Fecal microbiota transplantation versus vancomycin or fidaxomicin in

introductionMETHODS AND ANALYSIS: This is a multicentre, randomised, open-label, pragmatic phase III superiority clinical trial conducted across eight Swiss clinical centres. A total of 100 adults will be enrolled. Patients with either (1) a first CDI episode and risk factors for recurrence or (2) a first CDI recurrence and who first receive the real-world standard of care anti-CDI antibiotics (10 days of vancomycin or fidaxomicin) are randomised 1:1 to oral FMT following standard antibiotic therapy or standard therapy alone. The intervention group receives within 12 hours to 4 days of the last antibiotics administration, 15 to 20 oral FMT capsules twice on two consecutive days if the CDI is non-severe; those with severe CDI receive an additional 2-day FMT course. The control group does not receive any additional treatment after completing the 10 days of standard therapy. The primary endpoint is the proportion of patients having experienced a CDI recurrence at 8 weeks post completion of treatment (assessed per-protocol and intention-to-treat). Secondary outcomes include early and late recurrence rates, sustained cure at 6 and 12 months, quality-adjusted life years, recurrence-free and overall survival at 12 months. Exploratory analyses include microbiota diversity, biomarker identification and assessment of immunologic and microbial predictors of recurrence. Safety/tolerability is also assessed. ETHICS AND DISSEMINATION: The study will be conducted in accordance with International Council for Harmonisation Good Clinical Practice, the Declaration of Helsinki and Swiss regulatory standards. Results will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT05266807.