Tranexamic Acid Versus Epinephrine as Submucosal Injectate During Endoscopic Mucosal Resection of Large Colorectal Lesions: A Randomized Controlled Trial

Background and Aims: Bleeding and post-procedural pain are common adverse events after endoscopic mucosal resection (EMR) of large colorectal lesions. Epinephrine is frequently added to submucosal injectates, although its benefit for delayed bleeding is inconsistent and associated with post-procedural pain. Tranexamic acid (TXA), an antifibrinolytic agent used to prevent bleeding in several medical conditions, has not been evaluated during colorectal EMR. We compared TXA with epinephrine for bleeding outcomes, safety, and post-procedural pain. Methods: In this prospective, double-blind, randomized controlled pilot trial, adults undergoing EMR for colorectal lesions ≥20 mm were randomized 1:1 to receive a TXA-containing or epinephrine-containing submucosal injectate. Primary outcomes were intraprocedural bleeding severity and delayed bleeding. Secondary outcomes included post-procedural pain, post-polypectomy syndrome, and thromboembolic events. Results: The study included 121 patients (TXA, n = 60; epinephrine, n = 61). Intraprocedural bleeding rates and severity were similar between groups, and hemostasis was achieved endoscopically in all cases. Delayed bleeding occurred in 8.3% of patients in the TXA group and 11.5% in the epinephrine group (p = 0.762); clinically significant delayed bleeding occurred in 6.7% and 6.6%, respectively. Lesion size was the only independent predictor of delayed bleeding. Post-procedural pain was significantly less frequent with TXA (5.0% vs. 39.3%; p < 0.001), and no TXA-treated patients required opioid analgesia compared with 18% in the epinephrine group (p < 0.001). No major adverse events were observed in the TXA group. Conclusions: In this pilot study, TXA achieved bleeding outcomes comparable to epinephrine while significantly reducing post-procedural pain in large colorectal EMR procedures, warranting further evaluation in larger trials.