P: 12 PROFIT: PROspective, Randomised Placebo-controlled Feasibility Trial of Faecal Microbiota Transplantation in Cirrhosis Interim Analysis

Abstract

BACKGROUND: Patients with cirrhosis have intestinal dysbiosis and small bowel bacterial overgrowth, with enhanced gut permeability, allowing translocation of pathogen-associated molecules and viable bacteria into the systemic circulation. Faecal Microbiota Transplantation (FMT) seeks to replace the dysbiotic flora with healthy microbes, to reduce systemic inflammation and improve transplant-free outcomes. PROFIT is a single-blinded randomised placebo-controlled trial of FMT in 32 patients with advanced stable cirrhosis. The primary outcome of the study was to assess the safety and feasibility of a single naso-jejunally administered FMT or placebo (3:1 allocation) in patients with a MELD score between 10 and 16. METHODS: To date eighteen patients have been treated (FMT n = 13; placebo n = 5). 71% of those treated were male [mean age 54.4 years (range 38–75) and mean MELD 12.88 (range 10–16)]. Patients continued lactulose, but were required to discontinue all antibiotics, including rifaximin, two weeks prior to treatment. Following bowel preparation with Moviprep®, 200 mL FMT/placebo was delivered via naso-jejunal tube in to the proximal jejunum at gastroscopy. Patients were assessed for adverse events and underwent clinical review at day 7, 30 and 90 with biobanking of stool, saliva, urine, whole blood and plasma for quantitative metagenomics, metabonomics, bacterial DNA quantification, bile acids, whole blood culture in response to endotoxin and plasma cytokines and leucocyte function testing at a later date. RESULTS: The FMT has been well tolerated and the five serious adverse events (SAEs) reported requiring hospital admission (placebo n = 1; FMT n = 4) were not treatment-related. Biochemistry, leucocyte count and MELD score did not change. Mean venous ammonia reduced at day 30 in the FMT cohort [71.67 μmol/L (95% CI 54.43–88.9) day 0 versus 51.22 μmol/L (CI 35.18–67.26) day 30] whereas it increased in the placebo group [54.4 μmol/L (95% CI 38.17–70.63) day 0 versus 73.25 μmol/L (95% CI 22.54–124) at day 30]. Figure 1 shows a reduction in delta ammonia at day 7 [mean −1.15 (−16.23 to 13.73 95% CI)] versus day 30 [−15.11 (−2.82 to −27.4) post FMT. CONCLUSIONS: The interim analysis shows that nasojejunally administered FMT appears safe and well tolerated in patients with advanced cirrhosis and reduces venous ammonia at day 30.