title: A multicenter, randomized, double-blind, placebo-controlled trial of high-dose rebamipide treatment for low-dose aspirin-induced moderate-to-severe small intestinal damage.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  High-dose rebamipide is effective for the treatment of LDA-induced moderate-to-severe enteropathy.
  
  
  BACKGROUND
  UMIN Clinical Trials Registry UMIN000003463.
authors: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors: Toshio
authors: T
authors: Watanabe
authors: Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan.
authors: Toshihisa
authors: T
authors: Takeuchi
authors: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Osamu
authors: O
authors: Handa
authors: Department of Internal Medicine and Gastroenterology, Saga Medical School, Saga, Japan.
authors: Yasuhisa
authors: Y
authors: Sakata
authors: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors: Tetsuya
authors: T
authors: Tanigawa
authors: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors: Masatsugu
authors: M
authors: Shiba
authors: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Yuji
authors: Y
authors: Naito
authors: Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan.
authors: Kazuhide
authors: K
authors: Higuchi
authors: Department of Internal Medicine and Gastroenterology, Saga Medical School, Saga, Japan.
authors: Kazuma
authors: K
authors: Fujimoto
authors: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Toshikazu
authors: T
authors: Yoshikawa
authors: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors: Tetsuo
authors: T
authors: Arakawa
mesh_terms: D000368:Aged; D000409:Alanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000897:Anti-Ulcer Agents / Q000627:therapeutic use; D001241:Aspirin / Q000009:adverse effects*; D053704:Capsule Endoscopy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007410:Intestinal Diseases / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy*; D007421:Intestine, Small / Q000187:drug effects* / Q000473:pathology; D008297:Male; D015363:Quinolones / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000897:Anti-Ulcer Agents; D015363:Quinolones; C052785:rebamipide; D000409:Alanine; D001241:Aspirin