Hemospray® (Hemostatic powder TC-325) as monotherapy for acute gastrointestinal bleeding: a multi-center prospective study

Hemospray® (Hemostatic powder TC-325) as monotherapy for acute gastrointestinal bleeding: a multi-center prospective study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Hemospray® (Hemostatic powder TC-325) as monotherapy for acute gastrointestinal bleeding: a multi-center prospective study Apostolis Papaefthymiou, Nasar Aslam, Mohamed Hussein, Durayd Alzoubaidi, and 30 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3923533/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Topical hemostatic powders are a reliable second-line approach in acute gastrointestinal (GI) bleeding (AGIB) treatment, according to the existing guidelines. Increasing evidence supports the use of hemostatic powder TC-325 (Hemospray®) as monotherapy in specific GI bleeding scenarios. This prospective, multi-center study evaluated the performance of TC-325 as monotherapy for GI hemorrhage. Methods Eighteen centres across Europe, and USA contributed between 2016 and 2022 to an international multicentre prospective registry. Adults with AGIB were eligible (melena, hematemesis, hematochezia, Glasgow-Blatchford score ≥ 1 or abnormal Oakland score), unless TC-325 was part of combined hemostasis (adjunctive to clips or thermocautery). The primary endpoint was immediate haemostasis. Secondary outcomes were rebleeding, 7- and 30-day mortality rates. Potential associations with risk factors were investigated with statistical significance set for p ≤ 0.05. Results One hundred and ninety patients were included (age range = 51–81, male:female = 2:1). Peptic ulcer (n = 48), upper GI malignancy (n = 79), post endoscopic treatment-related hemorrhage (n = 37), and lower GI lesions (n = 26) were diagnosed. The primary outcome was recorded in 96.3% (95%CI:92.6–98.5) with rebleeding in 17.4% (95%CI:11.9–24.1) when TC-325 was used as primary monotherapy. Post-hemostasis, 9.9% (95%CI:5.8–15.6) died within 7 days and 21.7% (95%CI:15.6–28.9) within 30 days. Regarding peptic ulcer, the immediate hemostasis was achieved in 88% (95%CI:75–95) and 26% (95%CI:13–43) rebled. Increased American Society of Anaesthesiologists (ASA) score was associated with mortality [OR:23.5 (95%CI:1.60–345); p = 0.02]. The primary outcome was achieved in 100% of cases with malignancy and post GI intervention bleeding, with rebleeding in 17% and 3.1%, respectively. Twenty-six patients received Hemospray® for lower GI bleeding, and in all but one the primary outcome was achieved. Conclusions TC-325 powder as monotherapy represents a safe and effective modality especially in malignancy- or post-endoscopic intervention-related bleeding. In peptic ulcer bleeding it could be helpful when the standard of care treatment is not feasible or unavailable, to stabilise patients. Hemospray® TC-325 Endoscopy Upper Gastro-intestinal bleeding Hemospray monotherapy Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Acute gastrointestinal bleeding (AGIB) is a common medical emergency, especially in the era of the broadly used antithrombotic agents. 1 , 2 Depending on the origin of the bleeding, AGIB is defined as upper GIB (UGIB), when located proximally to the ligament of Treitz, and lower GIB (LGIB) when it occurs elsewhere in the alimentary tract. The frequency of UGIB follows a reducing trend over the last two decades, probably due to the eradication of Helicobacter pylori and the broad prescription of proton pump inhibitors (PPIs). 3 More specifically, UGIB is recorded at a rate of 67 cases per 100,000 population in the United States of America 4 134 per 100,000 population in the UK 5 and 47 per 100,000 in Spain. 3 Similarly, the incidence of UGIB-related deaths has reduced, as indicated by a database study of peptic ulcer bleeding from the US, conducted between 1989 and 2009, which found that the mortality rate had halved, falling from 4.5 to 2.1%. 6 Although LGIB is more common than UGIB, limited data exist in the literature regarding its prevalence in the general population. Interestingly, the rate of diverticular disease and angiodysplasia-related bleeding has increased, probably reflecting the use of antiplatelets and oral anticoagulants. 1 , 2 Endoscopic hemostasis represents the mainstay treatment alongside optimisation of medical care. This is supported by studies revealing a reduction in overall mortality caused by GI bleeding. Gastrointestinal Endoscopy Societies have published thorough guidelines on the management of AGIB, favouring dual hemostasis as the optimal approach in cases of active hemorrhage. 7 – 9 Mechanical treatment, including a variety of endoscopic clips and bands, provides a reliable and lasting effect, especially when applied to focal lesions and vessels. Similarly, thermal ablation techniques target actively bleeding or high-risk spots with equivalent efficacy. Injection with adrenaline solution provides a combined tamponade and vasoconstritive effect, however it is limited by the short duration and needs to be accompanied with another technique. 9 These techniques require fine movements to target the bleeding site, which may be challenging in difficult positions or when there is a large abnormal surface, such as malignancies. Combination therapy, including at least two of the aforementioned modalities is strongly recommended by current guidelines and supported by high quality evidence. 8 , 9 Although the available modalities offer an adequate effect on hemostasis, single treatment with epinephrine injection is inferior to combination therapies with thermal or mechanical hemostasis. At least in cases with active bleeding, epinephrine injection in the bleeding site followed by cauterization or clipping provides lower rates of rebleeding and need for emergency surgery. 10 , 11 However, in cases with hard and unstable endoscopic position, unavailability of sophisticated devices, such as over-the-scope clips, and inadequate endoscopic experience, combined hemostasis can be impossible. Topical hemostatic powders offer a treatment modality that is easy to use with a minimal learning curve. Therefore, they provide a promising alternative, especially when a targeted treatment cannot be provided. Additional benefits include the ability to treat a large surface area and their non-contact nature. TC-325 (Hemospray®; Cook Medical, Winston-Salem, North Carolina, USA) is a mineral-based hygroscopic powder that is deployed using a pressurised carbon dioxide cannister. ( Fig. 1 ) When Hemospray® comes into direct contact with blood it triggers a clotting cascade which results in the formation of a coagulum. This leads to a tamponade effect over the bleeding foci by forming an adhesive seal which results in hemostasis. The powder then sloughs off the mucosa over the proceeding 24–72 hours. 12 Althought these hemostatic agents seem to yield an acceptable rate of bleeding cessation, they are currently recommended as rescue theraphy as opposed to primary theraphy. The aim of this single-arm, prospective, multi-centre international registry study was to evaluate hemostasis outcomes and adverse events in consecutive patients who received Hemospray® as endoscopic monotherapy for AGIB, in various locations and with different underlying causes. Methods Study design A prospective international multi-center study was conducted, in form of a registry, to investigate the efficacy of Hemospray® on AGIB as monotherapy. The Hemospray® Registry was presented to the local research ethics committee (London-South East Research Ethics Committee) and received ethical approval in October 2016. (ISRCTN29594250). A total of 18 centres across 3 continents (Europe, USA, Australia) have contributed to the registry between January 2016 – February 2022. The study protocol conformed to the ethical guidelines of the last revision of Declaration of Helsinki and complied with Good Clinical Practice Guidelines. 13 , 14 Patients' anonymity was ensured and all of recruited subjects provided a written informed consent for their participation in this trial. Inclusion criteria Adult patients with evidence of AGIB were considered as eligible to undergo endoscopic hemostasis with TC-325. UGIB was suspected in patients with melena, hematemesis or Glasgow-Blatchford score ≥ 1. Cases with hematochezia and abnormal Oakland score were treated as LGIB, unless evidence of UGIB existed (e.g. increased urea, hemodynamic instability). The final decision for enrollment was at the endoscopists’ discretion during the endoscopy. Regarding peptic ulcers, only cases with active bleeding in endoscopy were recruited (Forrest Type 1a and Type 1b). Patients were excluded if they did not consent to participate in the study, had prior failed attempts for hemostasis on the same or previous session, or when TC-325 was used as part of combined hemostasis (adjunctive to clips or thermocautery). Procedure Following rescusitation with intravenous fluids and personalised medical treatment, where needed (e.g. PPIs, red-blood cells transfusion), upper or lower GI endoscopy was offered depending on the suspected area of bleeding. Upon the identification of the bleeding site, TC-325 was sprayed on the lesion, using the commercially available system (Hemospray®; Cook Medical, Winston-Salem, North Carolina, USA). This system includes a canister filled with the powder, a 7 or 10Fr delivery catheter, and a CO 2 pump incorporated to a handle controlling the propulsion of the powder. After obtaining a clear field in front of the bleeding site, the working channel of the endoscope was dried with air inflation, followed by the catheter insertion at 1-2cm from the bleeding lesion. Short bursts were performed to release the powder under direct vision until the area was completely covered by the powder. The site was then observed for at least five minutes to assess for immediate hemostasis or the need for complementary treatment. Data collection A predefined online platform was used to insert and keep the records of the enrolled cases, including the variables that were analyzed. Only the primary investigators (NA, RJH) had access to the patients’ records across centers. Outcomes and definitions Given the different behaviour and impact of the potential bleeding causes and the challenges raised by the location, the outcomes were measured depending on the cause (e.g. peptic ulcer, malignancy, iatrogenic bleeding) and the bleeding site (upper or lower GI) in order to identify any potential benefit from TC-325 related to these variables. The primary endpoint was defined as the rate of immediate endoscopic hemostasis using the Hemospray® device. This was defined as the intraprocedure observation of bleeding cessation within the first 5 minutes post monotherapy with TC-325, without recurrence on the same session. The 5 minutes threshold was also used in previous studies, representing a reasonable comparator. 