ASEPTIC: primary antibiotic prophylaxis using co-trimoxazole to prevent SpontanEous bacterial PeritoniTIs in Cirrhosis—study protocol for an interventional randomised controlled trial
Dominic Crocombe,
Norin Ahmed,
Indran Balakrishnan,
Ekaterina Bordea,
Marisa Chau,
Louise China,
Lynsey Corless,
Victoria Danquah,
Hakim-Moulay Dehbi,
John F. Dillon,
Ewan H. Forrest,
Nick Freemantle,
David Peter Gear,
Coral Hollywood,
Rachael Hunter,
Tasheeka Jeyapalan,
Yiannis Kallis,
Stuart McPherson,
Iulia Munteanu,
Jim Portal,
Paul Richardson,
Stephen D. Ryder,
Amandeep Virk,
Gavin Wright,
Alastair O’Brien
Affiliations
Dominic Crocombe
UCL Institute of Liver and Digestive Health, Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust
Norin Ahmed
University College London Comprehensive Clinical Trials Unit
Indran Balakrishnan
Royal Free London NHS Foundation Trust, University College London
Ekaterina Bordea
University College London Comprehensive Clinical Trials Unit
Marisa Chau
University College London Comprehensive Clinical Trials Unit
Louise China
UCL Institute of Liver and Digestive Health, Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust
Lynsey Corless
Hull University Teaching Hospitals NHS Trust
Victoria Danquah
University College London Comprehensive Clinical Trials Unit
Hakim-Moulay Dehbi
University College London Comprehensive Clinical Trials Unit
John F. Dillon
Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee
Ewan H. Forrest
Gastroenterology Unit, Glasgow Royal Infirmary, University of Glasgow
Nick Freemantle
University College London Comprehensive Clinical Trials Unit
David Peter Gear
Cancer Research UK and UCL Cancer Trials Centre
Coral Hollywood
Gloucestershire Hospitals NHS Foundation Trust
Rachael Hunter
University College London Comprehensive Clinical Trials Unit
Tasheeka Jeyapalan
University College London Comprehensive Clinical Trials Unit
Yiannis Kallis
The Blizard Institute, Queen Mary University of London
Stuart McPherson
Liver Unit, The Newcastle Upon Tyne Hospitals NHS Foundation Trust, The Translational and Clinical Research Institute, Newcastle University
Iulia Munteanu
University College London Comprehensive Clinical Trials Unit
Jim Portal
University Hospitals Bristol NHS Foundation Trust
Paul Richardson
Liverpool University Hospitals NHS Foundation Trust
Stephen D. Ryder
NIHR Nottingham Biomedical Research Centre at Nottingham University Hospitals NHS Trust, University of Nottingham
Amandeep Virk
University College London Comprehensive Clinical Trials Unit
Gavin Wright
Mid & South Essex NHS Foundation Trust
Alastair O’Brien
UCL Institute of Liver and Digestive Health, Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust
Abstract Background Bacterial infection is a major cause of mortality in patients with cirrhosis. Spontaneous bacterial peritonitis (SBP) is a serious and common infection in patients with cirrhosis and ascites. Secondary prophylactic antibiotic therapy has been shown to improve outcomes after an episode of SBP but primary prophylaxis to prevent the first episode of SBP remains contentious. The aim of this trial is to assess whether primary antibiotic prophylaxis with co-trimoxazole improves overall survival compared to placebo in adults with cirrhosis and ascites. Methods The ASEPTIC trial is a multicentre, placebo-controlled, double-blinded, randomised controlled trial (RCT) in England, Scotland, and Wales. Patients aged 18 years and older with cirrhosis and ascites requiring diuretic treatment or paracentesis, and no current or previous episodes of SBP, are eligible, subject to exclusion criteria. The trial aims to recruit 432 patients from at least 30 sites. Patients will be randomised in a 1:1 ratio to receive either oral co-trimoxazole 960 mg or an identical placebo once daily for 18 months, with 6 monthly follow-up visits thereafter (with a maximum possible follow-up period of 48 months, and a minimum of 18 months). The primary outcome is overall survival. Secondary outcomes include the time to the first incidence of SBP, hospital admission rates, incidence of other infections (including Clostridium difficile) and antimicrobial resistance, patients’ health-related quality of life, health and social care resource use, incidence of cirrhosis-related decompensation events, liver transplantation, and treatment-related serious adverse events. Discussion This trial will investigate the efficacy, safety, and cost-effectiveness of co-trimoxazole for patients with liver cirrhosis and ascites to determine whether this strategy improves clinical outcomes. Given there are no treatments that improve survival in decompensated cirrhosis outside of liver transplant, if the trial has a positive outcome, we anticipate widespread adoption of primary antibiotic prophylaxis. Trial registration ClinicalTrials.gov NCT043955365 . Registered on 18 April 2020. Research ethical approval was granted by the Research Ethics Committee (South Central – Oxford B; REC 19/SC/0311) and the Medicines and Healthcare products Regulatory Agency (MHRA).
