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

This project is an SNF supported multicentric investigator initiated clinical trial involving 9 centers in Switzerland.

Clostridioides difficile (CD) is well known as major agent of healthcare-associated (HCA) 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. The risk of CDI recurrence increases from 25 to 45% from the first episode to the first recurrence, reaching 65% at the second recurrence. North American, as well as the European, guidelines propose vancomycin or fidaxomicin to treat a first episode or a first recurrence. 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. Baunwall et al. recently showed in a double-blind placebo controlled clinical trial that first line FMT after vancomycin for first or second CDI was superior to standard of care (vancomycin alone) to achieve CDI resolution at 8 weeks.

Rationale

The optimization of CDI treatment to obtain a sustained clinical cure is crucial. Few studies have focused on the early use of FMT. FMT 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 and effectiveness of FMT after standard treatment (vancomycin or fidaxomicin) compared to standard treatment alone (vancomycin or fidaxomicin) in patients with a first episode or a first recurrence of CDI.

The primary outcome is the efficacy (Per-Protocol – PP - population) and effectiveness (Intention-to-Treat - ITT - population) of FMT (combined with standard treatment) 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).

• Dre Tatiana Galpérine (FMT center)
• Dre Aurélie Ballif, Dr Dan Becker
• Valérie Sormani, CHUV, Lausanne
• Prof. Claire Bertelli, IMUL, CHUV, Lausanne
• Dre Vanessa Geib, Inselspital, Bern
• Prof. Rami Sommerstein, Luzern Hirslanden
• Dr Silvio Brugger, Universitätsspital, Zurich
• Prof. Sarah Tschudin, Universitätsspital, Basel
• Prof. Werner Albrich, Kantonsspital, St.Gallen
• Dre Veronique Erard, Hopital cantonal Fribourgeois, Fribourg
• Dr Christoph Andreas Fux, Kantonsspital Aarau