Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated diarrhoea in adults. Reported recurrence rates are approximately 15%–25% after a first episode and can rise to about 65% following multiple recurrences. Recurrent CDI is associated with increased morbidity, reduced quality of life, prolonged exposure to antimicrobials and greater healthcare utilisation.
Faecal microbiota transplantation (FMT) has demonstrated high efficacy for patients with multiple recurrent CDI. However, the benefit of introducing FMT earlier in the disease course — specifically after a first CDI episode in patients at higher risk of recurrence or after a first recurrence — has not been adequately studied. Emerging evidence suggests that earlier use of FMT may increase sustained clinical cure and lower recurrence, but robust randomised data are lacking. This trial tests whether adding oral FMT after standard antibiotic therapy improves outcomes compared with standard therapy alone.
This is a multicentre, randomised, open-label, pragmatic phase III superiority clinical trial performed across eight Swiss clinical centres. The protocol is designed to reflect real-world practice by using standard-of-care antibiotics before randomisation and by allowing pragmatic timing for FMT administration after antibiotics.
A total of 100 adult participants will be enrolled. The trial compares standard therapy alone to standard therapy followed by oral FMT, with primary analysis planned both per-protocol and by intention-to-treat.
Participants are adults who meet one of two clinical scenarios: either (1) a first episode of CDI accompanied by predefined risk factors for recurrence, or (2) a first CDI recurrence. All enrolled patients initially receive the local real-world standard-of-care anti-CDI antibiotics, consisting of 10 days of either vancomycin or fidaxomicin. Specific inclusion and exclusion criteria were not detailed in the source summary and therefore are not reported here.
After completion of the 10-day antibiotic course, participants are randomised 1:1 to one of two arms:
Intervention arm: oral FMT administered after the last antibiotic dose. For non-severe CDI the regimen is 15 to 20 oral FMT capsules given twice on two consecutive days, administered between 12 hours and 4 days after the final antibiotic dose. For participants with severe CDI, an additional 2-day FMT course is given. Exact donor screening, capsule preparation and storage procedures were not provided in the source summary.
Control arm: no additional treatment after completing the 10 days of standard antibiotic therapy. Participants in the control arm continue routine follow-up as per study protocol.
Participants who complete the standard 10-day antibiotic regimen are randomised in a 1:1 ratio to either receive adjunctive oral FMT or no further treatment. The trial is open-label; blinding procedures were not described in the source summary.
The primary endpoint is the proportion of patients who experience a CDI recurrence within 8 weeks after completion of treatment. Analyses will be conducted both per-protocol and on an intention-to-treat basis.
Secondary outcomes include:
Safety and tolerability are also prespecified secondary assessments.
The trial includes exploratory analyses aimed at understanding microbial and host factors associated with recurrence. These analyses will assess gut microbiota diversity and seek to identify biomarkers and immunologic or microbial predictors of CDI recurrence. Detailed methods for microbiota sequencing, biomarker assays and statistical approaches were not reported in the source summary.
Safety and tolerability of oral FMT following standard antibiotic therapy will be systematically assessed during follow-up. The source summary indicates that safety monitoring is part of the trial but does not provide granular details on adverse event definitions, grading scales, stopping rules or data monitoring committee procedures.
The study will be conducted in accordance with International Council for Harmonisation (ICH) Good Clinical Practice, the Declaration of Helsinki and Swiss regulatory standards. Trial results will be disseminated via peer-reviewed publications and conference presentations. The trial is registered under number NCT05266807.