A Randomized Controlled Trial of Efficacy and Safety of Fecal Microbiota Transplant for Preventing Recurrent Clostridioides difficile Infection

Dimitri M Drekonja, Aasma Shaukat, Yuan Huang, et al

Clinical Infectious Diseases, Volume 80, Issue 1, 15 January 2025, Pages 52–60, https://doi.org/10.1093/cid/ciae467

Abstract

Background

Clostridioides difficile infection (CDI) is the most common cause of healthcare–associated infections in US hospitals, with 15%–30% of patients experiencing recurrence. The aim of our randomized, double-blind clinical trial was to assess the efficacy of capsule-delivered fecal microbiota transplant (FMT) versus placebo in reducing recurrent diarrhea and CDI recurrence. The secondary aim was FMT safety assessment.

Methods

Between 2018 and 2022, Veterans across the Veterans Health Administration system with recurrent CDI who responded to antibiotic treatment were randomized in a 1:1 ratio to oral FMT or placebo capsules. Randomization was stratified by number of prior CDI recurrences (1 or ≥2). The primary endpoint was clinical recurrence by day 56, defined as >3 unformed stools daily for ≥2 days with or without laboratory confirmation of C. difficile, or death within 56 days.

Results

The study was stopped due to futility after meeting prespecified criteria. Of 153 participants (76 FMT, 77 placebo) with an average age of 66.5 years, 25 participants (32.9%) in the FMT arm and 23 (29.9%) in the placebo arm experienced the primary endpoint of diarrhea and possible or definite CDI recurrence or death within 56 days of capsule administration (absolute difference, 3.0% [95% confidence interval, −11.7% to 17.7%]). Stratification by number of recurrences revealed no statistically significant differences. There were no clinically important differences in adverse events.

Conclusions

FMT therapy versus placebo did not reduce CDI recurrence or death at 56 days. There were no meaningful differences in adverse events between treatment groups.

Clinical Trials Registration

NCT03005379.