15 Rebleeding rates, diagnosed when clinical hemorrhage was observed (new hematemesis or melena associated with hemodynamic change following index treatment) or drop in haemoglobin > 2g/L, were considered as a secondary outcome. 16 , 17 Moreover, 7- and 30-day all cause mortality rates were calculated. As for any interventional procedure, the frequency and the severity of adverse events were also evaluated. Follow-up A 30 days follow up was agreed, either with a face-to-face clinic review or telephone consultation, to assess for recurrence or adverse events. Statistical analysis Data analysis was performed using the Statistical Package for Social Science Software for Windows (IBM SPSS Statistics, Version 28.0. Armonk, NY: IBM Corp). Continuous variables are presented as mean (± standard deviation; SD) and categorical variables are shown as percentages. We examined the association between the recorded independent variables and the outcomes. Logistic regression was performed in two stages. Firstly, association between each factor and outcomes was examined separately as a univariable analysis. If several factors showed a statistically significant association with the primary outcomes, we then examined the joint association between the factors as part of a multivariable analysis. Where appropriate we adopted a backwards stepwise selection procedure to omit non-significant variables from the final model. Odds ratios (OR) and their 95% confidence intervals (CIs) were derived from each variable coefficient in the final model. Statistical significance was considered for P values ≤ 0.05 (two tailed). Results One hundred and ninety patients were finally included in our cohort and received TC-325 as monotherapy between January 2016 and February 2022. The age ranged between 51 and 81 years with median being 66–71 years among subgroups, and the male to female ratio was 2:1. Immediate hemostasis was yielded in 96.3% (95%CI: 92.6–98.5; 183/190) of patients with an overall recurrence rate of 17.4% (95%CI: 11.9–24.1; 28/161). Sixteen out of 161 patients [9.9% (95%CI: 5.8–15.6)] died withing 7 days post-hemostasis with this outcome raised to 21.7% (95%CI: 15.6–28.9; 35/161) after one month. Four subgroups were identified, including cases with bleeding peptic ulcer (n = 48), upper GI malignancy (n = 79), post endoscopic treatment-related hemorrhage (n = 37), and lower GI lesions (n = 26). Table 1 depicts the main information of these subgroups. Peptic ulcer related bleeding Forty eight patients with Forrest Ia or Ib ulcer were included out of a total 74 cases with ulcer related bleeding ( Fig. 2 ). The rationale for Hemospray in this seting is that once it comes into contact with blood it forms a cohesive and adhesive barrier that tamponades the bleeding lesion. This subsequently promotes the concentration of clotting factors and cellular elements that may activate the clotting cascade. 18 In our cohort, immediate hemostasis was achieved in 42/48 patients equating to a rate of 88% (95%CI:75–95). (Table 2) The Blatchford score was borderline associated with failed haemostasis; every 5-unit increase in the score resulted in an increasing odd of failure by 5-fold (p = 0.05). The secondary outcomes (Table 2) were assessed in 38 patients who attended follow-up. Rebleeding was observed in 26% (95%CI:13–43; 10/38) of cases. After the index hemostasis, seven patients died within 7 days [11% (95%CI:3–25)] and 10 patients within 30 days [26% (95%CI:13–43; 10/38). Univariate analysis showed an increased ASA score was associated with 30-day mortality. Mortality was 6% in patents with an ASA grade 1–2 compared to 44% with an ASA grade 4–5. The odds of death were 12 times higher for patients with higher ASA grades (p = 0.03), and the significance was preserved on multivariable analysis [OR: 23.5 (95%CI:1.60–345); p = 0.02]. Upper GI malignancy Seventy-nine patients with an upper GI cancer were recruited in this subgroup (19 esophagus, six esophagogastric junction, 51 gastric, three duodenal). The primary outcome was achieved in 100% (79/79) of upper GI malignancy cases, regardless of the location or lesion size. ( Fig. 3 ) Rebleeding after primary hemostasis was observed in 12 patients [17% (95%CI:9–28)] among 69 patients who had follow-up information available. The median tumour size was 30mm (IQR: 19–50) and there was a tendency for rebleeding among lesions > 40mm (27% vs 10%), albeit non-significant (p = 0.09). The mortality rate after primary hemostasis among those followed-up (N = 69) was 7% (95%CI:2–16; 5/69) within seven days, and 25% (95% CI:15–36; 17/69) within 30 days. Hemodynamic instability was associated with a 9-fold increased 30-day mortality compared to those with hemodynamic stability [OR:8.89 (95%CI:1.58–49.9); p = 0.01]. Post Upper GI endoscopic therapy Post-procedure bleeding was diagnosed and treated with TC-325 after various procedures, as presented in Fig. 4 . An optimal rate of immediate hemostasis was achieved [100% (95%CI:91–100); 37/37], for all of the different procedures. Only one case of endoscopic mucosal resection (EMR) [3.1% (95%CI:0–16); 1/32] presented with rebleeding, with the defect been 50mm and the resected lesion 22.5mm. One patient died within the first seven and thirty days [3.1% (95%CI:0–16); 1/32]. Lower GI bleeding A total of 26 patients received Hemospray® for LGIB, and in all but one the primary outcome was achieved [96%(95%CI:80–100); 25/26]. Follow-up information was available in 22 cases with a rebleeding rate of 23% (95%CI:8–45; 5/22). The univariable analysis revealed that age and hemodynamic status were significantly associated with rebleeding. More specifically, for every 10-year increase in age the risk of rebleeding was reduced by 5-fold (p = 0.03), whereas it was 18 times higher in patients who were hemodynamically unstable when compared to those who were hemodynamically stable (p = 0.04). Post-hemostasis, mortality was 14% (95%CI:3–35; 3/22) within the first seven days and 32% (95% CI: 14–55%; 7/22) within the first 30 days; none of the factors included in our regression models was linked with 30-day mortality. Adverse Events A single complication was reported in the registry with the endoscopist reporting catheter blockage during the treatment of a duodenal ulcer. Despite this, immediate hemostasis was achieved and there were no reports of rebleeding. Discussion This prospective multi-center registry assessed the efficacy of Hemospray® as monotherapy. Immediate hemostasis was achieved in 88–100% across a range of GI bleeding scenarios. The highest rates were recorded in malignancy and post-endoscopic intervention related bleeding, where TC-325 was universally successful. Interestingly, these two subgroups were associated with the lowest rates of recurrent hemorrhage (17% and 3.1%, respectively), whereas one fourth of peptic ulcers and LGI lesions rebled. A recent meta-analysis assessed the pooled rates of 19 studies, including 212 cases where Hemospray® was used as monotherapy. Their outcomes were similar to ours with an immediate hemostasis rate of 91% (95%CI: 79–96), regardless the combined use with other modalities, the intensity of bleeding, and its cause. The early rebleeding rate was 21% (95%CI; 14–31), which is higher than the 17.4% (95%CI:11.9–24.1) observed in our registry across all scenarios. 19 Within the first month after hemostasis, the mortality among patients treated for a peptic ulcer or upper GI malignancy was 25%, which was higher among those with an advanced ASA score or haemodynamic instability. Only one patient died post-EMR, whereas the higher mortality rates were detected among patients with LGIB, however none of the evaluated variables was associated with this outcome. Finally, TC-325 monotherapy was an extremely safe treatment with only once adverse event reported secondary to catheter blockage. In 2023, a Field Safety Notice was released regarding adherence of the endoscope to the haemostatic powder while deployed in a retroflexed position, but this was not seen in the registry. Treating active peptic ulcer-related bleeding requires at least two hemostatic techniques with hemostatic powders, such as TC-325, considered for refractory or recurrent cases. 9 Hemospray® monotherapy yielded bleeding cessation in 88% (95%CI:75–95) of cases, however the recurrence rate was considerable [26% (95%CI:13–43)], accompanied with a similarly high mortality rate within the first month [26% (95%CI:13–43)]. Interestingly, the increasing ASA score, reflecting the patients’ comorbidities and perioperative risk, was an independent predictor of mortality with an OR: 23.5. We have previously shown among 202 patients who received Hemospray® monotherapy (25%), combination therapy (75%) or Hemospray® rescue therapy (25%), that the overall rate of hemostasis is 88%, without difference among subgroups. Similarly, there was no difference in rebleeding rates (17%) and early mortality (12%), however the one-month mortality rates were significantly lower when a combined hemostasis approach was applied compared to monotherapy (p < 0.001). 