Investigation of prophylactic clip haemorrhage control for colorectal cold snare polypectomy in patients taking antithrombotic drugs (PERCOLD): study protocol-a multicentre prospective parallel-group non-inferiority RCT phase 3 trial.

introductionThe effect of prophylactic clipping for colorectal cold snare polypectomy (CSP) on delayed bleeding (DB) in patients with antithrombotic drugs remains unverified. The aim of the PERCOLD study is to demonstrate the non-inferiority of DB rates in cases without prophylactic clips compared with cases with prophylactic clips in patients taking antithrombotic drugs for colorectal CSP through randomised controlled trial (RCT). METHODS AND ANALYSIS: This study is a multicentre prospective parallel-group RCT phase 3 trial that is being conducted at 14 institutions in Japan at the time of writing this manuscript. After providing consent, patients will undergo screening and assessment for study enrolment eligibility. Patients taking antithrombotic drugs (aged 20 years or older at the time of consent and who have agreed to participate in this study) will be selected if they have a preoperative suspected adenoma (including sessile serrated lesion) with an endoscopic diameter of <10 mm and an indication for CSP, provided they do not meet the exclusion criteria. The primary endpoint is the percentage of DB within 2 weeks after CSP per patient. DB is defined as haematochezia requiring endoscopic haemostasis. Secondary endpoints are rate of haematochesia within 2 weeks after CSP (per patient), rate of DB within 2 weeks after CSP (per polyp), percentage of performing endoscopy for haematochesia within 2 weeks after CSP (by patient and polyp), treatment time (from magnification of the first polyp to clip closure of the last polyp in the clip closure group and to observation after last polyp resection in the non-clip closure group) and complication rates (immediate bleeding, intraoperative perforation, delayed perforation and post polypectomy syndrome). The selected patients will be randomised 1:1 into the clip closure group and the non-clip closure group after registration, with 287 patients in each group. ETHICS AND DISSEMINATION: The trial protocol has been approved by the Chiba University Certified Clinical Research Reviewer Board (CRB3180015), which serves as the central ethics committee, and registered with Japan Registry of Clinical Trials. The current protocol V.1.7, dated 4 October 2024. Written informed consent for participation in the study will be obtained from all participating patients. All participating institutions have formally agreed to conduct the study in accordance with this central approval, and local site permissions were obtained as required by each institution. The results of this study will be submitted for publication in international peer-reviewed journals and the key findings will be presented at international scientific conferences. TRIAL REGISTRATION NUMBER: Japan Registry of Clinical Trials (jRCT1032230086).