Effect of ramosetron on stool consistency in male patients with irritable bowel syndrome with diarrhea

Clin Gastroenterol Hepatol. 2014 Jun;12(6):953-9.e4. doi: 10.1016/j.cgh.2013.11.024. Epub 2013 Dec 4.

Abstract

Background & aims: Ramosetron, a serotonin (5-hydroxytryptamine)-3 receptor antagonist with high selectivity, reduced stress-induced diarrhea and defecation caused by corticotropin-releasing hormone in rats. However, there have been no clinical trials of its effect in patients with diarrhea and irritable bowel syndrome (IBS-D). We performed a randomized, double-blind, placebo-controlled trial to determine whether ramosetron reduces diarrhea in these patients.

Methods: Our study included 296 male outpatients with IBS-D treated at 52 centers in Japan. Patients were given 5 μg oral ramosetron (n = 147) or placebo (n = 149) once daily for 12 weeks after a 1-week baseline period. The primary end point was increased stool consistency in the first month. Secondary end points included relief of overall IBS symptoms and increased IBS-related quality of life.

Results: More patients given ramosetron (74, 50.3%) than those given placebo (29, 19.6%) reported improved stool consistency in the first month (P < .001). The relative risk and number needed to treat were 2.57 (95% confidence interval, 1.79-3.70) and 3.25 (95% confidence interval, 2.44-4.89), respectively. The ramosetron group had significantly higher monthly rates of relief of overall IBS symptoms and IBS-related quality of life than the placebo group.

Conclusions: Ramosetron (5 μg oral, once daily for 12 weeks) improved stool consistency in male patients with IBS-D, compared with placebo. These study results, along with the pharmacologic profile of ramosetron, indicate that increased stool consistency is the best end point for studies of ramosetron in patients with IBS-D. Clinicaltrials.gov No, NCT01225237.

Keywords: 5-Hydroxytryptamine (5-HT); Abdominal Discomfort; Abdominal Pain; Global Improvement.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Animals
  • Benzimidazoles / therapeutic use*
  • Chemical Phenomena*
  • Diarrhea / drug therapy*
  • Double-Blind Method
  • Feces*
  • Gastrointestinal Agents / therapeutic use*
  • Humans
  • Irritable Bowel Syndrome / complications*
  • Irritable Bowel Syndrome / drug therapy*
  • Japan
  • Male
  • Middle Aged
  • Placebos / administration & dosage
  • Rats
  • Treatment Outcome
  • Young Adult

Substances

  • Benzimidazoles
  • Gastrointestinal Agents
  • Placebos
  • ramosetron

Associated data

  • ClinicalTrials.gov/NCT01225237