15 Despite the theoretical risk of failure and rebleeding in cases with spurting hemorrhage (Forrest Ia), it is not homogenously supported by the literature. 15 , 20 The high rates of immediate hemostasis and the non-inferiority compared to the combined approach for this outcome, reveal a significant role for TC-325 in achieving a direct effect on the active bleeding site, especially when combined hemostasis cannot be achieved, as happens in difficult position, marginally stable patients, or unclear field. Hemospray® could be used in these cases as a bridge therapy, in order to gain time with primary control before a second look endoscopy, especially when resources are limited, or when the patient needs to be transferred to another center for definitive treatment. However, the significantly higher rates of mortality in monotherapy cases with comorbidities imply the need for confirmation of hemostasis with a second endoscopy and complementary treatment where needed. Potential causes associated with these rates need to be assessed by future studies, thereby evaluating the clinical approach policies post-hemospray monotherapy for peptic ulcer, including restarting feeding, transfusion policy and antithrombotics continuation. Malignancy related bleeding is notoriously difficult to treat given the lack of direct target for endotherapy, the tumour tissue friability, the diffuse bleeding and the absence of a sinlge bleeding vessel. 19 , 21 The wide field of treatment during the application of Hemospray makes it a helpful endoscopic option for this indication, 21 and we have shown immediate hemostasis is achieved in 100% of the cases. Similar studies provide equivalent results regarding immediate efficacy. 22 – 24 Additionally, TC-325 reduces significantly the required transfusions in this patients group. 24 A recent RCT randomized 106 patients with malignancy GI bleeding to receive monotherapy with Hemospray® or the standard treatment (thermal or mechanical modalities or adrenaline injection alone or in combination). Immediate hemostasis rate was significantly higher using Hemospray® compared to the conventional techniques (100% vs 68.6% respectively; p < 0.001) and, more interestingly, the recurrence rates were lower in the Hemospray® group as well (2.1% vs 21.3%; p = 0.003). However, we should note that up to 20% of the standard treatment cohort were managed with ephinephrine therapy alone. 25 In our cohort, rebleeding occurred in 17% of cases with lesions larger than 4cm presenting a non-significant tendency for recurrence, however data on variables affecting this outcome (e.g. morphology, location of the lesion, coagulation status) need to be elucidated by future studies. Considering mortality, a low number of patients (7%) died during the first week, though this rate was increased within a month, especially among patients who presented with hemodynamic instability. This outcome shows heterogeneity in the literature ranging between 18.9–44.9% within 30-days post bleeding, with active bleeding during the endoscopy increasing the risk of death by 2.24. 26 , 27 Another field, where Hemospray® could represent a reliable choice as monotherapy is post-endoscopic intervention bleeding. In our cohort, the immediate hemostasis was yielded in all of bleeding cases with only one patients presenting with recurrence. This single case occurred following colonic EMR where the lesion was 50mm in size. 28 Similar results of optimal hemostasis are also presented by our group in a relative study, with recurrencies occurring in two post-EMR patients out of fifty-seven (4%). 29 Data on the performance of Hemospray® in LGIB is limited, however it appears equivalent to UGIB. 19 Although immediate bleeding cessation was achieved in almost all of our patients, the recurrence rate was relatively high [23% (95%CI:8–45%)], probably reflecting a persistent LGIB etiology in most cases, such as diverticular disease. Finally, TC-325 is already established in terms of safety, with the most common adverse event being the catheter blockage. The most significant limitation of this multi-centre prospective registry study is that of its non-randomised design with no comparator. Patient selection for monotherapy use was at the discretion of the endoscopist as opposed to a set criteria/protocol which has potentially introduced an element of selection bias. Furthermore, excluding patients who underwent combination therapy with other endoscopic modalities could influence the true efficacy of Hemospray® monotherapy. This is because initial use with a hemostatic powder may have required salvage intervention during the same procedure. Moreover, detailed aspects regarding macroscopic features of bleeding lesions or histological diagnosis regarding malignancy were not extracted which could have impacted our outcome measures. A significant drawback is the fact that the exact cause of death for patients was not documented, meaning that we cannot directly attribute rebleeding or immediate hemostasis to mortality. Endoscopic hemostasis using the TC-325 powder as monotherapy is safe and effective, especially in hemorrhage due to malignant lesions or post-endoscopic intervention. ( Fig. 5 ) In peptic ulcer-related bleeding it could achieve immediate results when the combined standard of care treatment is not feasible. This enables more time to optimise patients’ condition and make a definite plan. In these cases, a second look endoscopy could be considered to confirm the outcome and intervene when necessary, however this approach should be further evaluated. Key Findings Established knowledge TC-325 represents a safe and efficient technique for hemostasis Current guidelines suggest the use of Hemospray® as adjunctive to standard treatment New Findings Hemospray® can be used as first-line treatment for bleeding tumors or post-endoscopic interventions TC-325 could provide satisfactory hemostasis as a bridge to definitive therapy in technically difficult cases or in hemodynamic instability Declarations Funding: No funding/grant received for this study Author Contribution AP performed the statistical analysis and wrote the manuscript; RJH was the primary investigator and supervised the study; NA coordinated data collection and study design; MH, DA, SAG, IV, TAH, MFL, JFS, JWR, BH, EJD, AM, SM, PB, JMD, IM, DM, DE, ML, KR, JTA, PB, MG, RK, EC, ERS, TAG, MD, BN, AT, RSL contributed to patients' recruitment, reviewing and editing the manuscript. Conflict of Interest: Rehan J Haidry declares: Pentax Medical, Apollo Endosurgery, Medtronic, Odin Vision, Cook Endoscopy, Fractyl Limited, Endogastric solutions Enrique Rodríguez de Santiago declares: Olympus, Norgine and Apollo Endosurgery (Educational activities) Adacyte therapeuthics (Advisory) The other authors have nothing to declare Seth A Gross declares: Cook, Medtronic, Olympus, Microtech References Kawanami S, Egami Y, Sugae H, Ukita K, Kawamura A, Nakamura H, et al. Predictors of bleeding events in acute decompensated heart failure patients with antithrombotic therapy: AURORA study. ESC Heart Fail. 2023;10(2):1114–21. Moudallel S, van den Eynde C, Malý J, Rydant S, Steurbaut S. Retrospective analysis of gastrointestinal bleedings with direct oral anticoagulants reported to EudraVigilance. Naunyn Schmiedebergs Arch Pharmacol. 2023;396(6):1143–53. Oakland K. Changing epidemiology and etiology of upper and lower gastrointestinal bleeding. 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Chan SM, Lau JYW. Is hemospray the ultimate answer to malignant GI bleeding? Gastrointest Endosc. 2020;91(2):329–31. Chen YI, Barkun AN, Soulellis C, Mayrand S, Ghali P. Use of the endoscopically applied hemostatic powder TC-325 in cancer-related upper GI hemorrhage: preliminary experience (with video). Gastrointest Endosc. 2012;75(6):1278–81. Pittayanon R, Prueksapanich P, Rerknimitr R. The efficacy of Hemospray in patients with upper gastrointestinal bleeding from tumor. Endosc Int Open. 2016;04(09):E933–6. Hussein M, Alzoubaidi D, O’Donnell M, de la Serna A, Bassett P, Varbobitis I, et al. Hemostatic powder TC-325 treatment of malignancy‐related upper gastrointestinal bleeds: International registry outcomes. J Gastroenterol Hepatol. 2021;36(11):3027–32. Pittayanon R, Khongka W, Linlawan S, Thungsuk R, Aumkaew S, Teeratorn N, et al. Hemostatic Powder vs Standard Endoscopic Treatment for Gastrointestinal Tumor Bleeding: A Multicenter Randomized Trial. Gastroenterology. 2023;165(3):762–772.e2. Maluf-Filho F, Martins B da C, de Lima MS, Leonardo DV, Retes FA, Kawaguti FS, et al. Etiology, endoscopic management and mortality of upper gastrointestinal bleeding in patients with cancer. United European Gastroenterol J. 2013;1(1):60–7. Lu SW, Pai CP, Yang TH, Lu JX, Hsiao CH, Yen CC. Clinical characteristics and risk factors for 30-day mortality in esophageal cancer patients with upper gastrointestinal bleeding: a multicenter study. Front Oncol. 2023;13. Shiba M. Risk factors for bleeding after endoscopic mucosal resection. World J Gastroenterol. 2005;11(46):7335. Hussein M, Alzoubaidi D, de la Serna A, Weaver M, Fernandez-Sordo JO, Rey JW, et al. Outcomes of Hemospray therapy in the treatment of intraprocedural upper gastrointestinal bleeding post‐endoscopic therapy. United European Gastroenterol J. 2020;8(10):1155–62. Tables Table 1. Main characteristics of the recruited sample Peptic ulcer disease (n =48 ) Upper GI malignancy (n=79) Post endotherapy (n=37) Lower GI bleeding (n=26) Age, median (IQR), Years 71 (63-78) 69 (58-78) 71 (64-77) 66 (51 – 81) Female, n (%) 20 (41.7) 28 (35.4) 7 (18.9) 11 (42.3) Median Blatchford score 13 10 3 Table 2. Study outcomes stratified per cause of bleeding Peptic ulcer disease (n=48) Upper GI malignancy (n=79) Post endotherapy (n=37) Lower GI bleeding (n=26) Immediate hemostasis 88% (95%CI:75-95) 100% (95%CI:91-100) 100% (95%CI:91-100) 96%(95%CI:80–100) Re-Bleed rate 26% (95%CI:13-43) 17% (95%CI:9-28) 3.1% (95%CI:0-16) 23% (95%CI:8-45) 7-day mortality, n (%) 11% (95%CI:3-25) 7% (95%CI:2-16) 3.1% (95%CI:0-16) 14% (95%CI:3-35) 30-day mortality, n (%) 26% (95%CI:13-43) 25% (95%CI:15-36) 3.1% (95%CI:0-16) 32% (95%CI:14-55) Additional Declarations No competing interests reported. 