Using fecal microbiota transplantation to treat Clostridioides difficile infections

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

This study is testing if a new treatment using fecal microbiota transplantation can help people with their first Clostridioides difficile infection or its first recurrence feel better and prevent future infections after standard antibiotic treatment.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 220 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Centre Hospitalier Universitaire Vaudois (Academic / other)
• Locations: 7 sites (Basel, Basel and 6 other locations)
• Trial ID: NCT05266807 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of fecal microbiota transplantation (FMT) following standard antibiotic treatment (vancomycin or fidaxomicin) in patients experiencing their first episode or first recurrence of Clostridioides difficile infection (CDI). Participants will receive either the standard treatment alone or the standard treatment followed by FMT using oral capsules. The study aims to determine if FMT can reduce the risk of further CDI recurrences compared to standard antibiotic therapy alone. This approach is based on previous evidence suggesting FMT is effective for patients with multiple recurrences but has not been tested for first episodes or first recurrences.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a first episode of CDI and risk factors for recurrence.

Not a fit: Patients who have had multiple CDI episodes or those without risk factors for recurrence may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the recurrence of Clostridioides difficile infections and improve patient outcomes.

How similar studies have performed: Previous studies have shown that fecal microbiota transplantation is effective for recurrent CDI, but this specific application for first episodes and first recurrences is novel.

Eligibility criteria

Inclusion Criteria:

1. Adults (≥18 years old) at the time of informed consent
2. Informed consent signature
3. Medical record documentation of CDI defined as:

   a. A first CDI episode associated with risks factors for recurrence, defined as: i. No CDI episode within the last 8 weeks ii. Current combination of CDI signs and symptoms, confirmed by medical record documentation of microbiological evidence of C. difficile toxin and C. difficile in stools shown by a CDI PCR positive test with Ct \< 25 or a toxin A/B EIA positive test and without reasonable evidence of another cause of diarrhea, iii. Presenting at least one of the following risks factors for CDI recurrence:
   * age \>65 years-old,
   * hospitalization within the last 3 months,
   * use of proton pump inhibitors (PPI) within the last 3 months,
   * Charlson comorbidity index (CCI) \>2,
   * living in long term facility,
   * healthcare- associated CDI (see definition in section 7),
   * severe CDI episode (see definitions in section 6.1.2),
   * immunocompromised patient (except severely immunocompromised according to definitions in section 7.1),
   * history of prior CDI episode(s) (more than 8 weeks ago). OR b. A first CDI recurrence, defined as: i. Previous episode of treated and cured CDI within the last 8 weeks confirmed by medical record documentation of a clinical picture of CDI combined with a positive microbiological CDI test performed according to CDI diagnosis ESCMID guidelines ii. Current combination of CDI signs and symptoms, confirmed by medical record documentation of microbiological evidence of C. difficile toxin and C. difficile in stools shown by a CDI PCR positive test with Ct \< 25 or a toxin A/B EIA positive test , and without reasonable evidence of another cause of diarrhea..
4. No multiple episodes (no more than 2 CDI episodes) within 3 last months.
5. Already taking since less than 10 days or will start a course of antibiotics (vancomycin or fidaxomicin) to control recurrent CDI symptoms at the time of screening.
6. Willing and able to have FMT by capsule

Exclusion Criteria:

1. Severe-complicated CDI if at least one of the following signs or symptoms are:

   * ongoing at time of screening and related to CDI: hypotension, septic shock, elevated serum lactate, ileus,
   * or were present at any time of the CDI episode and related to CDI: toxic megacolon, bowel perforation, or any fulminant course of disease (i.e. rapid deterioration of the patient.
2. Prior FMT within 6 months of randomization,
3. Prior colectomy, colostomy, ileostomy, or gastrectomy
4. Metronidazole already given for the treatment of the current CDI for more than 3 days,
5. Need for continued non-anti-CDI systemic antibiotics (should be stopped at randomization at the latest), except prophylactic doses of trimethoprim/sulfamethoxazole,
6. Anticipated indication for antibiotics treatment (for a non-CDI reason) in the next 8 weeks except prophylactic doses of trimethoprim/sulfamethoxazole
7. Other causes of chronic or acute diarrhea beyond CDI (chronic diarrhea is defined as loose/watery stools, which occur three or more times within 24 hours and last for 4 or more weeks)
8. Inflammatory bowel disease,
9. Patients with swallowing disorders, Zenker's diverticulum, gastroparesis, or prior small bowel obstruction,
10. Known hypersensitivity to vancomycin or fidaxomicin,
11. Pregnant/lactating women,
12. Estimated patient's life expectancy of less than 10 weeks,
13. Inability to follow protocol study procedures,
14. Inability to give informed consent,
15. Any condition or medications that will put the participant at greater risk from FMT according to the investigator,
16. Severely immunocompromised
17. No response to anti-CDI antibiotic treatment after at least 5 days of treatment (i.e. no diminution of the daily number of stools at BSS 6-7 compared to first day of treatment; or worsening of CDI severity parameters)

Where this trial is running

Basel, Basel and 6 other locations

• Universitätsspital — Basel, Basel, Switzerland (Recruiting)
• Inselspital Bern — Bern, Canton of Bern, Switzerland (Recruiting)
• HFR Fribourg - Hôpital cantonal — Fribourg, Canton of Fribourg, Switzerland (Recruiting)
• Kantonsspital St Gallen, HOCH — Sankt Gallen, Canton of St. Gallen, Switzerland (Recruiting)
• Chuv — Lausanne, Canton of Vaud, Switzerland (Recruiting)
• Universitätsspital Zürich — Zurich, Canton of Zurich, Switzerland (Recruiting)
• Institut central des hôpitaux — Sion, Valais, Switzerland (Recruiting)

Study contacts

• Principal investigator: Benoit Guery — Chuv
• Study coordinator: Benoit Guery, MD

Conditions Clostridioides Difficile Infection; Clostridioides difficile; Clostridium difficile; Fecal Microbiota Transplantation; Vancomycin; Fidaxomicin