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

NCT ID: NCT05266807

Last Updated: 2025-09-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 220 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-15
• Study Completion Date: 2028-01-31

Brief 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SoC + oral Fecal Microbiota Transplantation

Antibiotic (vancomycin 125 mg 4 times daily or fidaxomicin 200 mg 2 times daily, as initially prescribed per SoC) for 10 days, followed 12h to 4 days later by one oral FMT (20 capsules administered at D1 and 20 capsules at D2), and a second oral FMT if CDI is severe.

Group Type: EXPERIMENTAL

oral capsulized Fecal Microbiota Transplantation

Intervention Type: DRUG

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)

Vancomycin or Fidaxomicin

Intervention Type: DRUG

Vancomycin or Fidaxomicin per os as initially prescribed per SoC

SoC

Antibiotic (vancomycin 125 mg 4 times daily or fidaxomicin 200 mg 2 times daily, as initially prescribed per SoC) for 10 days.

Group Type: ACTIVE_COMPARATOR

Vancomycin or Fidaxomicin

Intervention Type: DRUG

Vancomycin or Fidaxomicin per os as initially prescribed per SoC

Interventions

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)

Intervention Type: DRUG

Vancomycin or Fidaxomicin

Vancomycin or Fidaxomicin per os as initially prescribed per SoC

Intervention Type: DRUG

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Benoit Guery

OTHER

Sponsor Role: lead

Responsible Party

Benoit Guery

Head physician

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Benoit Guery

Role: PRINCIPAL_INVESTIGATOR

CHUV

Locations

Universitätsspital

Basel, Basel, Switzerland

Site Status: RECRUITING

Inselspital Bern

Bern, Canton of Bern, Switzerland

Site Status: RECRUITING

HFR Fribourg - Hôpital cantonal

Fribourg, Canton of Fribourg, Switzerland

Site Status: RECRUITING

Kantonsspital St Gallen, HOCH

Sankt Gallen, Canton of St. Gallen, Switzerland

Site Status: RECRUITING

CHUV

Lausanne, Canton of Vaud, Switzerland

Site Status: RECRUITING

Universitätsspital Zürich

Zurich, Canton of Zurich, Switzerland

Site Status: RECRUITING

Institut central des hôpitaux

Sion, Valais, Switzerland

Site Status: RECRUITING

Countries

Switzerland

Central Contacts

Benoit Guery, MD

Role: CONTACT

benoit.guery@chuv.ch

+41213141643

Project Manager

Role: CONTACT

crc.fender@chuv.ch

+41795564371

Facility Contacts

Sarah Tschudin-Sutter, MD

Role: primary

sarah.tschudin@usb.ch

+41 61 328 6810

Anna Eichenberger, MD

Role: primary

anna.eichenberger@insel.ch

+41 31 632 88 44

Véronique Erard, MD

Role: primary

veronique.erard@h-fr.ch

+41 26 306 0836

Werner Albrich, MD

Role: primary

werner.albrich@h-och.ch

071 494 2653

Benoit Guery, MD

Role: primary

benoit.guery@chuv.ch

Silvio Brugger, MD

Role: primary

silvio.brugger@usz.ch

+41 44 255 3402

Matthaios Papadimitriou Olivgeris, MD

Role: primary

matthaios.papadimitriou-olivgeris@hospitalvs.ch

+41 27 603 47 94

Other Identifiers

FENDER

Identifier Type: -

Identifier Source: org_study_id