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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-3923533","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":270807509,"identity":"60569637-8104-49a1-8230-e90c0e3c788c","order_by":0,"name":"Apostolis Papaefthymiou","email":"","orcid":"","institution":"Cleveland Clinic","correspondingAuthor":false,"prefix":"","firstName":"Apostolis","middleName":"","lastName":"Papaefthymiou","suffix":""},{"id":270807510,"identity":"1e35abf9-5487-4d5a-ba73-fbe6248be4b1","order_by":1,"name":"Nasar Aslam","email":"","orcid":"","institution":"University College London Hospitals NHS Foundation Trust","correspondingAuthor":false,"prefix":"","firstName":"Nasar","middleName":"","lastName":"Aslam","suffix":""},{"id":270807511,"identity":"ed0d54d1-5858-4baf-98cd-7886b09a837f","order_by":2,"name":"Mohamed Hussein","email":"","orcid":"","institution":"University College London","correspondingAuthor":false,"prefix":"","firstName":"Mohamed","middleName":"","lastName":"Hussein","suffix":""},{"id":270807512,"identity":"1caa01ad-0de6-46e3-8403-f0b5212cffa3","order_by":3,"name":"Durayd Alzoubaidi","email":"","orcid":"","institution":"University College London","correspondingAuthor":false,"prefix":"","firstName":"Durayd","middleName":"","lastName":"Alzoubaidi","suffix":""},{"id":270807513,"identity":"8737f33d-a0d3-47bf-9981-af8012e9069f","order_by":4,"name":"Seth A Gross","email":"","orcid":"","institution":"NYU Langone","correspondingAuthor":false,"prefix":"","firstName":"Seth","middleName":"A","lastName":"Gross","suffix":""},{"id":270807514,"identity":"5f688f62-3c55-4bdf-8e83-e592ec5e7942","order_by":5,"name":"Alvaro De La Serna","email":"","orcid":"","institution":"Ramon y Cajal University Hospital, IRYCIS, CIBEREHD, University of Alcala","correspondingAuthor":false,"prefix":"","firstName":"Alvaro","middleName":"De La","lastName":"Serna","suffix":""},{"id":270807515,"identity":"58314387-27be-4a1f-b2d6-c5f5ab9dc952","order_by":6,"name":"Ioannis Varbobitis","email":"","orcid":"","institution":"Nottingham University Hospitals","correspondingAuthor":false,"prefix":"","firstName":"Ioannis","middleName":"","lastName":"Varbobitis","suffix":""},{"id":270807516,"identity":"94d9dff3-faa5-4f12-911e-ff0300f34a9c","order_by":7,"name":"Tricia A. 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After Hemospray® application (b,c) hemostasis was achieved (d)\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-3923533/v1/cded6d29fc6261b9e7efd667.png"},{"id":50748707,"identity":"341cf1a0-6bd3-4c3b-9a8e-e4a6142ee507","added_by":"auto","created_at":"2024-02-06 17:17:53","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":86097,"visible":true,"origin":"","legend":"\u003cp\u003eCauses of GI bleeding post-endoscopic intervention\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-3923533/v1/efb4268e9b4a01615f176b39.png"},{"id":50746876,"identity":"6193550f-517a-4f2a-a166-5cb0ac122c61","added_by":"auto","created_at":"2024-02-06 17:09:53","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":139476,"visible":true,"origin":"","legend":"\u003cp\u003eProposed algorithm for Hemospray® use in GI bleeding\u003c/p\u003e","description":"","filename":"Figure5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3923533/v1/578650a870feedfa993b7d8b.jpg"},{"id":50768235,"identity":"a97b4902-6156-4fd7-bf0b-9c5033d3d9a5","added_by":"auto","created_at":"2024-02-07 03:41:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2291181,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3923533/v1/619960f2-dc6e-41da-bdac-07fb0bee0087.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Hemospray® (Hemostatic powder TC-325) as monotherapy for acute gastrointestinal bleeding: a multi-center prospective study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAcute gastrointestinal bleeding (AGIB) is a common medical emergency, especially in the era of the broadly used antithrombotic agents.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Depending on the origin of the bleeding, AGIB is defined as upper GIB (UGIB), when located proximally to the ligament of Treitz, and lower GIB (LGIB) when it occurs elsewhere in the alimentary tract. The frequency of UGIB follows a reducing trend over the last two decades, probably due to the eradication of \u003cem\u003eHelicobacter pylori\u003c/em\u003e and the broad prescription of proton pump inhibitors (PPIs).\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e More specifically, UGIB is recorded at a rate of 67 cases per 100,000 population in the United States of America\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e 134 per 100,000 population in the UK\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e and 47 per 100,000 in Spain.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e Similarly, the incidence of UGIB-related deaths has reduced, as indicated by a database study of peptic ulcer bleeding from the US, conducted between 1989 and 2009, which found that the mortality rate had halved, falling from 4.5 to 2.1%.\u003csup\u003e6\u003c/sup\u003e Although LGIB is more common than UGIB, limited data exist in the literature regarding its prevalence in the general population. Interestingly, the rate of diverticular disease and angiodysplasia-related bleeding has increased, probably reflecting the use of antiplatelets and oral anticoagulants.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eEndoscopic hemostasis represents the mainstay treatment alongside optimisation of medical care. This is supported by studies revealing a reduction in overall mortality caused by GI bleeding. Gastrointestinal Endoscopy Societies have published thorough guidelines on the management of AGIB, favouring dual hemostasis as the optimal approach in cases of active hemorrhage.\u003csup\u003e\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Mechanical treatment, including a variety of endoscopic clips and bands, provides a reliable and lasting effect, especially when applied to focal lesions and vessels. Similarly, thermal ablation techniques target actively bleeding or high-risk spots with equivalent efficacy. Injection with adrenaline solution provides a combined tamponade and vasoconstritive effect, however it is limited by the short duration and needs to be accompanied with another technique.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e These techniques require fine movements to target the bleeding site, which may be challenging in difficult positions or when there is a large abnormal surface, such as malignancies.\u003c/p\u003e \u003cp\u003eCombination therapy, including at least two of the aforementioned modalities is strongly recommended by current guidelines and supported by high quality evidence.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Although the available modalities offer an adequate effect on hemostasis, single treatment with epinephrine injection is inferior to combination therapies with thermal or mechanical hemostasis. At least in cases with active bleeding, epinephrine injection in the bleeding site followed by cauterization or clipping provides lower rates of rebleeding and need for emergency surgery.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e However, in cases with hard and unstable endoscopic position, unavailability of sophisticated devices, such as over-the-scope clips, and inadequate endoscopic experience, combined hemostasis can be impossible.\u003c/p\u003e \u003cp\u003eTopical hemostatic powders offer a treatment modality that is easy to use with a minimal learning curve. Therefore, they provide a promising alternative, especially when a targeted treatment cannot be provided. Additional benefits include the ability to treat a large surface area and their non-contact nature. TC-325 (Hemospray\u0026reg;; Cook Medical, Winston-Salem, North Carolina, USA) is a mineral-based hygroscopic powder that is deployed using a pressurised carbon dioxide cannister. \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e When Hemospray\u0026reg; comes into direct contact with blood it triggers a clotting cascade which results in the formation of a coagulum. This leads to a tamponade effect over the bleeding foci by forming an adhesive seal which results in hemostasis. The powder then sloughs off the mucosa over the proceeding 24\u0026ndash;72 hours.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e Althought these hemostatic agents seem to yield an acceptable rate of bleeding cessation, they are currently recommended as rescue theraphy as opposed to primary theraphy.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe aim of this single-arm, prospective, multi-centre international registry study was to evaluate hemostasis outcomes and adverse events in consecutive patients who received Hemospray\u0026reg; as endoscopic monotherapy for AGIB, in various locations and with different underlying causes.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003eA prospective international multi-center study was conducted, in form of a registry, to investigate the efficacy of Hemospray\u0026reg; on AGIB as monotherapy. The Hemospray\u0026reg; Registry was presented to the local research ethics committee (London-South East Research Ethics Committee) and received ethical approval in October 2016. (ISRCTN29594250). A total of 18 centres across 3 continents (Europe, USA, Australia) have contributed to the registry between January 2016 \u0026ndash; February 2022. The study protocol conformed to the ethical guidelines of the last revision of Declaration of Helsinki and complied with Good Clinical Practice Guidelines.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e Patients' anonymity was ensured and all of recruited subjects provided a written informed consent for their participation in this trial.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eInclusion criteria\u003c/h2\u003e \u003cp\u003eAdult patients with evidence of AGIB were considered as eligible to undergo endoscopic hemostasis with TC-325. UGIB was suspected in patients with melena, hematemesis or Glasgow-Blatchford score\u0026thinsp;\u0026ge;\u0026thinsp;1. Cases with hematochezia and abnormal Oakland score were treated as LGIB, unless evidence of UGIB existed (e.g. increased urea, hemodynamic instability). The final decision for enrollment was at the endoscopists\u0026rsquo; discretion during the endoscopy. Regarding peptic ulcers, only cases with active bleeding in endoscopy were recruited (Forrest Type 1a and Type 1b).\u003c/p\u003e \u003cp\u003ePatients were excluded if they did not consent to participate in the study, had prior failed attempts for hemostasis on the same or previous session, or when TC-325 was used as part of combined hemostasis (adjunctive to clips or thermocautery).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eProcedure\u003c/h2\u003e \u003cp\u003eFollowing rescusitation with intravenous fluids and personalised medical treatment, where needed (e.g. PPIs, red-blood cells transfusion), upper or lower GI endoscopy was offered depending on the suspected area of bleeding.\u003c/p\u003e \u003cp\u003eUpon the identification of the bleeding site, TC-325 was sprayed on the lesion, using the commercially available system (Hemospray\u0026reg;; Cook Medical, Winston-Salem, North Carolina, USA). This system includes a canister filled with the powder, a 7 or 10Fr delivery catheter, and a CO\u003csub\u003e2\u003c/sub\u003e pump incorporated to a handle controlling the propulsion of the powder. After obtaining a clear field in front of the bleeding site, the working channel of the endoscope was dried with air inflation, followed by the catheter insertion at 1-2cm from the bleeding lesion. Short bursts were performed to release the powder under direct vision until the area was completely covered by the powder. The site was then observed for at least five minutes to assess for immediate hemostasis or the need for complementary treatment.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eData collection\u003c/h2\u003e \u003cp\u003eA predefined online platform was used to insert and keep the records of the enrolled cases, including the variables that were analyzed. Only the primary investigators (NA, RJH) had access to the patients\u0026rsquo; records across centers.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eOutcomes and definitions\u003c/h2\u003e \u003cp\u003eGiven the different behaviour and impact of the potential bleeding causes and the challenges raised by the location, the outcomes were measured depending on the cause (e.g. peptic ulcer, malignancy, iatrogenic bleeding) and the bleeding site (upper or lower GI) in order to identify any potential benefit from TC-325 related to these variables.\u003c/p\u003e \u003cp\u003eThe primary endpoint was defined as the rate of immediate endoscopic hemostasis using the Hemospray\u0026reg; device. This was defined as the intraprocedure observation of bleeding cessation within the first 5 minutes post monotherapy with TC-325, without recurrence on the same session. The 5 minutes threshold was also used in previous studies, representing a reasonable comparator.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eRebleeding rates, diagnosed when clinical hemorrhage was observed (new hematemesis or melena associated with hemodynamic change following index treatment) or drop in haemoglobin\u0026thinsp;\u0026gt;\u0026thinsp;2g/L, were considered as a secondary outcome.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e Moreover, 7- and 30-day all cause mortality rates were calculated. As for any interventional procedure, the frequency and the severity of adverse events were also evaluated.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eFollow-up\u003c/h3\u003e\n\u003cp\u003eA 30 days follow up was agreed, either with a face-to-face clinic review or telephone consultation, to assess for recurrence or adverse events.\u003c/p\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eData analysis was performed using the Statistical Package for Social Science Software for Windows (IBM SPSS Statistics, Version 28.0. Armonk, NY: IBM Corp). Continuous variables are presented as mean (\u0026plusmn;\u0026thinsp;standard deviation; SD) and categorical variables are shown as percentages.\u003c/p\u003e \u003cp\u003eWe examined the association between the recorded independent variables and the outcomes. Logistic regression was performed in two stages. Firstly, association between each factor and outcomes was examined separately as a univariable analysis. If several factors showed a statistically significant association with the primary outcomes, we then examined the joint association between the factors as part of a multivariable analysis. Where appropriate we adopted a backwards stepwise selection procedure to omit non-significant variables from the final model.\u003c/p\u003e \u003cp\u003eOdds ratios (OR) and their 95% confidence intervals (CIs) were derived from each variable coefficient in the final model. Statistical significance was considered for P values\u0026thinsp;\u0026le;\u0026thinsp;0.05 (two tailed).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eOne hundred and ninety patients were finally included in our cohort and received TC-325 as monotherapy between January 2016 and February 2022. The age ranged between 51 and 81 years with median being 66\u0026ndash;71 years among subgroups, and the male to female ratio was 2:1. Immediate hemostasis was yielded in 96.3% (95%CI: 92.6\u0026ndash;98.5; 183/190) of patients with an overall recurrence rate of 17.4% (95%CI: 11.9\u0026ndash;24.1; 28/161). Sixteen out of 161 patients [9.9% (95%CI: 5.8\u0026ndash;15.6)] died withing 7 days post-hemostasis with this outcome raised to 21.7% (95%CI: 15.6\u0026ndash;28.9; 35/161) after one month.\u003c/p\u003e \u003cp\u003eFour subgroups were identified, including cases with bleeding peptic ulcer (n\u0026thinsp;=\u0026thinsp;48), upper GI malignancy (n\u0026thinsp;=\u0026thinsp;79), post endoscopic treatment-related hemorrhage (n\u0026thinsp;=\u0026thinsp;37), and lower GI lesions (n\u0026thinsp;=\u0026thinsp;26). \u003cb\u003eTable\u0026nbsp;1\u003c/b\u003e depicts the main information of these subgroups.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003ePeptic ulcer related bleeding\u003c/h2\u003e \u003cp\u003eForty eight patients with Forrest Ia or Ib ulcer were included out of a total 74 cases with ulcer related bleeding \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e The rationale for Hemospray in this seting is that once it comes into contact with blood it forms a cohesive and adhesive barrier that tamponades the bleeding lesion. This subsequently promotes the concentration of clotting factors and cellular elements that may activate the clotting cascade.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e In our cohort, immediate hemostasis was achieved in 42/48 patients equating to a rate of 88% (95%CI:75\u0026ndash;95).\u003cb\u003e(Table\u0026nbsp;2)\u003c/b\u003e The Blatchford score was borderline associated with failed haemostasis; every 5-unit increase in the score resulted in an increasing odd of failure by 5-fold (p\u0026thinsp;=\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe secondary outcomes \u003cb\u003e(Table\u0026nbsp;2)\u003c/b\u003e were assessed in 38 patients who attended follow-up. Rebleeding was observed in 26% (95%CI:13\u0026ndash;43; 10/38) of cases. After the index hemostasis, seven patients died within 7 days [11% (95%CI:3\u0026ndash;25)] and 10 patients within 30 days [26% (95%CI:13\u0026ndash;43; 10/38). Univariate analysis showed an increased ASA score was associated with 30-day mortality. Mortality was 6% in patents with an ASA grade 1\u0026ndash;2 compared to 44% with an ASA grade 4\u0026ndash;5. The odds of death were 12 times higher for patients with higher ASA grades (p\u0026thinsp;=\u0026thinsp;0.03), and the significance was preserved on multivariable analysis [OR: 23.5 (95%CI:1.60\u0026ndash;345); p\u0026thinsp;=\u0026thinsp;0.02].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eUpper GI malignancy\u003c/h2\u003e \u003cp\u003eSeventy-nine patients with an upper GI cancer were recruited in this subgroup (19 esophagus, six esophagogastric junction, 51 gastric, three duodenal). The primary outcome was achieved in 100% (79/79) of upper GI malignancy cases, regardless of the location or lesion size. \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eRebleeding after primary hemostasis was observed in 12 patients [17% (95%CI:9\u0026ndash;28)] among 69 patients who had follow-up information available. The median tumour size was 30mm (IQR: 19\u0026ndash;50) and there was a tendency for rebleeding among lesions\u0026thinsp;\u0026gt;\u0026thinsp;40mm (27% vs 10%), albeit non-significant (p\u0026thinsp;=\u0026thinsp;0.09). The mortality rate after primary hemostasis among those followed-up (N\u0026thinsp;=\u0026thinsp;69) was 7% (95%CI:2\u0026ndash;16; 5/69) within seven days, and 25% (95% CI:15\u0026ndash;36; 17/69) within 30 days. Hemodynamic instability was associated with a 9-fold increased 30-day mortality compared to those with hemodynamic stability [OR:8.89 (95%CI:1.58\u0026ndash;49.9); p\u0026thinsp;=\u0026thinsp;0.01].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003ePost Upper GI endoscopic therapy\u003c/h2\u003e \u003cp\u003ePost-procedure bleeding was diagnosed and treated with TC-325 after various procedures, as presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAn optimal rate of immediate hemostasis was achieved [100% (95%CI:91\u0026ndash;100); 37/37], for all of the different procedures. Only one case of endoscopic mucosal resection (EMR) [3.1% (95%CI:0\u0026ndash;16); 1/32] presented with rebleeding, with the defect been 50mm and the resected lesion 22.5mm. One patient died within the first seven and thirty days [3.1% (95%CI:0\u0026ndash;16); 1/32].