Prevention of Rebleeding in Colonic Diverticular Bleeding Using Orengedokuto: Protocol for a Double-Blind Randomized Controlled Trial.

Background: Endoscopic hemostasis is used to treat colonic diverticular bleeding (CDB); however, rebleeding is frequently observed after conservative treatment. Currently, evidence regarding the efficacy of oral medications for preventing rebleeding from colonic diverticula is limited. Orengedokuto (Huanglian Jiedu Tang) is a traditional Kampo formula with capillary-constricting and hemostatic properties that are used to treat bleeding conditions such as epistaxis, hematemesis, and melena. If proven to be effective in preventing rebleeding, orengedokuto could reduce the need for hospitalization and repeat endoscopic procedures, thereby lowering the burden on patients and health care systems. Objective: This study aims to exploratorily evaluate the efficacy and safety of orengedokuto in preventing rebleeding in patients with CDB who have achieved spontaneous hemostasis. Methods: We designed a double-blind, randomized controlled trial in patients with CDB who achieved spontaneous hemostasis and in whom the bleeding source could not be identified, making endoscopic hemostasis unfeasible. Patient allocation will be determined using a dynamic randomization method based on minimization, with a 1:1 assignment ratio. Treatment will begin within 24 hours of enrollment. The participants will receive either orengedokuto plus standard treatment or placebo plus standard treatment for 14 days, followed by a 31-day observation period. They will take 2 capsules of either orengedokuto or placebo 3 times a day. Standard treatment refers to the standard approach for managing CDB, which involves resting the bowel through fasting and intravenous fluid administration. Corn starch will be used for the placebo. The primary end point is the proportion of patients who experience rebleeding. Secondary end points include the length of hospital stay, time to resumption of oral intake, severity of rebleeding (including the timing of rebleeding and degree of anemia), and incidence of secondary rebleeding. Safety will be assessed through monitoring of adverse events for causality and frequency. For the primary end point, the full analysis set will be used as the analysis population. The proportion of patients with rebleeding will be calculated for each group, and intergroup comparisons will be performed. For the secondary end points, statistical comparisons will be performed between the 2 groups. Results: This study received funding from the Japan Agency for Medical Research and Development in May 2025. Enrollment is scheduled from July 2025 to December 2027. As of June 2026, we have enrolled 48 participants. All follow-up and data collection activities will be finalized by February 2028. Results are anticipated to be completed in the first quarter of 2028. Conclusions: If orengedokuto demonstrates a hemostatic effect, it could offer a less invasive alternative to endoscopic hemostasis, potentially reducing hospital stays and overall health care resource use.