RecruitingPhase 3NCT05266807

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

Sponsor

Benoit Guery

Enrollment

220 participants

Start Date

Mar 15, 2023

Study Type

INTERVENTIONAL

Conditions

Clostridioides Difficile Infection

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.

Eligibility

Min Age: 18 Years

Inclusion Criteria16

Adults (≥18 years old) at the time of informed consent
Informed consent signature
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..
No multiple episodes (no more than 2 CDI episodes) within 3 last months.
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.
Willing and able to have FMT by capsule

Exclusion Criteria19

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.
Prior FMT within 6 months of randomization,
Prior colectomy, colostomy, ileostomy, or gastrectomy
Metronidazole already given for the treatment of the current CDI for more than 3 days,
Need for continued non-anti-CDI systemic antibiotics (should be stopped at randomization at the latest), except prophylactic doses of trimethoprim/sulfamethoxazole,
Anticipated indication for antibiotics treatment (for a non-CDI reason) in the next 8 weeks except prophylactic doses of trimethoprim/sulfamethoxazole
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)
Inflammatory bowel disease,
Patients with swallowing disorders, Zenker's diverticulum, gastroparesis, or prior small bowel obstruction,
Known hypersensitivity to vancomycin or fidaxomicin,
Pregnant/lactating women,
Estimated patient's life expectancy of less than 10 weeks,
Inability to follow protocol study procedures,
Inability to give informed consent,
Any condition or medications that will put the participant at greater risk from FMT according to the investigator,
Severely immunocompromised
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)

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Interventions

DRUGoral 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)

DRUGVancomycin or Fidaxomicin

Vancomycin or Fidaxomicin per os as initially prescribed per SoC