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eLower GI bleeding\u003c/h2\u003e \u003cp\u003eA total of 26 patients received Hemospray\u0026reg; for LGIB, and in all but one the primary outcome was achieved [96%(95%CI:80\u0026ndash;100); 25/26]. Follow-up information was available in 22 cases with a rebleeding rate of 23% (95%CI:8\u0026ndash;45; 5/22). The univariable analysis revealed that age and hemodynamic status were significantly associated with rebleeding. More specifically, for every 10-year increase in age the risk of rebleeding was reduced by 5-fold (p\u0026thinsp;=\u0026thinsp;0.03), whereas it was 18 times higher in patients who were hemodynamically unstable when compared to those who were hemodynamically stable (p\u0026thinsp;=\u0026thinsp;0.04). Post-hemostasis, mortality was 14% (95%CI:3\u0026ndash;35; 3/22) within the first seven days and 32% (95% CI: 14\u0026ndash;55%; 7/22) within the first 30 days; none of the factors included in our regression models was linked with 30-day mortality.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eAdverse Events\u003c/h2\u003e \u003cp\u003eA single complication was reported in the registry with the endoscopist reporting catheter blockage during the treatment of a duodenal ulcer. Despite this, immediate hemostasis was achieved and there were no reports of rebleeding.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis prospective multi-center registry assessed the efficacy of Hemospray\u0026reg; as monotherapy. Immediate hemostasis was achieved in 88\u0026ndash;100% across a range of GI bleeding scenarios. The highest rates were recorded in malignancy and post-endoscopic intervention related bleeding, where TC-325 was universally successful. Interestingly, these two subgroups were associated with the lowest rates of recurrent hemorrhage (17% and 3.1%, respectively), whereas one fourth of peptic ulcers and LGI lesions rebled. A recent meta-analysis assessed the pooled rates of 19 studies, including 212 cases where Hemospray\u0026reg; was used as monotherapy. Their outcomes were similar to ours with an immediate hemostasis rate of 91% (95%CI: 79\u0026ndash;96), regardless the combined use with other modalities, the intensity of bleeding, and its cause. The early rebleeding rate was 21% (95%CI; 14\u0026ndash;31), which is higher than the 17.4% (95%CI:11.9\u0026ndash;24.1) observed in our registry across all scenarios.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e Within the first month after hemostasis, the mortality among patients treated for a peptic ulcer or upper GI malignancy was 25%, which was higher among those with an advanced ASA score or haemodynamic instability. Only one patient died post-EMR, whereas the higher mortality rates were detected among patients with LGIB, however none of the evaluated variables was associated with this outcome. Finally, TC-325 monotherapy was an extremely safe treatment with only once adverse event reported secondary to catheter blockage. In 2023, a Field Safety Notice was released regarding adherence of the endoscope to the haemostatic powder while deployed in a retroflexed position, but this was not seen in the registry.\u003c/p\u003e \u003cp\u003eTreating active peptic ulcer-related bleeding requires at least two hemostatic techniques with hemostatic powders, such as TC-325, considered for refractory or recurrent cases.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Hemospray\u0026reg; monotherapy yielded bleeding cessation in 88% (95%CI:75\u0026ndash;95) of cases, however the recurrence rate was considerable [26% (95%CI:13\u0026ndash;43)], accompanied with a similarly high mortality rate within the first month [26% (95%CI:13\u0026ndash;43)]. Interestingly, the increasing ASA score, reflecting the patients\u0026rsquo; comorbidities and perioperative risk, was an independent predictor of mortality with an OR: 23.5. We have previously shown among 202 patients who received Hemospray\u0026reg; monotherapy (25%), combination therapy (75%) or Hemospray\u0026reg; rescue therapy (25%), that the overall rate of hemostasis is 88%, without difference among subgroups. Similarly, there was no difference in rebleeding rates (17%) and early mortality (12%), however the one-month mortality rates were significantly lower when a combined hemostasis approach was applied compared to monotherapy (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003csup\u003e15\u003c/sup\u003e Despite the theoretical risk of failure and rebleeding in cases with spurting hemorrhage (Forrest Ia), it is not homogenously supported by the literature.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e The high rates of immediate hemostasis and the non-inferiority compared to the combined approach for this outcome, reveal a significant role for TC-325 in achieving a direct effect on the active bleeding site, especially when combined hemostasis cannot be achieved, as happens in difficult position, marginally stable patients, or unclear field. Hemospray\u0026reg; could be used in these cases as a bridge therapy, in order to gain time with primary control before a second look endoscopy, especially when resources are limited, or when the patient needs to be transferred to another center for definitive treatment. However, the significantly higher rates of mortality in monotherapy cases with comorbidities imply the need for confirmation of hemostasis with a second endoscopy and complementary treatment where needed. Potential causes associated with these rates need to be assessed by future studies, thereby evaluating the clinical approach policies post-hemospray monotherapy for peptic ulcer, including restarting feeding, transfusion policy and antithrombotics continuation.\u003c/p\u003e \u003cp\u003eMalignancy related bleeding is notoriously difficult to treat given the lack of direct target for endotherapy, the tumour tissue friability, the diffuse bleeding and the absence of a sinlge bleeding vessel.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e The wide field of treatment during the application of Hemospray makes it a helpful endoscopic option for this indication,\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e and we have shown immediate hemostasis is achieved in 100% of the cases. Similar studies provide equivalent results regarding immediate efficacy.\u003csup\u003e\u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e Additionally, TC-325 reduces significantly the required transfusions in this patients group.\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e A recent RCT randomized 106 patients with malignancy GI bleeding to receive monotherapy with Hemospray\u0026reg; or the standard treatment (thermal or mechanical modalities or adrenaline injection alone or in combination). Immediate hemostasis rate was significantly higher using Hemospray\u0026reg; compared to the conventional techniques (100% vs 68.6% respectively; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and, more interestingly, the recurrence rates were lower in the Hemospray\u0026reg; group as well (2.1% vs 21.3%; p\u0026thinsp;=\u0026thinsp;0.003). However, we should note that up to 20% of the standard treatment cohort were managed with ephinephrine therapy alone.\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e In our cohort, rebleeding occurred in 17% of cases with lesions larger than 4cm presenting a non-significant tendency for recurrence, however data on variables affecting this outcome (e.g. morphology, location of the lesion, coagulation status) need to be elucidated by future studies. Considering mortality, a low number of patients (7%) died during the first week, though this rate was increased within a month, especially among patients who presented with hemodynamic instability. This outcome shows heterogeneity in the literature ranging between 18.9\u0026ndash;44.9% within 30-days post bleeding, with active bleeding during the endoscopy increasing the risk of death by 2.24.\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e,\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAnother field, where Hemospray\u0026reg; could represent a reliable choice as monotherapy is post-endoscopic intervention bleeding. In our cohort, the immediate hemostasis was yielded in all of bleeding cases with only one patients presenting with recurrence. This single case occurred following colonic EMR where the lesion was 50mm in size.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e Similar results of optimal hemostasis are also presented by our group in a relative study, with recurrencies occurring in two post-EMR patients out of fifty-seven (4%).\u003csup\u003e29\u003c/sup\u003e Data on the performance of Hemospray\u0026reg; in LGIB is limited, however it appears equivalent to UGIB.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e Although immediate bleeding cessation was achieved in almost all of our patients, the recurrence rate was relatively high [23% (95%CI:8\u0026ndash;45%)], probably reflecting a persistent LGIB etiology in most cases, such as diverticular disease. Finally, TC-325 is already established in terms of safety, with the most common adverse event being the catheter blockage.\u003c/p\u003e \u003cp\u003eThe most significant limitation of this multi-centre prospective registry study is that of its non-randomised design with no comparator. Patient selection for monotherapy use was at the discretion of the endoscopist as opposed to a set criteria/protocol which has potentially introduced an element of selection bias. Furthermore, excluding patients who underwent combination therapy with other endoscopic modalities could influence the true efficacy of Hemospray\u0026reg; monotherapy. This is because initial use with a hemostatic powder may have required salvage intervention during the same procedure. Moreover, detailed aspects regarding macroscopic features of bleeding lesions or histological diagnosis regarding malignancy were not extracted which could have impacted our outcome measures. A significant drawback is the fact that the exact cause of death for patients was not documented, meaning that we cannot directly attribute rebleeding or immediate hemostasis to mortality.