search
Back to results

Fecal Microbiota Transplantation in Clostridioides Difficile Infection First Episode and First Recurrence (FENDER)

Primary Purpose

Clostridioides Difficile Infection

Status
Recruiting
Phase
Phase 3
Locations
Switzerland
Study Type
Interventional
Intervention
oral capsulized Fecal Microbiota Transplantation
Vancomycin or Fidaxomicin
Sponsored by
Benoit Guery
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Clostridioides Difficile Infection focused on measuring Clostridioides difficile, Clostridium difficile, Fecal Microbiota Transplantation, Vancomycin, Fidaxomicin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

    1. 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 CDI test performed according to CDI diagnosis ESCMID guidelines
    2. 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 test performed according to CDI diagnosis ESCMID guidelines, with a mandatory toxin A/B EIA positive test and without reasonable evidence of another cause of diarrhea.
  4. No multiple episodes (more than one recurrence) of CDI that occurred 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. Complicated CDI (at least one of the following signs or symptoms are present and related to CDI: hypotension requiring vasopressors, intensive care unit admission for a complication of CDI, ileus leading to placement of nasogastric tube, toxic megacolon, colonic perforation, colectomy or colostomy)(2),
  2. Prior FMT within 6 months of randomization,
  3. Prior colectomy, colostomy, ileostomy, or gastrectomy.
  4. Metronidazole already given for the treatment of the first rCDI for more than 3 days,
  5. Need for continued non-anti-CDI systemic antibiotics,
  6. Anticipated indication for antibiotics treatment (for a non-CDI reason) in the next 8 weeks,
  7. Other infectious causes of diarrhea beyond CDI,
  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

Sites / Locations

  • CHUVRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

SoC + oral Fecal Microbiota Transplantation

SoC

Arm Description

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.

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

Outcomes

Primary Outcome Measures

Sustained clinical cure rate
Absence of CDI recurrence through 8 weeks after study treatment completion

Secondary Outcome Measures

Treatment failure
Early and late CDI recurrence rate
CDI new episodes
CDI new episodes occurence rate
Long-term clinical cure
Long-term clinical cure rate
Recurrence-free survival rate
Time from study intervention until CDI recurrence
Overall survival
Time from study intervention until death
Health status EQ-5D-5L measure (mobility, self-care, usual activities, pain/discomfort, annxiety/depression)
5-digit code (score from 1 to 5 for each digit, 1 representing no problem and 5 worse problem)
Health status EQ-5D-5L measure (patient's perception of overall health)
EQ Visual Analogue Scale (VAS) score (0 representing the worst health you can imagine to 100 representing the best health you can imagine)

Full Information

First Posted
February 18, 2022
Last Updated
May 1, 2023
Sponsor
Benoit Guery
search

1. Study Identification

Unique Protocol Identification Number
NCT05266807
Brief Title
Fecal Microbiota Transplantation in Clostridioides Difficile Infection First Episode and First Recurrence
Acronym
FENDER
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 16, 2022 (Actual)
Primary Completion Date
January 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Benoit Guery

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clostridioides Difficile Infection
Keywords
Clostridioides difficile, Clostridium difficile, Fecal Microbiota Transplantation, Vancomycin, Fidaxomicin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Randomized, Controlled, Open-label, Multicenter
Masking
None (Open Label)
Allocation
Randomized
Enrollment
220 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
SoC + oral Fecal Microbiota Transplantation
Arm Type
Experimental
Arm Description
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.
Arm Title
SoC
Arm Type
Active Comparator
Arm Description
Antibiotic (vancomycin 125 mg 4 times daily or fidaxomicin 200 mg 2 times daily, as initially prescribed per SoC) for 10 days.
Intervention Type
Drug
Intervention Name(s)
oral capsulized Fecal Microbiota Transplantation
Intervention Description
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
Intervention Name(s)
Vancomycin or Fidaxomicin
Intervention Description
Vancomycin or Fidaxomicin per os as initially prescribed per SoC
Primary Outcome Measure Information:
Title
Sustained clinical cure rate
Description
Absence of CDI recurrence through 8 weeks after study treatment completion
Time Frame
8 weeks after study treatment completion
Secondary Outcome Measure Information:
Title
Treatment failure
Description
Early and late CDI recurrence rate
Time Frame
Before 4 weeks and at 5-8 weeks after study treatment completion
Title
CDI new episodes
Description
CDI new episodes occurence rate
Time Frame
between 8 weeks and 12 months after study treatment completion
Title
Long-term clinical cure
Description
Long-term clinical cure rate
Time Frame
6 and 12 months after study treatment completion
Title
Recurrence-free survival rate
Description
Time from study intervention until CDI recurrence
Time Frame
12 months after study treatment completion
Title
Overall survival
Description
Time from study intervention until death
Time Frame
12 months after study treatment completion
Title
Health status EQ-5D-5L measure (mobility, self-care, usual activities, pain/discomfort, annxiety/depression)
Description
5-digit code (score from 1 to 5 for each digit, 1 representing no problem and 5 worse problem)
Time Frame
Baseline, 8 weeks, 6 and 12 months after study treatment completion
Title
Health status EQ-5D-5L measure (patient's perception of overall health)
Description
EQ Visual Analogue Scale (VAS) score (0 representing the worst health you can imagine to 100 representing the best health you can imagine)
Time Frame
Baseline, 8 weeks, 6 and 12 months after study treatment completion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 test performed according to CDI diagnosis ESCMID guidelines (Annex 20.1), with a mandatory 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 test performed according to CDI diagnosis ESCMID guidelines (Annex 20.1), with a mandatory 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 Criteria: Complicated CDI (at least one of the following signs or symptoms are present and related to CDI: hypotension requiring vasopressors, intensive care unit admission for a complication of CDI, ileus leading to placement of nasogastric tube, toxic megacolon, colonic perforation, colectomy or colostomy)(2), 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, Anticipated indication for antibiotics treatment (for a non-CDI reason) in the next 8 weeks, Other causes of acute or chronic diarrhea beyond CDI, 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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Benoit Guery, MD
Phone
+41213141643
Email
benoit.guery@chuv.ch
First Name & Middle Initial & Last Name or Official Title & Degree
Project Manager
Phone
+41795564371
Email
crc.fender@chuv.ch
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Benoit Guery
Organizational Affiliation
CHUV
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHUV
City
Lausanne
State/Province
Vaud
ZIP/Postal Code
1011
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Benoit Guery, MD
Email
benoit.guery@chuv.ch

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs