Efficacy of ramosetron in the treatment of male patients with irritable bowel syndrome with diarrhea: a multicenter, randomized clinical trial, compared with mebeverine

Abstract

Background The 5-HT 3 receptor antagonists are known to be effective for the treatment of diarrheapredominant irritable bowel syndrome (IBS), but not widely used yet. The aim of this study was to compare the efficacy and safety of ramosetron, a 5-HT 3 receptor antagonist, and mebeverine in male patients with IBS with diarrhea (IBS-D). Methods This study was performed in a multicenter, randomized, open-label design. Data of 343 male patients with IBS-D who were randomized to either a 4-week treatment of ramosetron 5 lg once daily or a 4-week treatment of mebeverine 135 mg three times daily were analyzed by the intent-to-treat analysis. The primary efficacy parameter was the proportion of patients with adequate relief of IBS symptoms at the last week of treatment. The secondary endpoints were changes in each symptom score and the safety profiles. Key Results The responder rates for global IBS symptoms, abdominal pain/discomfort and abnormal bowel habits in the ramosetron and mebeverine groups significantly increased during the treatment period. The severity scores of abdominal pain/discomfort and urgency, the stool form score, and the stool frequency in both treatment arms were significantly reduced, compared with the baselines. There were no significant differences in the responder rates (37% vs 38% on ITT analysis) and adverse event profiles between the ramosetron and mebeverine groups. Neither severe constipation nor ischemic colitis was reported by ramosetron-treated patients. Conclusions & Inferences Ramosetron 5 lg once daily is as effective as mebeverine three times daily in male patients with IBS-D.

Efficacy and Safety of 5-Hydroxytryptamine 3 Receptor Antagonists in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…The 21 RCTs involved 10,898 patients with IBS defined according to the Rome criteria: six investigated ramosetron [9,[20][21][22][23][24], 10 assessed alosetron [25][26][27][28][29][30][31][32][33][34], and two compared ondansetron [12,35] with placebo or mebeverine; these studies all scored !4 on the Jadad scale. However, the three cilansetron studies had Jadad scores of 3 [36-38].…”

“…[28] (n = 714, Jadad score = 4) and Lee et al [22] (n = 343, Jadad score = 3) markedly affected heterogeneity. In the former, stool consistency was defined as a GI symptom and the endpoint definition used a "Yes/No" response, while other studies used the US FDA definition [28].…”

“…In the former, stool consistency was defined as a GI symptom and the endpoint definition used a "Yes/No" response, while other studies used the US FDA definition [28]. Lee et al indicated that both ramosetron and mebeverine were effective for improving abnormal bowel habits or stool consistency, but this was not statistically significant [22]. Removing the two studies significantly decreased heterogeneity; I 2 decreased to 38%.…”

“…Fourteen RCTs evaluated the rate of adverse effects: five were on ramosetron [9,[21][22][23][24] and nine were on alosetron [25-32, 34], and involved 7887 patients in total. Heterogeneity was statistically significant (I 2 = 54%; 95% CI: 14.96, 74.67, P = 0.009, Fig 5).…”

“…We found consistent treatment response across studies from different countries; for "relief of global IBS symptoms", "relief of abdominal pain and discomfort" and "relief of abnormal bowel habits or stool consistency", the estimated pooled RR was 1.56 (95% CI: 1.43, 1.71), 1.33 (95% CI: 1.26, 1.39), and 1.63 (95% CI: 1.33, 1.99), respectively. For the endpoint "relief of global IBS symptoms", the six ramosetron studies had statistically significant heterogeneity [9,[20][21][22][23][24]: five analyzed the effect of ramosetron compared with placebo, indicating that ramosetron improves global IBS symptoms [9,20,21,23,24]. Only one study used mebeverine as compared with ramosetron and indicated that both ramosetron and mebeverine were effective, but the treatment groups did not differ statistically significantly from the control groups [22].…”