Reviewed by Sara Karaba, MD, PhD, MHS, Johns Hopkins University
Bottom line: A randomized trial from the VA system (MATCH study) demonstrated that oral capsule fecal microbiota transplant (FMT) did not lead to a reduction in recurrent C. difficile infection (CDI).
There are several observational studies and two prior small randomized controlled trials examining the use of FMT to treat recurrent CDI. These prior studies, many with FMT delivered via colonoscopy, enema, or via upper GI tract suggested lower rates of recurrent CDI. However, a new centrally-operated, randomized, double-masked and placebo-controlled to assess the efficacy and safety of capsule-delivered FMT. This trial included 153 patients after initial successful treatment of recurrent CDI (at least 1 recurrence, average time between end of antimicrobial treatment and randomization 6.6 days) between October 2018-July 2022, and was stopped due to futility after meeting pre-specified criteria. There was no difference in the primary endpoint of diarrhea and possible or definite CDI recurrence between the FMT arm (25/76, 32.9%) and placebo arm (23/77, 29.9%). When evaluated by one recurrence vs two or more prior to randomization or by definite vs possible recurrence within the trial there were also no differences, nor was there a difference in death within 56 days (absolute difference 3.0%, 95% CI -11.7-17.7%). This study included patients with 1 recurrence (78% of patients), while patients in other studies often had many recurrent episodes, potentially explaining a lack of benefit. While well-tolerated and safe, in this pragmatic and randomized trial, it seems that FMT delivered via capsule did not reduce the risk of CDI recurrence or death.
Reference: Drekonja DM, Shaukat A, Huang Y, Zhang JH, Reinink AR, Nugent S, Dominitz JA, Davis-Karim A, Gerding DN, Kyriakides TC. A randomized controlled trial of efficacy and safety of Fecal Microbiota Transplant for preventing recurrent Clostridioides difficile infection. Clin Infect Dis. 2024 Sep 13:ciae467. doi: 10.1093/cid/ciae467. Epub ahead of print. PMID: 39271107.