@article { , title = {Randomised, placebo-controlled trial and meta-analysis show benefit of ondansetron for irritable bowel syndrome with diarrhoea: The TRITON trial}, abstract = {Summary: 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}, doi = {10.1111/apt.17426}, eissn = {1365-2036}, issn = {0269-2813}, issue = {11}, journal = {Alimentary Pharmacology and Therapeutics}, note = {Article not yet published online. On temp embargo sheet. Will need to change status to published. Will need to add official url, volume, issue, pagination and doi. Will need to set 12 month embargo on publication. Will need to add set statement "This is the peer reviewed version of the following article: [FULL CITE], which has been published in final form at [Link to final article using the DOI]. The article must be linked to Wiley’s version of record on Wiley Online Library" KJB 17.2.23 Published with CC BY licence 06/03/2023}, pages = {1258-1271}, publicationstatus = {Published}, publisher = {Wiley}, url = {https://nottingham-repository.worktribe.com/output/17082601}, volume = {57}, keyword = {Pharmacology (medical), Gastroenterology, Hepatology}, year = {2023}, author = {Gunn, David and Topan, Rabia and Barnard, Lorna and Fried, Ron and Holloway, Ivana and Brindle, Richard and Corsetti, Maura and Scott, Mark and Farmer, Adam and Kapur, Kapil and Sanders, David and Eugenicos, Maria and Trudgill, Nigel and Whorwell, Peter and Mclaughlin, John and Akbar, Ayesha and Houghton, Lesley and Dinning, Phil G. and Aziz, Qasim and Ford, Alexander C. and Farrin, Amanda J. and Spiller, Robin} }