Randomised, double-blind, placebo-controlled trial of faecal microbiota transplantation in patients with decompensated cirrhosis: the Livergut protocol

Abstract

Abstract Introduction Cirrhosis represents the final stage of most chronic liver diseases and remains a major global cause of morbidity and mortality. Alterations in the gut microbiome correlate with disease severity and complications such as hepatic encephalopathy (HE) and acute-on-chronic liver failure (ACLF). Preliminary evidence suggests that faecal microbiota transplantation (FMT) is safe and could be effective in preventing disease progression, but data remain limited. Methods and analysis The LiverGut Trial is a phase III, multicentre, double-blind, placebo-controlled, randomised clinical trial designed to evaluate the safety and efficacy of FMT in patients with decompensated cirrhosis. A total of 190 adult patients (≥18 years) with decompensated cirrhosis will be enrolled across 8 Spanish tertiary hospitals. Participants will be randomised (1:1) to receive FMT or placebo capsules, administered orally in two treatment cycles (24 capsules per cycle, over two consecutive days) at entry into the study and at month 3. The primary endpoint is the time to the first new decompensation event (ascites, bacterial infection, gastrointestinal bleeding, HE or acute kidney injury). Ethics and dissemination The study protocol has been approved by the Ethics Committee of Hospital Clinic de Barcelona (HCB/2024/0805) and by the Spanish Agency for Medicines and Medical Devices through the Clinical Trial Information System (CTIS, European Union Clinical Trials No 2023-5 09 151-13-00) and will be conducted in accordance with the Declaration of Helsinki. The trial has been registered in ClinicalTrials.gov (NCT06533852). Results will be disseminated via CTIS, ClinicalTrials.gov, peer-reviewed journals and scientific conferences. Trial registration number EU CT No 2023-5 09 151-13-00 (protocol V.2.0, 25 February 2025); https://clinicaltrials.gov/study/NCT06533852.