Journal Article

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of High-Dose Rebamipide Treatment for Low-Dose Aspirin-Induced Moderate-to-Severe Small Intestinal Damage

Sakata, Yasuhisa, Fujimoto, Kazuma, Takeuchi, Toshihisa, Naito, Yuji, Yoshikawa, Toshikazu, Shiba, Masatsugu, Handa, Osamu, Higuchi, Kazuhide, Tanigawa, Tetsuya, Arakawa, Tetsuo, Watanabe, Toshio

2015

Overview

Low-dose aspirin (LDA) frequently causes small bowel injury. While some drugs have been reported to be effective in treating LDA-induced small intestinal damage, most studies did not exclude patients with mild damage thought to be clinically insignificant. We conducted a multicenter, randomized, double-blind, placebo-controlled trial to assess the efficacy of a high dose of rebamipide, a gastroprotective drug, for LDA-induced moderate-to-severe enteropathy. We enrolled patients who received 100 mg of enteric-coated aspirin daily for more than 3 months and were found to have more than 3 mucosal breaks (i.e., erosions or ulcers) in the small intestine by capsule endoscopy. Eligible patients were assigned to receive either rebamipide 300 mg (triple dose) 3 times daily or placebo for 8 weeks in a 2:1 ratio. Capsule endoscopy was then repeated. The primary endpoint was the change in the number of mucosal breaks from baseline to 8 weeks. Secondary endpoints included the complete healing of mucosal breaks at 8 weeks and the change in Lewis score (an endoscopic score assessing damage severity) from baseline to 8 weeks. The study was completed by 38 patients (rebamipide group: n = 25, placebo group: n = 13). After 8 weeks of treatment, rebamipide, but not placebo, significantly decreased the number of mucosal breaks (p = 0.046). While the difference was not significant (p = 0.13), the rate of complete mucosal break healing in the rebamipide group (32%, 8 of 25) tended to be higher than that in the placebo group (7.7%, 1 of 13). Rebamipide treatment significantly improved intestinal damage severity as assessed by the Lewis score (p = 0.02), whereas placebo did not. The triple dose of rebamipide was well tolerated. High-dose rebamipide is effective for the treatment of LDA-induced moderate-to-severe enteropathy. UMIN Clinical Trials Registry UMIN000003463.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Aged / Alanine - analogs & derivatives / Alanine - therapeutic use / Anti-Ulcer Agents - therapeutic use / Aspirin / Aspirin - adverse effects / Capsule Endoscopy / Clinical trials / Damage assessment / Dosage and administration / Dose-Response Relationship, Drug / Double-Blind Method / Double-blind studies / Drug Administration Schedule / Drug dosages / Drugs / Endoscopy / Ethics / Female / Gastroenterology / Healing / Hepatology / Hospitals / Humans / Internal medicine / Intestinal Diseases - chemically induced / Intestinal Diseases - diagnosis / Intestinal Diseases - drug therapy / Intestine, Small - drug effects / Intestine, Small - pathology / Male / Medical research / Medicine / Microbiota / Mucosa / Nonsteroidal anti-inflammatory drugs / Patients / Quinolones - therapeutic use / Randomization / Rodents / Severity of Illness Index / Small intestine / Studies / Treatment Outcome / Ulcers / University graduates