Comparison Study Shows Efficacy in Frozen Fecal Product To Fresh For Fecal Microbiota Transplantation To Treat Recurrent C. diff. Infections

Frozen fecal microbiota transplantation showed efficacy comparable to fresh FMT for clinical resolution of diarrhea among adult patients with recurrent or refractory Clostridium difficile infection, according to results of a randomized trial published in JAMA.

Using frozen FMT would reduce costs associated with donor screening frequency, provide immediate availability of the treatment and enable delivery of the treatment to centers without on-site laboratory facilities,

the researchers wrote. “Previous studies have supported the use of frozen FMT for management of recurrent [C. difficile infection] but have not directly compared frozen with fresh FMT.”

Lee CH, et al. JAMA. 2016;doi:10.1001/jama.2015.18098

Malani PN, Rao K. JAMA. 2016;doi:10.1001/jama.2015.18100

Christine H. Lee, MD, from McMaster University in Canada, and colleagues, conducted a double-blind, noninferiority trial involving 232 adult patients with recurrent or refractory C. difficile infection (CDI) at six Canadian academic medical centers from July 2012 to September 2014. Patients were randomly assigned to receive frozen (n = 114) or fresh (n = 118) FMT via enema without bowel preparation, and if they showed no improvement by day 4, they received an additional FMT between days 5 and 8.

No recurrence of CDI-related diarrhea at 13 weeks and adverse events served as primary outcomes, and a 15% margin was set to confirm noninferiority.

In the per-protocol population (frozen, n = 91; fresh, n = 87), 83.5% of the frozen FMT group achieved clinical resolution compared with 85.1% of the fresh FMT group, a difference of – 1.6% (95% CI, – 10.5% to ∞; P = .01 for noninferiority). In the modified intention-to-treat population (frozen, n = 108; fresh, n = 111), 75% of the frozen FMT group achieved clinical resolution compared with 70.3% of the fresh FMT group, a difference of 4.7% (95% CI, – 5.2% to ∞; P < .001 for noninferiority). Adverse and serious adverse events were comparable between groups; the most common adverse events were transient diarrhea (70%), abdominal cramps (10%) or nausea (< 5%) during the 24 hours after FMT, and constipation (20%) and excess flatulence (25%) during follow-up, all mild to moderate in severity.

“Among adults with recurrent or refractory CDI, the use of frozen compared with fresh FMT did not result in worse proportion of clinical resolution of diarrhea,” the researchers concluded. “Given the potential advantages of providing frozen FMT, its use is a reasonable option in this setting.”

These researchers have provided

“the best evidence to date supporting the use of frozen stool, with their finding that use of frozen stool for FMT resulted in a rate of clinical resolution of diarrhea that was no worse than that obtained with fresh stool for FMT and will likely expand the availability of FMT for patients with recurrent CDI,”

Preeti N. Malani, MD, MSJ, associate editor of JAMA, and Krishna Rao, MD, MS, both from the University of Michigan Health System, Ann Arbor, wrote in a related editorial. “The ability to use frozen stool eliminates many of the logistical burdens inherent to FMT, because stool collection and processing need not be tied to the procedure date and time.

This study also provides greater support for the practice of using centralized stool banks, which could further remove barriers to FMT by making available to clinicians safe, screened stool that can be shipped and stored frozen and thawed for use as needed. In theory, procedure costs may also be decreased, since comprehensive donor screening is expensive.” – by Adam Leitenberger

Disclosures: Lee reports she has participated in clinical trials for ViroPharma, Actelion, Cubist and Merck, and served as a member of the advisory boards for Rebiotix and Merck. Please see the study for a full list of all other researchers’ relevant financial disclosures. Malani and Rao report no relevant financial disclosures.dR

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