A51 EFFECT OF LYOPHILIZED STERILE FECAL FILTRATE VS LYOPHILIZED DONOR STOOL ON RECURRENT CLOSTRIDIUM DIFFICILE INFECTION (RCDI): PRELIMINARY RESULTS FROM A RANDOMIZED, DOUBLE-BLIND PILOT STUDY. (15th March 2019) - Kao, D H
Abstract: Background: Fecal microbial transplantation (FMT) has been shown to be a highly effective therapy for rCDI. Success rate is > 90%. A recent study using sterile fecal filtrate successfully prevented CDI recurrence in 5 patients, suggesting live microbes may not be required for efficacy. Aims: To determine whether live microbes are necesary for the clinical efficacy of FMT by comparing treatment outomces in rCDI patients receiving either lyophilized sterile fecal filtrate (LSFF) or lyophilized FMT (LFMT). Primary outcome: proportion of patients in each group with no CDI recurrence at week 8. Secondary outcomes: mortality rate and infections directly attributable to CDI or treatment at week 8. Methods: In this single center pilot study, eligible participants with rCDI were randomized to LSFF or LFMT at 1:1. Inclusion criteria: age > 18 years; diagnosis of at least 3 episodes of RCDI, each episode defined by presence of diarrhea (≥3 unformed stools/24 h), positive for C. difficile toxin, episodes occurring within 2 months of each other after finishing anti-CDI therapy, and recurring diarrhea after symptom resolution following at least 10 d of anti-CDI therapy; CDI infection under symptomatic control with < 3 loose/unformed stools/24 h for at least 2 consecutive days before treatment; and d) ability to provide informed consent. Exclusion criteria: fulminant CDI; chronic diarrheal illness; taking or planning to take investigational drug within 3 months of enrolment; dysphagia; ileus or bowel obstruction, pregnancy; active infection requiring antibiotic therapy; or life expectancy <6 months. Each patient received a single dose of 15 capsules of LFMT or LSFF according to group assigned, under direct observation in clinic. All capsules appeared identical. All patients were seen in the clinic at screening, at week 0 for treatment, and 1, 4, 8 and 24 weeks after treatment. Recurrence of diarrhea ( ≥3 unformed bowel movements/24 h) was evaluated at each follow-up and tested for C difficile. In the event that the first assigned treatment failed to prevent CDI recurrence, open-label FMT was offered. Results: Between Feb 15 and Aug 1, 2019, 4 participants were randomized to the LSFF group and 5 to the LFMT group (table 1). Primary outcome was achieved by 75% (3/4) of the LSFF group and 80% (4/5) of the LFMT group. Both failure cases received a single dose of open-label LFMT and achieved cure. No mortality or FMT-related infections were observed. Conclusions: Our preliminary findings suggest live microbes may not be necessary for the clinical efficacy of FMT in treating rCDI. Further characterization of sterile filtrate and mechanistic studies will lay the foundation for development of refined microbiome-derived therapy for rCDI. Funding Agencies: University of Alberta Hospital Foundation