Aliment Pharmacol Ther. 2023 Mar 3. doi: 10.1111/apt.17426. Online ahead of print.

David Gunn ^1 2, Rabia Topan ^3 4, Lorna Barnard ⁵, Ron Fried ³, Ivana Holloway ⁵, Richard Brindle ⁵, Maura Corsetti ², Mark Scott ³, Adam Farmer ⁶, Kapil Kapur ⁷, David Sanders ⁸, Maria Eugenicos ⁹, Nigel Trudgill ¹⁰, Peter Whorwell ¹¹, John Mclaughlin ¹², Ayesha Akbar ¹³, Lesley Houghton ¹⁴, Phil G Dinning ¹⁵, Qasim Aziz ³, Alexander C Ford ^16 17, Amanda J Farrin ⁵, Robin Spiller ^1 2

Author information

¹NIHR Nottingham Digestive Diseases Biomedical Research Centre, University of Nottingham, Nottingham, UK.

²Nottingham Digestive Diseases Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK.

³Barts and The London School of Medicine and Dentistry, London, UK.

⁴Wingate Institute of Neurogastroenterology, Queen Mary University of London, London, UK.

⁵Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.

⁶Royal Stoke Hospital, University Hospitals of North Midlands NHS Trust, Stoke, UK.

⁷Barnsley Hospital, Barnsley Hospital NHS Foundation Trust, Barnsley, UK.

⁸Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.

⁹Western General Hospital Edinburgh, NHS Lothian, Edinburgh, UK.

¹⁰Sandwell General Hospital, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK.

¹¹Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK.

¹²Salford Royal University Hospital, Salford Royal NHS Foundation Trust, Manchester, UK.

¹³St Mark's Hospital, London North West Healthcare NHS Trust, London, UK.

¹⁴University of Leeds, Wellcome Trust Brenner Building, Level 9, St James's University Hospital, Leeds, UK.

¹⁵Discipline of Surgery and Gastroenterology, Flinders Medical Centre, Flinders University, Bedford Park, South Australia, Australia.

¹⁶Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK.

¹⁷Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK.

Abstract

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.