Fecal microbiota transplantation (FMT) is safe and highly effective as first-line therapy for patients with first or second Clostridioides difficile infection, according to the first randomized, double-blind, placebo-controlled trial of its kind.
Study enrollment was halted after an interim analysis revealed significantly better outcomes among patients who received vancomycin plus FMT versus vancomycin alone, reported lead author Simon Mark Dahl Baunwall, MD, of Aarhus (Denmark) University Hospital and colleagues in The Lancet Gastroenterology & Hepatology.
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The investigators noted that the participants represented a real-world patient population, so the data support FMT “as a necessary, effective first-line option” in routine management of C. difficile infection.
“Previous studies have demonstrated clinical cure rates [with FMT] of up to 92%,” Dr. Baunwall and colleagues wrote. “Early use of FMT for first or second C. difficile infection has therapeutic potential, but no formal randomized trials to support use of the approach as a first-line therapy have been done.”
The present trial, conducted at a university hospital in Denmark, involved 42 adult patients with first or second C. difficile infection. Patients were randomized in a 1:1 ratio to receive either vancomycin alone or vancomycin plus FMT. All patients received 125 mg oral vancomycin four times daily for a minimum of 10 days after diagnosis. On day 1 after completion of vancomycin therapy and again between day 3 and 7, patients received either oral FMT or matching placebo, depending on their group. After completing the protocol, patients were followed for 8 weeks or C. difficile recurrence to evaluate resolution of C. difficile–associated diarrhea.
“In this trial, patients were treated with two sequential FMT procedures on separate days,” the investigators noted. “This practice might have overtreated some patients and differs from previous trials. It remains unknown whether optimal effect is achieved by one or two treatments.”
The trial design called for 84 patients, but enrollment was halted after an interim analysis of the above cohort of 42 patients because of significantly lower rate resolution in the placebo group. At the 2-month mark, 90% (95% confidence interval, 70%-99%) of patients in the FMT group had resolution, compared with only 33% (95% CI, 15%-57%) of patients in the placebo group (P = .0003), constituting a 57% (95% CI, 33%-81%) absolute risk reduction.
Most patients experienced adverse events, including 20 in the FMT group and all 21 in the placebo group, although most were transient and nonserious. The most common adverse events were diarrhea, which occurred more frequently in the FMT group (23 vs. 14 events), followed by abdominal pain(14 vs. 11 events) and nausea (12 vs. 5 events).
One limitation of the study was its single-center design with regional uptake; the authors noted that, despite having high statistical power for the clinical effect, the study’s premature termination and low patient number prevent inferences regarding mortality, time to effect, and cost.
“The results of this trial highlight how the use of fecal microbiota transplantation as a first-line treatment can effectively prevent C. difficile recurrence and suggests that microbiota restoration might be necessary to obtain sustained resolution,” the investigators wrote. “At present, only 10% of patients with multiple, recurrent C. difficile infection and indication for FMT receive it. International initiatives address the unmet need, but logistic and regulatory obstacles remain unsolved.”