Clostridioides Difficile InfectionPhase 3FENDERNCT05266807
Fecal Microbiota Transplantation in Clostridioides Difficile Infection First Episode and First Recurrence
A Phase 3 study testing oral capsulized Fecal Microbiota Transplantation and Vancomycin or Fidaxomicin in people with Clostridioides Difficile Infection, run by Benoit Guery at 8 sites in Switzerland.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Clostridioides Difficile Infection
- What is being tested?
- oral capsulized Fecal Microbiota Transplantation and Vancomycin or Fidaxomicin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 8 sitesSwitzerland
- Study dates
- 15 Mar 2023to 31 Jan 2028
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults (≥18 years old) at the time of informed consent
- Informed consent signature
- Medical record documentation of CDI defined as:
- 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,
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- 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
Who cannot join
- 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 total colectomy, colostomy, ileostomy, or gastrectomy
- Metronidazole already given alone for the treatment of the current CDI for more than 3 days,
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- 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)
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
Switzerland8 sites, 8 recruiting
- Recruiting
Universitätsspital
Basel, Basel, 4031
Sarah Tschudin-Sutter, MD, +41 61 328 6810, sarah.tschudin@usb.ch
- Recruiting
Inselspital Bern
Bern, Canton of Bern, 3010
Anna Eichenberger, MD, +41 31 632 88 44, anna.eichenberger@insel.ch
- Recruiting
HFR Fribourg - Hôpital cantonal
Fribourg, Canton of Fribourg, 1708
Véronique Erard, MD, +41 26 306 0836, veronique.erard@h-fr.ch
- Recruiting
CHUV
Lausanne, Canton of Vaud, 1011
Benoit Guery, MD, benoit.guery@chuv.ch
- Recruiting
Hirslanden Klinik St Anna
Lucerne, Canton of Lucerne, 6006
Rami Sommerstein, MD, 041 208 32 54, rami.sommerstein@hirslanden.ch
- Recruiting
Kantonsspital St Gallen, HOCH
Sankt Gallen, Canton of St. Gallen, 9007
Werner Albrich, MD, 071 494 2653, werner.albrich@h-och.ch
- Recruiting
Institut central des hôpitaux
Sion, Valais, 1950
Matthaios Papadimitriou Olivgeris, MD, +41 27 603 47 94, matthaios.papadimitriou-olivgeris@hospitalvs.ch
- Recruiting
Universitätsspital Zürich
Zurich, Canton of Zurich, 8091
Silvio Brugger, MD, +41 44 255 3402, silvio.brugger@usz.ch
About this study
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
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.
Read the 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 (100) 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
- Being tested
- oral capsulized Fecal Microbiota Transplantation, Vancomycin or Fidaxomicin
- Keywords
- Clostridioides difficile, Clostridium difficile, Fecal Microbiota Transplantation, Vancomycin, Fidaxomicin
- Medical subject headings
- Clostridium Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
oral capsulized Fecal Microbiota TransplantationDrug
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 FidaxomicinDrug
Vancomycin or Fidaxomicin per os as initially prescribed per SoC
| Study group | Role | What they receive |
|---|---|---|
| SoC + oral Fecal Microbiota Transplantation | Experimental | 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. Receives: Drug: oral capsulized Fecal Microbiota Transplantation; Drug: Vancomycin or Fidaxomicin |
| SoC | Active comparator | Antibiotic (vancomycin 125 mg 4 times daily or fidaxomicin 200 mg 2 times daily, as initially prescribed per SoC) for 10 days. Receives: Drug: Vancomycin or Fidaxomicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sustained clinical cure rate
Absence of CDI recurrence through 8 weeks after study treatment completion
Measured: 8 weeks after study treatment completion
Secondary outcomes (7)
Treatment failure
Early and late CDI recurrence rate
Measured: Before 4 weeks and at 5-8 weeks after study treatment completion
CDI new episodes
CDI new episodes occurence rate
Measured: between 8 weeks and 12 months after study treatment completion
Long-term clinical cure
Long-term clinical cure rate
Measured: 6 and 12 months after study treatment completion
Recurrence-free survival rate
Time from study intervention until CDI recurrence
Measured: 12 months after study treatment completion
Overall survival
Time from study intervention until death
Measured: 12 months after study treatment completion
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)
Measured: Baseline, 8 weeks, 6 and 12 months after study treatment completion
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)
Measured: Baseline, 8 weeks, 6 and 12 months after study treatment completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2022
- Study start15 Mar 2023
- Primary completion1 Apr 2027 (estimated)
- Study completion31 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Clostridioides Difficile InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, Controlled, Open-label, Multicenter
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Benoit Guery
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Benoit Guery, Centre Hospitalier Universitaire Vaudois
- Investigators
- Benoit Guery, Principal investigator, CHUV
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05266807
- Sponsor's protocol ID
- FENDER
- Acronym
- FENDER
- Status last verified
- Jul 2026
- First submitted
- 18 Feb 2022
- Last updated
- 10 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual de-identified participant data underlying the results reported in publications arising from this study will be made available, including demographic characteristics, baseline data, outcome measures, and relevant study variables. Individual participant microbiome sequencing data (raw sequence files and associated metadata) will be deposited in the European Nucleotide Archive (ENA). Data will be made available following publication and according to ENA access policies
Publications
Galperine T, Erard V, Sommerstein R, Albricht WC, Papadimitriou-Olivgeris M, Gubler M, Brugger SD, Tschudin-Sutter S, Moser M, Cagnon L, Ballif A, Becker D, Moser K, Guery B. Fecal microbiota transplantation versus vancomycin or fidaxomicin in Clostridioides difficile infection first episode and first recurrence: a study protocol for a randomised, controlled, open-label, multicentre phase III clinical trial. BMJ Open. 2026 Aug 28;16(8):e119480. doi: 10.1136/bmjopen-2026-119480.
PubMed 42665346