293. Faecal microbiota transplant to ERadicate gastrointestinal carriage of Antibiotic Resistant Organism: a prospective, randomised placebo-controlled feasibility trial - The FERARO study (IRCTN reg. no. 34467677)

BACKGROUND: The gastrointestinal tract (GIT) is a reservoir of antibiotic resistant organisms (ARO). ARO colonisation precedes infections which are more challenging to treat than if drug susceptible, with excess morbidity and mortality. Presently, no effective GI decolonisation strategy exists. Faecal microbiota transplant (FMT) has emerged as a potential therapeutic. However, there is uncertainty about feasibility, safety and effectiveness. METHODS: Population: Patients with history of invasive infection with extended spectrum beta-lactamase (ESBL) or carbapenemase producing Enterobacterales (CPE) and evidence of persistent GIT ARO carriage (assessed by culture) INTERVENTION: 3 doses of encapsulated lyophilised FMT each manufactured from 80g raw stool given on consecutive days COMPARATOR: Matched placebo capsules OUTCOMES: Primary outcome - participant consent rate (as proportion of those approached screened for GIT carriage of ESBL-E/CPE). Secondary outcomes – safety and efficacy metrics including adverse event (AE) rates and GIT ARO carriage rates at 1 week, 1, 3 and 6 months. Exploratory outcomes – metagenomic and metabolomic stool analyses. RESULTS: Of 460 approached individuals, 124 (27%) consented. 53/124 participants (43%) fulfilled eligibility criteria. 44/53 (83%) randomised and 41/44 (93%) received investigational medicinal product (IMP): 20 FMT and 21 placebo. 39/41 (95%) completed dosing, 18/20 (90%) FMT (1 investigator and 1 participant discontinuation) and 21/21 (100%) placebo. Overall, GIT AE including reflux, bloating, change in bowel habit, were more common in FMT arm. 6 serious AE in 5 participants occurred in FMT arm, compared to 1 in placebo (all hospitalisation); none were deemed attributable to FMT. No unanticipated harms from FMT administration were realised. GIT ARO carriage rate assessed in 38/41 (93%) IMP recipients providing stool for analysis at 1-month was lower in FMT compared to placebo - FMT: 13/18 (72%) vs. placebo: 17/20 (85%), p=0.34. FERARO trial consort diagram [Figure: see text] ESBL/CPE detection rate [Figure: see text] Detected by culture over time CONCLUSION: Based on a priori assessment, a substantive trial would be feasible with protocol modifications. Encapsulated FMT appears safe intervention for eradication of GIT ARO carriage. Our feasibility trial informs design, and provides evidence to conduct future efficacy randomised controlled trials. DISCLOSURES: David Moyes, PhD, MSc, BSc, Pfizer: Grant/Research Support Simon D. Goldenberg, FRCPath, MD (Res), PGDipID, DipHIC, MSc, EnteroBiotix: Honoraria|Tillotts Pharma UK: Honoraria