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

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 transplantation (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 pre-specified 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% CI [-11.7%, 17.7%]). Stratification by number of recurrences revealed no statistically significant differences. There were no clinically important differences in adverse events. CONCLUSIONS:FMT therapy vs. placebo did not reduce CDI recurrence or death at 56 days. There were no meaningful differences in adverse events between treatment groups.