\u003c/p\u003e \u003cp\u003eEndoscopic hemostasis using the TC-325 powder as monotherapy is safe and effective, especially in hemorrhage due to malignant lesions or post-endoscopic intervention. \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e In peptic ulcer-related bleeding it could achieve immediate results when the combined standard of care treatment is not feasible. This enables more time to optimise patients\u0026rsquo; condition and make a definite plan. In these cases, a second look endoscopy could be considered to confirm the outcome and intervene when necessary, however this approach should be further evaluated.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eKey Findings\u003c/h2\u003e \u003cp\u003eEstablished knowledge\u003c/p\u003e \u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eTC-325 represents a safe and efficient technique for hemostasis\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCurrent guidelines suggest the use of Hemospray\u0026reg; as adjunctive to standard treatment\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e \u003cp\u003eNew Findings\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eHemospray\u0026reg; can be used as first-line treatment for bleeding tumors or post-endoscopic interventions\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eTC-325 could provide satisfactory hemostasis as a bridge to definitive therapy in technically difficult cases or in hemodynamic instability\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eNo funding/grant received for this study\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAP performed the statistical analysis and wrote the manuscript; RJH was the primary investigator and supervised the study; NA coordinated data collection and study design; MH, DA, SAG, IV, TAH, MFL, JFS, JWR, BH, EJD, AM, SM, PB, JMD, IM, DM, DE, ML, KR, JTA, PB, MG, RK, EC, ERS, TAG, MD, BN, AT, RSL contributed to patients' recruitment, reviewing and editing the manuscript.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConflict of Interest:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRehan J Haidry declares:\u0026nbsp;Pentax Medical, Apollo Endosurgery, Medtronic, Odin Vision, Cook Endoscopy, Fractyl Limited, Endogastric solutions\u003c/p\u003e\n\u003cp\u003eEnrique Rodr\u0026iacute;guez de Santiago declares: Olympus, Norgine and Apollo Endosurgery (Educational activities) Adacyte therapeuthics (Advisory)\u003c/p\u003e\n\u003cp\u003eThe other authors have nothing to declare\u003c/p\u003e\n\u003cp\u003eSeth A Gross declares: Cook, Medtronic, Olympus, Microtech\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKawanami S, Egami Y, Sugae H, Ukita K, Kawamura A, Nakamura H, et al. Predictors of bleeding events in acute decompensated heart failure patients with antithrombotic therapy: AURORA study. ESC Heart Fail. 2023;10(2):1114\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoudallel S, van den Eynde C, Mal\u0026yacute; J, Rydant S, Steurbaut S. Retrospective analysis of gastrointestinal bleedings with direct oral anticoagulants reported to EudraVigilance. Naunyn Schmiedebergs Arch Pharmacol. 2023;396(6):1143\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOakland K. Changing epidemiology and etiology of upper and lower gastrointestinal bleeding. Best Pract Res Clin Gastroenterol. 2019;42\u0026ndash;43:101610.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWuerth BA, Rockey DC. Changing Epidemiology of Upper Gastrointestinal Hemorrhage in the Last Decade: A Nationwide Analysis. 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American Journal of Gastroenterology. 2021;116(5):899\u0026ndash;917.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTriantafyllou K, Gkolfakis P, Gralnek IM, Oakland K, Manes G, Radaelli F, et al. Diagnosis and management of acute lower gastrointestinal bleeding: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2021;53(08):850\u0026ndash;68.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGralnek IM, Stanley AJ, Morris AJ, Camus M, Lau J, Lanas A, et al. Endoscopic diagnosis and management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH): European Society of Gastrointestinal Endoscopy (ESGE) Guideline \u0026ndash; Update 2021. Endoscopy. 2021;53(03):300\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShi K, Shen Z, Zhu G, Meng F, Gu M, Ji F. Systematic review with network meta-analysis: dual therapy for high-risk bleeding peptic ulcers. BMC Gastroenterol. 2017;17(1):55.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBaracat F, Moura E, Bernardo W, Pu LZ, Mendon\u0026ccedil;a E, Moura D, et al. Endoscopic hemostasis for peptic ulcer bleeding: systematic review and meta-analyses of randomized controlled trials. Surg Endosc. 2016;30(6):2155\u0026ndash;68.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJiang SX, Chahal D, Ali-Mohamad N, Kastrup C, Donnellan F. Hemostatic powders for gastrointestinal bleeding: a review of old, new, and emerging agents in a rapidly advancing field. Endosc Int Open. 2022;10(08):E1136\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWorld Medical Association. Declaration of Helsinki, Ethical Principles for Scientific Requirements and Research Protocols. Bull World Health Organ [Internet]. 2013;79(4):373. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/\u003c/span\u003e\u003cspan address=\"https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEuropean Medicines Agency (EMA). Guideline Good Clinical Practice E6(R2). 2018;6(December 2016):1\u0026ndash;68.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHussein M, Alzoubaidi D, Lopez MF, Weaver M, Ortiz-Fernandez-Sordo J, Bassett P, et al. Hemostatic spray powder TC-325 in the primary endoscopic treatment of peptic ulcer-related bleeding: multicenter international registry. Endoscopy. 2021;53(01):36\u0026ndash;43.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLaine L, Spiegel B, Rostom A, Moayyedi P, Kuipers EJ, Bardou M, et al. Methodology for Randomized Trials of Patients With Nonvariceal Upper Gastrointestinal Bleeding: Recommendations From an International Consensus Conference. American Journal of Gastroenterology. 2010;105(3):540\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSung J, Luo D, Wu J, Ching J, Chan F, Lau J, et al. Early clinical experience of the safety and effectiveness of Hemospray in achieving hemostasis in patients with acute peptic ulcer bleeding. Endoscopy. 2011;43(04):291\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMourad FH, Leong RW. Role of hemostatic powders in the management of lower gastrointestinal bleeding: A review. J Gastroenterol Hepatol. 2018;33(8):1445\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOfosu A, Ramai D, John F, Mohan BP, Dhindsa B, Antoine G, et al. The Efficacy and Safety of Hemospray for the Management of Gastrointestinal Bleeding. J Clin Gastroenterol. 2021;55(5):e37\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSung JJY, Moreea S, Dhaliwal H, Moffatt DC, Ragunath K, Ponich T, et al. Use of topical mineral powder as monotherapy for treatment of active peptic ulcer bleeding. Gastrointest Endosc. 2022;96(1):28\u0026ndash;35.e1.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChan SM, Lau JYW. Is hemospray the ultimate answer to malignant GI bleeding? Gastrointest Endosc. 2020;91(2):329\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen YI, Barkun AN, Soulellis C, Mayrand S, Ghali P. Use of the endoscopically applied hemostatic powder TC-325 in cancer-related upper GI hemorrhage: preliminary experience (with video). Gastrointest Endosc. 2012;75(6):1278\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePittayanon R, Prueksapanich P, Rerknimitr R. The efficacy of Hemospray in patients with upper gastrointestinal bleeding from tumor. Endosc Int Open. 2016;04(09):E933\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHussein M, Alzoubaidi D, O\u0026rsquo;Donnell M, de la Serna A, Bassett P, Varbobitis I, et al. Hemostatic powder TC-325 treatment of malignancy‐related upper gastrointestinal bleeds: International registry outcomes. J Gastroenterol Hepatol. 2021;36(11):3027\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePittayanon R, Khongka W, Linlawan S, Thungsuk R, Aumkaew S, Teeratorn N, et al. Hemostatic Powder vs Standard Endoscopic Treatment for Gastrointestinal Tumor Bleeding: A Multicenter Randomized Trial. Gastroenterology. 2023;165(3):762\u0026ndash;772.e2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaluf-Filho F, Martins B da C, de Lima MS, Leonardo DV, Retes FA, Kawaguti FS, et al. Etiology, endoscopic management and mortality of upper gastrointestinal bleeding in patients with cancer. United European Gastroenterol J. 2013;1(1):60\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLu SW, Pai CP, Yang TH, Lu JX, Hsiao CH, Yen CC. Clinical characteristics and risk factors for 30-day mortality in esophageal cancer patients with upper gastrointestinal bleeding: a multicenter study. Front Oncol. 2023;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShiba M. Risk factors for bleeding after endoscopic mucosal resection. World J Gastroenterol. 2005;11(46):7335.