HONOLULU – Fecal transplant was shown to be effective in the treatment of recurrent or refractory episodes of Clostridium difficile infection in a double-blind trial for the first time, and a second study isolated predictors of treatment failure.
The results of the double-blind study were expected. Several studies, although none double blind, have previously shown this therapy to be efficacious. The study of predictors of failure may be of more immediate practical application, because it is relevant to patient selection, according to the investigators, some of whom were involved in both studies.
In the double-blind study, 46 patients were randomized at two centers to receive a fecal microbiota transplant from donor stool or to a placebo, which was a transplant of the patient’s own stool.
The primary outcome was clinical cure at the end of 8 weeks, achieved in 91% of those randomized to the active therapy and 63% of those randomized to placebo (P = .024). Most of those who had treatment failure, which occurred on average 10 days after the procedure (range, 1-62 days), received the active therapy subsequently and also achieved clinical cure after donor transplantation.
Dr. Colleen Kelly
“There were no significant differences in any adverse event rates between the donor transplant and placebo groups,” Dr. Colleen Kelly reported at the annual meeting of the American College of Gastroenterology. Dr. Kelly, a gastroenterologist with the Miriam Hospital, Brown University, Providence, R.I., was also a coauthor of the study of risk factors for the failure of fecal transplant.
Underlining the importance of a double-blind trial to provide confirmation of the efficacy of fecal transplant, Dr. Christina M. Surawicz, who moderated the ACG session at which both studies were presented, said, “We have been waiting for these results.”
However, a disparity in results at the two participating centers is notable. In Providence, cure was achieved in 90% of those receiving fecal transplant versus 43% receiving placebo (P = .019). At the other participating institution, Montefiore Medical Center, New York, the cure rate was 92% with fecal transplant, but 90% of the placebo patients were also cured (P = .89). The data were not intended for a separate analysis, so Dr. Kelly said this did not affect her final conclusion that this trial confirmed the efficacy of this treatment.
In the separate study evaluating predictors of failure to achieve cure after fecal transplant, the retrospective analysis was performed with 345 patients treated for C. difficile infection with fecal transplant. In this population, the overall failure rate was 23.7%, but there was a wide variability observed upon univariate and multivariate analysis of risk factors, Dr. Monika Fischer, a gastroenterologist at Indiana University Hospital, Indianapolis, said at the meeting.
For example, in patients with nonsevere recurrent C. difficile infection, the failure rate was 18%. In contrast, the failure rate was approximately 50% among those with severe refractory C. difficile infection.
Upon multivariate analysis, three risk factors were independent predictors of fecal transplant failure: inpatient status, which was associated with an odds ratio of 6.92 (P = .001); being immunosuppressed (OR, 3.28; P = .0004); and previous hospitalization for C. difficile infection (OR, 1.45 for each prior hospitalization; P less than .001).
With the use of these three factors, a risk score was found to be highly predictive of failure. In this risk score, 5 points were attributed to inpatient status, 3 points to immunosuppression, and 1 point to each prior hospitalization for C. difficile infection. On a scale of 0-12 points, the risk of failure was 13% in those with 0 points, 17% in those with 1-3 points, and 44% in those with 4 or more points.
“Our data suggest that the risk of fecal transplant failure is predictable based on pretransplant characteristics. We hope that this risk stratification model will prove helpful,” said Dr. Fischer, whose coauthors included Dr. Kelly.
Although she did not directly endorse this risk stratification tool for patient management, Dr. Surawicz called this presentation “very clinically relevant.” Practical tools are needed to guide the use of this therapy as it becomes more widely used in the treatment of C. difficile, said Dr. Surawicz, professor of gastroenterology, University of Washington, Seattle.
Dr. Kelly reported no relevant financial conflicts. Dr. Fischer reported a financial relationship with Rebiotix.