Frozen vs Fresh Fecal Microbiota Transplantation and Clinical Resolution of Diarrhea in Patients With Recurrent Clostridium difficile Infection: A Randomized Clinical Trial.
- Frozen vs Fresh Fecal Microbiota Transplantation and Clinical Resolution of Diarrhea in Patients With Recurrent Clostridium difficile Infection: A Randomized Clinical Trial.
- sample size
P : patients with recurrent or refractory CDI
E : frozen-and-thawed (frozen, experimental) FMT
C : fresh (standard) FMT
In the mITT population the clinical resolution was 75.0% for the frozen FMT group and 70.3% for the fresh FMT group (difference, 4.7% [95% CI, -5.2% to ∞]; P < .001 for noninferiority).
There were no differences in the proportion of adverse or serious adverse events between the treatment groups.
T : Randomized, double-blind, noninferiority trial
A sample size of 156 (78 in each group) was calculated based on the assumed 85% efficacy of FMT and the attrition rate of 10%. Between-group comparisons were performed using Fisher exact test, proportional test, t test, and Wilcoxon test. All analyses were performed using R version 3.1.1 software.
First, the follow-up was limited to 13 weeks after the last FMT, which is insufficient to evaluate the long-term safety of the treatment. However, this time frame was longer than the majority of CDI therapeutic trials, which have followed up patients for up to 40 days.
Second, this study showed a lower proportion of clinical response in the per-protocol population following a single FMT (62%) than a previous study and the published case series, in which the cumulative cure rate was greater than 90%. Although this raises the possibility that small-volume enemas may be slightly less effective than other delivery methods, a direct comparative trial is needed to examine this. It is also likely that the larger sample size of the study, and its prospective, randomized design, allowed more sensitive detection of clinical failures; in addition, 51% of the patients were hospitalized at the time of FMT. The low number of stool donors may also be considered a study limitation; however, the aim was to compare fresh and frozen FMTs, rather than potential donor effects. Although it would have been useful to determine the efficacy of FMT according to the total number of recurrences, this was not feasible because of the prolonged duration of recurrence and the history of multiple recurrences in the majority of patients.