Colon to Rectum
Aliment Pharmacol Ther. 2023;57(11):1258−71
Randomized, placebo-controlled trial and meta-analysis show benefit of ondansetron for irritable bowel syndrome with diarrhea: The TRITON trial
Background: Ondansetron may be beneficial in irritable bowel syndrome with diarrhea (IBS-D).
Aim: To conduct a 12-week parallel group, randomized, double-blind, placebo-controlled trial of ondansetron 4 mg once daily (titrated up to 8 mg t.d.s.) in 400 IBS-D patients. Primary end point: % responders using the Food and Drug Administration (FDA) composite end point. Secondary and mechanistic end points included stool consistency (Bristol Stool Form Scale) and whole gut transit time (WGTT). After literature review, results were pooled with other placebo-controlled trials in a meta-analysis to estimate relative risks (RR), 95% confidence intervals (CIs) and number needed to treat (NNT).
Results: 80 patients were randomized. On intention-to-treat analysis, 15 of 37 patients (40.5%; 95% CI: 24.7−56.4%) met the primary end point on ondansetron versus 12 of 43 patients (27.9%; 95% CI: 14.5−41.3%) on placebo (p = 0.19). Ondansetron improved stool consistency com-pared with placebo (adjusted mean difference, -0.7; 95% CI: -1.0 to -0.3; p < 0.001). Ondansetron increased WGTT between baseline and week 12 (mean [SD] difference, 3.8 [9.1] hours, vs. placebo -2.2 [10.3] hours; p = 0.01). Meta-analysis of 327 patients from this, and 2 similar trials, demonstrated ondansetron was superior to placebo for the FDA composite end point (RR of symptoms not responding = 0.86; 95% CI: 0.75−0.98, NNT = 9) and stool response (RR = 0.65; 95% CI: 0.52−0.82, NNT = 5), but not abdominal pain response (RR = 0.95; 95% CI: 0.74−1.20).
Conclusions: Although small numbers meant the primary end point was not met in this trial, when pooled with other similar trials meta-analysis suggests ondansetron improves stool consistency and reduces days with loose stool and urgency.
DOI: 10.1111/apt.17426