EFFECTS OF LYOPHILIZED FECAL FILTRATE COMPARED TO LYOPHILIZED DONOR STOOL IN THE TREATMENT OF RECURRENT CLOSTRIDIOIDES DIFFICILE INFECTION: A MULTI-CENTER, DOUBLE-BLINDED RANDOMIZED TRIAL

Background: Fecal microbiota transplantation (FMT) is highly effective at preventing recurrent Clostridioides difficile infection (rCDI). Microbial engraftment is a key mechanisms mediating efficacy, but the importance of microbes has been questioned by two small studies showing efficacy of sterile fecal filtrate.
Aims: 1) determine if lyophilized sterile fecal filtrate (LSFF) is noninferior to lyophilized FMT (LFMT) in efficacy; 2) evaluate changes in patient reported health related quality of life (HRQOL); 3) understand patient preferences for different attributes of FMT.
Methods: This double-blind, non-inferiority (margin= 10%) study at 4 academic centers in Canada randomized rCDI patients to either LSFF or LFMT (1:1) between 2019 and 2023. Each treatment consisted of 15 oral capsules. Primary outcome was proportion of participants without CDI recurrence at 8 week. Secondary outcomes included 1) proportion of participants without CDI recurrence at week 24 weeks, 2) serious adverse events (mortality, hospitalization and infections related to treatments), and 3) minor adverse events (nausea, vomiting, abdominal pain and fever). Exploratory outcomes included changes in HRQOL and relative importance of different attributes of FMT.
Results: 137 participants were randomized (mean [SD] age, 61.2 [18.6] years; 89 women [65.4%]; mean CDI episodes 3.8) to LFMT group (66 participants) and LSFF (71 participants) group (Table 1). Prevention of rCDI 8 weeks after assigned treatment was achieved in 63.8% of participants in LSFF group and 86.9% in LFMT group (difference, -23.1%), resulting in trial termination. Serious adverse events were infrequent: 4 hospitalizations deemed not related and 1 hospitalization possibly related, and 1 death from COVID deemed not related to assigned treatment. Minor adverse events were self-limited and infrequent: nausea (6), vomiting (2), abdominal discomfort (15) and fever (2). Following successful treatment, participants had significant increases in EQ-5D-5L (n=99) VAS (median change: 10; p <0.001) and index value (median change: 0.04; p<0.001), and Cdiff32 (n=94) physical domain (median change: 16.07; p <0.001), mental domain (median change: 29.46; p<0.001), and social relationships domain (median change: 7.37; p<0.001). Work impairment decreased (n=21; median change: -10%; p<0.001) and activity impairment decreased (n=101; median change: -20%; p<0.001). Participants (n=103) indicated the 3 most important attributes of FMT were: treatment effectiveness, unknown risks of treatment and known risks of treatment.
Conclusions: Although LSFF was inferior to LFMT in preventing rCDI, statistically significant changes occured in HRQOL after successful treatment. Treatment effectiveness is the most important FMT attribute to participants. The result underscores the importance of viable microbes in mediating FMT efficacy.