory peritoneal dialysis (CAPD) Catheter on Peritoneal Dialysis-related infections (ASCA-PD) study will evaluate the effectiveness of a novel silver CAPD catheter, incorporating silver-based antimicrobial technology, for preventing these infections and improving PD adherence.\u003c/p\u003e\n\u003cp\u003eMethods/Design:\u003c/p\u003e\n\u003cp\u003eThis randomized, open-label, parallel-group, multicenter trial will evaluate the efficacy and safety of a silver CAPD catheter compared with those of a conventional catheter at 14 Japanese facilities. A total of 250 adult patients with newly initiated PD will be enrolled and randomized 1:1 to receive either catheter type. The key exclusion criteria are prior PD, emergency PD initiation, non-abdominal exit-site placement, metal allergy, life expectancy \u0026lt;1 year, severe liver disease, certain dermatologic conditions, and immunosuppression. After providing informed consent, patients will undergo nasal swab screening for methicillin-resistant \u003cem\u003eStaphylococcus aureus\u003c/em\u003e. Randomization will be stratified by facility and diabetes status. The primary outcome is the composite endpoint of all exit-site and tunnel infections within 12 months of PD initiation. Secondary outcomes include individual infection events, catheter removal, peritonitis, catheter patency, allergic reactions, technique failure (transition to hemodialysis for ≥30 days or death), and transition to hybrid dialysis. A Poisson regression model will be used to analyze the primary outcome, adjusting for observation time, treatment group, and stratification factors. Time-to-event secondary outcomes will be analyzed by competing risk regression. Subgroup analyses will be carried out to explore the impacts of age, sex, diabetes, insertion method, and body mass index.\u003c/p\u003e\n\u003cp\u003eDiscussion:\u003c/p\u003e\n\u003cp\u003eUnlike previous designs, our silver CAPD catheter incorporates AgNPs into silicone, enabling sustained antimicrobial effects both externally and internally, potentially overcoming limitations seen in prior human studies. This study will demonstrate the efficacy of silver CAPD catheters for preventing PD-related infections, especially during the initiation phase of PD, with the aim of providing a new therapeutic option.\u003c/p\u003e\n\u003cp\u003eTrial registration:\u003c/p\u003e\n\u003cp\u003eJapan Registry of Clinical Trials, jRCTs052250003. Registered on April 4, 2025.\u003c/p\u003e","manuscriptTitle":"The Antibiotic effect of Silver CAPD Catheter on Peritoneal Dialysis-related infections (ASCA-PD) study: a multicenter randomized open-label trial protocol","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-27 11:01:34","doi":"10.21203/rs.3.rs-6857752/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2025-09-28T17:03:56+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-19T06:54:42+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-17T09:03:47+00:00","index":"","fulltext":""},{"type":"submitted","content":"Trials","date":"2025-08-15T11:48:56+00:00","index":"","fulltext":""},{"type":"decision","content":"Major revision","date":"2025-07-24T03:08:07+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"trials","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"trls","sideBox":"Learn more about [Trials](http://trialsjournal.biomedcentral.com/)","snPcode":"13063","submissionUrl":"https://www.editorialmanager.com/trls","title":"Trials","twitterHandle":"MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f1a08884-6e99-4dbb-b17e-aca5ae419cd7","owner":[],"postedDate":"August 27th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-12-22T16:06:49+00:00","versionOfRecord":{"articleIdentity":"rs-6857752","link":"https://doi.org/10.1186/s13063-025-09250-6","journal":{"identity":"trials","isVorOnly":false,"title":"Trials"},"publishedOn":"2025-12-17 15:58:33","publishedOnDateReadable":"December 17th, 2025"},"versionCreatedAt":"2025-08-27 11:01:34","video":"","vorDoi":"10.1186/s13063-025-09250-6","vorDoiUrl":"https://doi.org/10.1186/s13063-025-09250-6","workflowStages":[]},"version":"v1","identity":"rs-6857752","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6857752","identity":"rs-6857752","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}