New FMT Trial Halted Due to Effectiveness

Simon Mark Dahl Baunwall, MD

A new trial testing fecal microbiota transplantation (FMT) as a treatment for recurrent Clostridioides difficile infections (CDI) was stopped early because FMT was significantly more effective treating the disease than placebo.

A team, led by Simon Mark Dahl Baunwall, MD, Department of Hepatology and Gastroenterology, Aarhus University Hospital, compared the efficacy and safety of FMT compared to placebo following treatment with vancomycin for a first or second C difficile infection.

In the randomized, double-blind, placebo-controlled trial (EarlyFMT) the investigators consecutively screened 86 patients at a university hospital in Aarhus, Denmark between June 21, 2021 and April 1, 2022. Of the 86 screened patients, 42 were included in the intention-to-treat final analysis.

Each patient was at least 18 years old with a first or second C difficile infection, defined as at least 3 watery stools per day and a positive C difficile PCR test.

C Difficile Patients

Each patients was randomly assigned to either the FMT group (n = 21) or placebo (n = 21) administered on day 1 and between day 3-7, after they received 125 mg oral vancomycin 4 times daily for 10 days.

The investigators sought primary endpoints of the resolution of C difficile-associated diarrhea 8 weeks after treatment.

Each patient was followed up with for 8 weeks or until recurrence.

Stopping the Trial

However, the trial was stopped following the interim analysis on April 7, 2022 for ethical reasons because a significantly lower rate of resolution was found in the placebo group compared to the FMT group (Haybittle-Peto boundary limit P <0·001). The analysis shows 90% (n = 19; 95% CI, 70-99) of the FMT group and 33% (n = 7; 95% CI, 15-57) of the placebo group had a resolution of C difficile-associated diarrhea at week 8 (P = 0.0003).

There was an absolute risk reduction of 57% (95% CI, 33-81).

Adverse Events

For safety, 204 adverse events were identified, with 1 or more adverse events reported in 20 patients in the FMT group and all 21 patients in the placebo group. The most common adverse events were diarrhea (n = 23 in the FMT group; n = 14 in the placebo group) and abdominal pain (n = 14 in the FMT group; n = 11 in the placebo group).

The investigators also identified 3 serious adverse events potentially related to the treatment (n = 1 in the FMT group; n = 2 in the placebo group). However, no deaths or colectomies during the 8-week follow-up occurred.

“In patients with first or second C difficile infection, first-line fecal microbiota transplantation is highly effective and superior to the standard of care vancomycin alone in achieving sustained resolution from C difficile,” the authors wrote.

The study, “Fecal microbiota transplantation for first or second Clostridioides difficile infection (EarlyFMT): a randomized, double-blind, placebo-controlled trial,” was published online in The Lancet Gastroenterology & Hepatology.