Prophylactic clip closure after endoscopic submucosal dissection of large flat and sessile colorectal polyps: a multicentre randomised controlled trial (EPOC trial)

Background Prophylactic clip closure after endoscopic mucosal resection reduces delayed bleeding in large and proximal colon lesions; however, evidence regarding its effectiveness in colorectal endoscopic submucosal dissection (ESD) is lacking. Objective To compare clinically significant delayed bleeding rates between a clip closure and a control group for flat and sessile 20–50 mm colorectal polyps following ESD. Design A multicentre randomised controlled trial conducted at four Japanese institutions randomly assigned patients to closure or non-closure groups. Significant postprocedural bleeding (haematochezia) was classified as severe (requiring endoscopic haemostasis or blood transfusion in patients with haemoglobin levels <70 g/L or haemorrhagic shock) or mild. Results The closure and control groups comprised 150 and 149 cases in the intention-to-treat (ITT) analysis and 142 and 141 cases in the per-protocol (PP) analysis, respectively. Rates of complete clip closure were 88.7% (ITT) and 93.0% (PP). The ITT analysis revealed delayed bleeding rates of 6.7% and 20.1% (OR: 0.28; 95% CI: 0.13 to 0.60; p<0.001; absolute risk difference (ARD): 13.5%; 95% CI: 5.6% to 20.9%) and severe delayed bleeding rates of 1.3% and 8.7% (OR: 0.14; 95% CI: 0.03 to 0.64; p=0.003; ARD: 7.4%; 95% CI: 2.2% to 12.4%) in the closure and control groups, respectively. These differences were confirmed in the PP analysis. Delayed perforation was not observed, and the post-ESD coagulation syndrome rate was not significantly different between the two groups. Multivariate logistic regression analyses identified prophylactic clip closure as a significant independent preventive factor for both delayed bleeding (OR: 0.22; 95% CI: 0.08 to 0.50; p<0.001) and severe delayed bleeding (OR: 0.22; 95% CI: 0.05 to 0.76; p=0.015). Conclusions Prophylactic clip closure, successfully achieved in approximately 90% of cases, reduced the delayed bleeding rate after resection of colorectal polyps measuring 20–50 mm. Trial registration number UMIN000043675.