2022: The Gut Journal: RELIEVE IBS-D Double-Blind RCT
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GUT — BMJ Publishing Group · December 2022 · Named Top 10 Study of the Year
RELIEVE IBS-D: Double-Blind Randomised Controlled Trial of Enterosgel® for the Treatment of IBS with Diarrhoea
Prof. Yan Yiannakou · Prof. Peter Whorwell · Prof. John McLaughlin · Prof. Charles H Knowles · GUT Journal · 2022
Full citation
Double-blinded randomised placebo controlled trial of enterosgel (polymethylsiloxane polyhydrate) for the treatment of irritable bowel syndrome with diarrhoea (IBS-D).
Howell CA, Kemppinen A, Allgar V, Dodd M, Knowles CH, McLaughlin J, Pandya P, Whorwell P, Markaryan E, Yiannakou Y. Gut 2022;71:2430–2438. doi:10.1136/gutjnl-2022-327293. Named one of GUT journal’s top 10 studies of 2022. Presented at Digestive Disease Week 2022, San Diego.
Study design
How the trial was conducted
The RELIEVE IBS-D trial was a rigorous, double-blind, randomised, placebo-controlled, multicentre study conducted across 28 NHS sites in England — including GP practices, hospital outpatient departments, and the Functional Gut Clinic. It was registered on the ISRCTN registry (ISRCTN17149988), held MHRA reference CI/2018/0033, and was included on the NIHR portfolio (GAST 34032). The trial design was aligned with FDA guidance for clinical trials in IBS.
Trial phases
2-week screening phase
Participants assessed for eligibility and baseline symptom recording established via electronic diaries.
8-week double-blind phase
440 patients randomised to receive either Enterosgel® or placebo. Participants recorded stool consistency, pain, and global symptoms in e-diaries and questionnaires throughout.
8-week open-label and follow-up phase
393 patients continued into the open-label phase, during which all participants received Enterosgel®. 76% reported adequate relief of their IBS symptoms.
The trial became one of the UK’s first fully virtual interventional clinical trials during the Covid-19 pandemic — enabling patients nationwide to participate with no hospital visits and achieving recruitment 67% faster than traditional on-site methods.
Results
What the trial found
The primary outcome — a composite responder rate measuring simultaneous reduction in both abdominal pain and loose stools — showed 37.4% of Enterosgel patients responding versus 24.3% on placebo (OR 1.95, p=0.002). In the open-label phase, 76% of patients reported adequate relief of their IBS symptoms.
Primary outcome
37.4% vs 24.3%
Composite responder rate (pain + loose stools). OR 1.95, p=0.002.
Stool consistency
48.5% vs 32.5%
Statistically significant improvement (p<0.0001).
Open-label phase
76%
Of all patients reported adequate relief of IBS symptoms when taking Enterosgel.
Safety
0
Serious adverse events attributed to Enterosgel. Adverse event frequency similar in both groups.
Conclusion
A safe and effective treatment for IBS-D
Enterosgel® is safe and effective in IBS-D, providing an alternative to the limited current treatment options. The trial demonstrated that Enterosgel® significantly improves diarrhoea, pain, bloating, and urgency in people with IBS-D and increases overall quality of life.
“The RELIEVE IBS-D study showed that 76% of patients that took Enterosgel® reported adequate relief of their IBS symptoms. Enterosgel® is an effective treatment option for patients with IBS-D.”
Professor Yan Yiannakou — Chief Investigator, RELIEVE IBS-D · Consultant Neurogastroenterologist, County Durham & Darlington NHS Foundation Trust
The investigators
About the research team
Principal Investigators & Steering Committee — RELIEVE IBS-D Trial
Prof. Yan Yiannakou — Chief Investigator
Department of Gastroenterology, County Durham and Darlington NHS Foundation Trust, Darlington, UK. Director, NIHR Patient Recruitment Centre Newcastle. University of Teesside.
Prof. Peter Whorwell — Steering Committee
Neurogastroenterology Unit, Wythenshawe Hospital, Manchester, UK. Professor of Medicine & Gastroenterology, University of Manchester. One of the world’s foremost IBS researchers.
Prof. John McLaughlin — Steering Committee
Division of Diabetes, Endocrinology and Gastroenterology, The University of Manchester, Manchester, UK. Gastroenterology, Northern Care Alliance NHS Foundation Trust, Salford, UK.
Prof. Charles H Knowles — Steering Committee
Queen Mary University Faculty of Medicine and Dentistry, Blizard Institute, London, UK.
Independent Statistical Validation
Dr John Gregson, London School of Hygiene & Tropical Medicine. Data Monitoring Committee Chair: Dr Maria Eugenicos, University of Edinburgh.
Read the full clinical evidence for Enterosgel®
Including the RELIEVE IBS-D trial results, NHS Drug Tariff listing, and resources for healthcare professionals and patients.
View the research →References
- Howell CA, Kemppinen A, Allgar V, Dodd M, Knowles CH, McLaughlin J, Pandya P, Whorwell P, Markaryan E, Yiannakou Y. Double-blinded randomised placebo controlled trial of enterosgel (polymethylsiloxane polyhydrate) for the treatment of irritable bowel syndrome with diarrhoea (IBS-D). Gut 2022;71:2430–2438. doi:10.1136/gutjnl-2022-327293
- Newcastle Hospitals NHS Foundation Trust. Virtual trial discovers all-in-one treatment for patients with IBS-diarrhoea. June 2022. newcastle-hospitals.nhs.uk
- Health Research Authority. Enterosgel in the treatment of Irritable Bowel Syndrome with Diarrhoea. ISRCTN17149988.