NCT05266807

Fecal Microbiota Transplantation in Clostridioides Difficile Infection First Episode and First Recurrence

Fecal Microbiota Transplantation Versus Vancomycin or Fidaxomicin in Clostridioides Difficile Infection First Episode or First Recurrence: A Randomized Controlled, Open-label, Multicenter Phase III Clinical Trial

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 220 (estimated)
• Sponsor: Benoit Guery · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The clinical trial aims to evaluate the efficacy of fecal microbiota transplantation (FMT) after standard of care treatment (either vancomycin or fidaxomicin) vs the pragmatic use of standard of care treatment (either vancomycin or fidaxomicin) in severe and non-severe first episode and first recurrence of Clostridioides difficile infection (CDI). Experimental arm: antibiotic treatment (vancomycin or fidaxomicin as initially prescribed per SoC continued for 10 days) followed by FMT by oral capsules (one FMT, i.e. 20 FMT capsules given on 2 consecutive days, and followed by a 2nd FMT in severe CDI). Control Arm: vancomycin or fidaxomicin as initially prescribed per SoC continued for 10 days.

Detailed description

Clostridioides difficile (CDI) is well known as major agent of healthcare-associated diarrhea in adult patients. One of the main challenges is the prevention of recurrence of Clostridioides difficile infection which occurs in 15-25% of the cases within the two months following the initial episode. A patient presenting a first recurrence has a higher risk of subsequent recurrences and may enter a cycle of multiple episodes of recurrence leading to significant morbidity, decrease in quality of life, and long courses of antimicrobial therapy. North-American, as well as the European, guidelines propose vancomycin or fidaxomicin to treat this first recurrence. All these recommendations rely on weak to moderate quality of evidence. For patients with multiple recurrences, fecal microbiota transplantation (FMT) is recommended as an option in guidelines based on several randomized controlled trials and a meta-analysis having shown superior efficacy compared to antibiotics with regard to preventing further recurrences. FMT has never been evaluated for CDI first episode and first recurrence and could represent an attractive treatment to prevent further recurrences, avoid hospitalization (mean length of 10 days) and reduce overall mortality risk. The aim of our study is to compare the efficacy of FMT (combined with standard treatment: vancomycin or fidaxomicin) compared to standard treatment (vancomycin or fidaxomicin) in patients with a first CDI episode presenting risk factors for recurrence and in patient with a first CDI recurrence. This is a multicenter, randomized, open-label, phase III superiority trial comparing fecal microbiota transplantation (FMT) delivered via oral capsules after a conditioning standard antibiotic treatment (either vancomycin or fidaxomicin), to the pragmatic use of standard treatment (either vancomycin or fidaxomicin) in non-severe and severe CDI first episode or first recurrence. Patients (220) will be randomized 1:1. Patients randomized in the FMT arm (Arm A) will continue the antibiotic treatment (vancomycin or fidaxomicin initially prescribed as SoC) for a total of 10 days. The antibiotic will be stopped for 12h to 4 days and then all patients will receive a first FMT on 2 consecutive days (20 capsules at D1 and 20 capsules at D2). Patients with severe CDI will receive a second FMT immediately administrated at D3 (20 capsules) and at D4 (20 capsules). Patients randomized in the standard treatment arm (Arm B) will continue the antibiotic treatment (vancomycin or fidaxomicin initially prescribed as SoC) for a total of 10 days. Efficacy of FMT (combined with standard treatment) will be assessed by comparing the proportion of participants experiencing clinical cure 8 weeks after study treatment completion, in the FMT intervention arm (arm A) and in the standard of care control arm (arm B). Participants will be followed for 12 months.

Conditions

• Clostridioides Difficile Infection

Interventions

Type	Name	Description
DRUG	oral capsulized Fecal Microbiota Transplantation	FMT will be administered per os in the form of capsules containing faeces from a healthy donor. Capsules are manufactured at the CHUV pharmacy (University Hospital of Lausanne, Switzerland)
DRUG	Vancomycin or Fidaxomicin	Vancomycin or Fidaxomicin per os as initially prescribed per SoC

Timeline

• Start date: 2023-03-15
• Primary completion: 2027-04-01
• Completion: 2028-01-31
• First posted: 2022-03-04
• Last updated: 2025-09-18

Locations

7 sites across 1 country: Switzerland