Accepted for/Published in: JMIR Research Protocols
Date Submitted: Feb 18, 2026
Date Accepted: Aug 31, 2026
Warning: This is an author submission that is not peer-reviewed or edited. Preprints - unless they show as "accepted" - should not be relied on to guide clinical practice or health-related behavior and should not be reported in news media as established information.
Prevention of rebleeding in colonic diverticular bleeding using orengedokuto: study protocol for a double-blind randomized controlled trial (CROCODIVE)
ABSTRACT
Background:
Endoscopic hemostasis is used to treat colonic diverticular bleeding; however, rebleeding is frequently observed after conservative treatment. Currently, evidence regarding the efficacy of oral medications in preventing rebleeding from colonic diverticula is limited. Orengedokuto (Huanglian Jiedu Tang) is a traditional Kampo formula with capillary-constricting and hemostatic properties that is 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 healthcare systems.
Objective:
The aim of this study is to exploratorily evaluate the efficacy and safety of orengedokuto in preventing rebleeding in patients with colonic diverticular bleeding who achieved spontaneous hemostasis, in whom the bleeding source could not be identified endoscopically and therefore endoscopic hemostasis could not be performed.
Methods:
We designed a double-blind, randomized controlled trial to evaluate the efficacy and safety of orengedokuto in patients with colonic diverticular bleeding who achieved spontaneous hemostasis and in whom the bleeding source could not be identified, rendering 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 h 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. The primary endpoint is the proportion of patients who experience rebleeding. Secondary endpoints include the length of hospital stay, time to resumption of oral intake, severity of rebleeding (timing and degree of anemia), and incidence of secondary rebleeding. Safety will be assessed through adverse event monitoring for causality and frequency.
Results:
Enrollment is scheduled from July 2025 to December 2027. 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 healthcare resource use. Clinical Trial: The trial was registered in the Japan Registry for Clinical Trials (jRCTs051250063) on July 8, 2025.
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