PROFIT, a PROspective, randomised placebo controlled feasibility trial of Faecal mIcrobiota Transplantation in cirrhosis: study protocol for a single-blinded trial

Abstract

Introduction: Patients with advanced cirrhosis have enteric bacterial dysbiosis and translocation of bacteria and their products across the gut epithelial barrier. This culminates in systemic inflammation and endotoxaemia, inducing innate immune dysfunction which predisposes to infection, and development of complications such as bleeding, sepsis and hepatic encephalopathy. This feasibility study aims to assess the safety of administering faecal microbiota transplantion to patients with cirrhosis and explore the effect of the intervention on their prognosis by achieving restoration of a healthy gut microbiome.

Methods and analysis: A PROspective, randomised placebo controlled feasibility trial of Faecal mIcrobiota Transplantation is a single-centre, randomised, single-blinded, placebo-controlled study evaluating faecal microbiota transplantation (FMT) against placebo. Patients with advanced but stable cirrhosis with a Model for End-Stage Liver Disease score between 10 and 16 will be recruited. Twenty-four patients will be randomised to FMT plus standard of care (as per our institutional practice) and eight patients to placebo in a ratio of 3:1. Patients will be evaluated at baseline before the study intervention is administered and at 7, 30 and 90 days post-intervention to assess safety and adverse events. FMT/placebo will be administered into the jejunum within 7 days of baseline. The primary outcome measure will be safety and feasibility as assessed by recruitment rates, tolerability and safety of FMT treatment. Results will be disseminated via peer-reviewed journals and international conferences. The recruitment of the first patient occurred on 23 May 2018.

Ethics and dissemination: Research Ethics approval was given by the London South East Research Ethics committee (ref 17/LO/2081).

Trial registration number: NCT02862249 and EudraCT 2017-003629-13.

Keywords: cirrhosis; faecal microbiota transplantation; feasibility; gut microbiota.

Conflict of interest statement

Competing interests: DS has received fees from Norgine, Falk and Shinogi, outside the submitted work. SG reports grants and personal fees from Astellas, personal fees from MSD, personal fees from Pfizer, personal fees from Shinogi, outside the submitted work.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.

Figures

Figure 1

Study flow chart and anticipated recruitment. FMT, faecal microbiota transplantation.

Figure 2

CI width around one proportion (P) by sample size (N) from PASS software V.15.