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHussein M, Alzoubaidi D, de la Serna A, Weaver M, Fernandez-Sordo JO, Rey JW, et al. Outcomes of Hemospray therapy in the treatment of intraprocedural upper gastrointestinal bleeding post‐endoscopic therapy. United European Gastroenterol J. 2020;8(10):1155\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"409\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"99.51100244498778%\" colspan=\"5\" valign=\"bottom\" style=\"width: 60%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1. Main characteristics of the recruited sample\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.686274509803921%\" style=\"width: 12.2693%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.813725490196077%\" style=\"width: 9.5761%;\"\u003e\n \u003cp\u003ePeptic ulcer disease (n =48 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.794117647058822%\" style=\"width: 13.7656%;\"\u003e\n \u003cp\u003eUpper GI malignancy (n=79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.852941176470587%\" style=\"width: 14.0648%;\"\u003e\n \u003cp\u003ePost endotherapy (n=37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.362745098039216%\" style=\"width: 10.3242%;\"\u003e\n \u003cp\u003eLower GI bleeding (n=26)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.686274509803921%\" style=\"width: 12.2693%;\"\u003e\n \u003cp\u003eAge, median (IQR), Years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.813725490196077%\" style=\"width: 9.5761%;\"\u003e\n \u003cp\u003e71 (63-78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.794117647058822%\" style=\"width: 13.7656%;\"\u003e\n \u003cp\u003e69 (58-78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.852941176470587%\" style=\"width: 14.0648%;\"\u003e\n \u003cp\u003e71 (64-77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.362745098039216%\" style=\"width: 10.3242%;\"\u003e\n \u003cp\u003e66 (51 \u0026ndash; 81)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.686274509803921%\" style=\"width: 12.2693%;\"\u003e\n \u003cp\u003eFemale, \u003cem\u003en\u0026nbsp;\u003c/em\u003e(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.813725490196077%\" style=\"width: 9.5761%;\"\u003e\n \u003cp\u003e20 (41.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.794117647058822%\" style=\"width: 13.7656%;\"\u003e\n \u003cp\u003e28 (35.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.852941176470587%\" style=\"width: 14.0648%;\"\u003e\n \u003cp\u003e7 (18.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.362745098039216%\" style=\"width: 10.3242%;\"\u003e\n \u003cp\u003e11 (42.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.686274509803921%\" style=\"width: 12.2693%;\"\u003e\n \u003cp\u003eMedian Blatchford score \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.813725490196077%\" style=\"width: 9.5761%;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.794117647058822%\" style=\"width: 13.7656%;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.852941176470587%\" style=\"width: 14.0648%;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.362745098039216%\" style=\"width: 10.3242%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"509\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"99.60707269155206%\" colspan=\"5\" valign=\"bottom\" style=\"width: 63.5672%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 2. Study outcomes stratified per cause of bleeding\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.948919449901767%\" style=\"width: 11.4192%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.95088408644401%\" style=\"width: 13.0687%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePeptic ulcer disease (n=48)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.6286836935167%\" style=\"width: 12.8149%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUpper GI malignancy (n=79)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.414538310412574%\" style=\"width: 13.83%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePost endotherapy (n=37)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.664047151277014%\" style=\"width: 12.5612%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLower GI bleeding (n=26)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.948919449901767%\" style=\"width: 11.4192%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eImmediate hemostasis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.95088408644401%\" style=\"width: 13.0687%;\"\u003e\n \u003cp\u003e88% (95%CI:75-95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.6286836935167%\" style=\"width: 12.8149%;\"\u003e\n \u003cp\u003e100% (95%CI:91-100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.414538310412574%\" style=\"width: 13.83%;\"\u003e\n \u003cp\u003e100% (95%CI:91-100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.664047151277014%\" style=\"width: 12.5612%;\"\u003e\n \u003cp\u003e96%(95%CI:80\u0026ndash;100)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.948919449901767%\" style=\"width: 11.4192%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRe-Bleed rate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.95088408644401%\" style=\"width: 13.0687%;\"\u003e\n \u003cp\u003e26% (95%CI:13-43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.6286836935167%\" style=\"width: 12.8149%;\"\u003e\n \u003cp\u003e17% (95%CI:9-28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.414538310412574%\" style=\"width: 13.83%;\"\u003e\n \u003cp\u003e3.1% (95%CI:0-16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.664047151277014%\" style=\"width: 12.5612%;\"\u003e\n \u003cp\u003e23% (95%CI:8-45)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.948919449901767%\" style=\"width: 11.4192%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e7-day mortality, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.95088408644401%\" style=\"width: 13.0687%;\"\u003e\n \u003cp\u003e11% (95%CI:3-25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.6286836935167%\" style=\"width: 12.8149%;\"\u003e\n \u003cp\u003e7% \u0026nbsp;(95%CI:2-16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.414538310412574%\" style=\"width: 13.83%;\"\u003e\n \u003cp\u003e3.1% (95%CI:0-16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.664047151277014%\" style=\"width: 12.5612%;\"\u003e\n \u003cp\u003e14% (95%CI:3-35)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.948919449901767%\" style=\"width: 11.4192%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e30-day mortality, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.95088408644401%\" style=\"width: 13.0687%;\"\u003e\n \u003cp\u003e26% (95%CI:13-43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.6286836935167%\" style=\"width: 12.8149%;\"\u003e\n \u003cp\u003e25% (95%CI:15-36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.414538310412574%\" style=\"width: 13.83%;\"\u003e\n \u003cp\u003e3.1% (95%CI:0-16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.664047151277014%\" style=\"width: 12.5612%;\"\u003e\n \u003cp\u003e32% (95%CI:14-55)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Hemospray®, TC-325, Endoscopy, Upper Gastro-intestinal bleeding, Hemospray monotherapy","lastPublishedDoi":"10.21203/rs.3.rs-3923533/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3923533/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003e Topical hemostatic powders are a reliable second-line approach in acute gastrointestinal (GI) bleeding (AGIB) treatment, according to the existing guidelines. Increasing evidence supports the use of hemostatic powder TC-325 (Hemospray\u0026reg;) as monotherapy in specific GI bleeding scenarios. This prospective, multi-center study evaluated the performance of TC-325 as monotherapy for GI hemorrhage.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eEighteen centres across Europe, and USA contributed between 2016 and 2022 to an international multicentre prospective registry. Adults with AGIB were eligible (melena, hematemesis, hematochezia, Glasgow-Blatchford score\u0026thinsp;\u0026ge;\u0026thinsp;1 or abnormal Oakland score), unless TC-325 was part of combined hemostasis (adjunctive to clips or thermocautery). The primary endpoint was immediate haemostasis. Secondary outcomes were rebleeding, 7- and 30-day mortality rates. Potential associations with risk factors were investigated with statistical significance set for p\u0026thinsp;\u0026le;\u0026thinsp;0.05.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOne hundred and ninety patients were included (age range\u0026thinsp;=\u0026thinsp;51\u0026ndash;81, male:female\u0026thinsp;=\u0026thinsp;2:1). Peptic ulcer (n\u0026thinsp;=\u0026thinsp;48), upper GI malignancy (n\u0026thinsp;=\u0026thinsp;79), post endoscopic treatment-related hemorrhage (n\u0026thinsp;=\u0026thinsp;37), and lower GI lesions (n\u0026thinsp;=\u0026thinsp;26) were diagnosed. The primary outcome was recorded in 96.3% (95%CI:92.6\u0026ndash;98.5) with rebleeding in 17.4% (95%CI:11.9\u0026ndash;24.1) when TC-325 was used as primary monotherapy. Post-hemostasis, 9.9% (95%CI:5.8\u0026ndash;15.6) died within 7 days and 21.7% (95%CI:15.6\u0026ndash;28.9) within 30 days. Regarding peptic ulcer, the immediate hemostasis was achieved in 88% (95%CI:75\u0026ndash;95) and 26% (95%CI:13\u0026ndash;43) rebled. Increased American Society of Anaesthesiologists (ASA) score was associated with mortality [OR:23.5 (95%CI:1.60\u0026ndash;345); p\u0026thinsp;=\u0026thinsp;0.02]. The primary outcome was achieved in 100% of cases with malignancy and post GI intervention bleeding, with rebleeding in 17% and 3.1%, respectively. Twenty-six patients received Hemospray\u0026reg; for lower GI bleeding, and in all but one the primary outcome was achieved.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eTC-325 powder as monotherapy represents a safe and effective modality especially in malignancy- or post-endoscopic intervention-related bleeding. In peptic ulcer bleeding it could be helpful when the standard of care treatment is not feasible or unavailable, to stabilise patients.\u003c/p\u003e","manuscriptTitle":"Hemospray® (Hemostatic powder TC-325) as monotherapy for acute gastrointestinal bleeding: a multi-center prospective study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-06 17:09:48","doi":"10.21203/rs.3.rs-3923533/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"20b23891-c46a-4eba-a8c6-e83e8aeba11c","owner":[],"postedDate":"February 6th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-02-07T03:33:53+00:00","versionOfRecord":[],"versionCreatedAt":"2024-02-06 17:09:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3923533","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3923533","identity":"rs-3923533","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}