Randomised, placebo-controlled trial and meta-analysis show benefit of ondansetron for irritable bowel syndrome with diarrhoea : the TRITON trial
Author
Gunn, DavidTopan, Rabia
Barnard, Lorna
Fried, Ron
Holloway, Ivana
Brindle, Richard
Corsetti, Maura
Scott, Mark
Farmer, Adam
Kapur, Kapil
Sanders, David
Eugenicos, Maria
Trudgill, Nigel
Whorwell, Peter
Mclaughlin, John
Akbar, Ayesha
Houghton, Lesley
Dinning, Phil G
Aziz, Qasim
Ford, Alexander C
Farrin, Amanda J
Spiller, Robin
Affiliation
University of Nottingham; Nottingham University Hospitals NHS Trust; Barts and The London School of Medicine and Dentistry; Sandwell and West Birmingham NHS Trust; et al.Publication date
2023-03-03Subject
Gastroenterology
Metadata
Show full item recordAbstract
Background: Ondansetron may be beneficial in irritable bowel syndrome with diarrhoea (IBS-D). Aim: To conduct a 12-week parallel group, randomised, double-blind, placebo-controlled trial of ondansetron 4 mg o.d. (titrated up to 8 mg t.d.s.) in 400 IBS-D patients. Primary endpoint: % responders using the Food and Drug Administration (FDA) composite endpoint. Secondary and mechanistic endpoints 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: Eighty patients were randomised. On intention-to-treat analysis, 15/37 (40.5%; 95% CI 24.7%-56.4%) met the primary endpoint on ondansetron versus 12/43 (27.9%; 95% CI 14.5%-41.3%) on placebo (p = 0.19). Ondansetron improved stool consistency compared 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, versus placebo -2.2 (10.3) hours, p = 0.01). Meta-analysis of 327 patients from this, and two similar trials, demonstrated ondansetron was superior to placebo for the FDA composite endpoint (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 endpoint 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. Trial registration - http://www.isrctn.com/ISRCTN17508514.Citation
Gunn D, Topan R, Barnard L, Fried R, Holloway I, Brindle R, Corsetti M, Scott M, Farmer A, Kapur K, Sanders D, Eugenicos M, Trudgill N, Whorwell P, Mclaughlin J, Akbar A, Houghton L, Dinning PG, Aziz Q, Ford AC, Farrin AJ, Spiller R. Randomised, placebo-controlled trial and meta-analysis show benefit of ondansetron for irritable bowel syndrome with diarrhoea: The TRITON trial. Aliment Pharmacol Ther. 2023 Jun;57(11):1258-1271. doi: 10.1111/apt.17426Type
ArticlePMID
36866724Publisher
Wileyae974a485f413a2113503eed53cd6c53
10.1111/apt.17426