Fecal Transplantation to Eradicate Colonizing Emergent Superbugs

NCT05035342 | Recruiting Phase 3 DMC

• 2 other identifiers: APHP1805872019-004402-10
• Study Type: interventional
• Target: 214
• Locations: 1 country
• Sites: 11

Brief Summary

Carriage of multi-drug and extensive-drug resistant Gram negative bacteria (MDR-GNB) is associated with an increased risk of infections by these bacteria for the carriers and a high risk of dissemination both in the healthcare setting and the community; the main MDR-GNB reservoir is the fecal microbiota. To prevent both infections and dissemination, effective measures to decolonize subjects carrying MDR-GNB are urgently needed. Animal models, case reports and cohort studies suggest fecal microbiota transplantation (FMT) may be efficient for MDR-GNB decolonization.

Conditions

Enterobacteriaceae Infections; Fecal Microbiota Transplantation

Outcome Measures

Primary Outcomes (1)

• Determine whether FMT with frozen capsules is effective for decolonization of MDR-GNB.

  Proportion of subjects not carrying MDR-GNB (neither ESBL-E nor CRE) at day 30 (±10 days) after randomization as determined by culture methods

  30 days post-randomization

Secondary Outcomes (10)

• Prevention of infections

  90 days post-randomization

• Prevention of infections

  90 days post-randomization

• Prevention of infections

  up to 2 years post-randomization

• Prevention of infections

  up to 2 years post-randomization

• Safety and tolerability of FMT

  2 years post-randomization

Study Arms (2)

Fecal microbiota Transplant (FMT)

EXPERIMENTAL

Fecal microbiota Transplant (FMT) prepared from the stools of healthy donors diluted in 80% glycerol used as bacterial cryoprotectant, blenderized, sieved and centrifuged (4°C, 4000 tr/min, 20 min) and manufactured in capsules (n=50 capsules corresponding to approximately 50 grams of stool; 50 in one day).

Biological: Fecal Microbiota Transplantation (FMT) capsules

Placebo of FMT

PLACEBO COMPARATOR

FMT vehicle (solution of saline (NaCl 0.9%)) with 80% glycerol (storage in the same conditions as preparation for FMT experimental group) administered at the same volume and same time point as the experimental group.

Biological: Placebo capsules

Interventions

Fecal Microbiota Transplantation (FMT) capsules BIOLOGICAL

Donated fecal matter will be sequentially diluted in 80% glycerol used as bacterial cryoprotectant, blenderized, sieved and centrifuged (4°C, 4000 tr/min, 20 min). The pellet is resuspended and manually pipetted into size 0 capsules (650 μL), which are closed and then secondarily sealed in size 00 capsules (hypromellose capsules, DR caps from Capsugel®, MA). Each capsule contains 1g ± 0,1g of fecal suspension corresponding to 0.5 to 0.8g of native stool. Capsules will be stored frozen at -80°C for up to 24 months pending use. The stability of biodiversity and viability of the frozen microbiota was regularly verified to ensure the efficacy of the transplantation (personal data).

Fecal microbiota Transplant (FMT)

Placebo capsules BIOLOGICAL

The "placebo" FMT capsules will be performed with the final dilution solution, ie the 80% glycerol solution used as a cryoprotectant. This solution will be double encapsulated like the FMT capsules.

Placebo of FMT

Eligibility Criteria

• Age: 18 Years - 105 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 18 years and \< 105 years
• Patient with at least one positive rectal swab for enterobacteria:
• extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenem-resistant Enterobacteriaceae (CRE), or who have had an ESBL-E or CRE infection within the year For ESBL-E carriers: an ESBL-E infection within the year is mandatory
• \- Patient able to take 50 capsules orally in a day and without swallowing disorders
• Healthy subjects ≥ 18 years and \< 50 years
• Body mass index \< 30 kg/m\^2
• Regular bowel movement defined as at least 1 stool every 2 daysand maximum than 3 stools per day

You may not qualify if:

• Current antibiotic treatment with te exception of long term antibiotic prophylaxis (duration of at least 3 months/year)
• Patients hospitalized in the intensive care unit
• Pregnancy or breastfeeding during the study
• Women of childbearing potential who are unwilling or unable to use an acceptable method of birth control \[such as oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (condoms)\] to avoid pregnancy for the entire study
• Patient under legal protection
• Participation in another interventional study
• Non-affiliation to a social security scheme
• Patient under AME
• Refusal to participate to the study
• Any history of or current proctologic disease or any acute condition, which in the investigator's judgment could harm the volunteer and/or compromise or limit the evaluation of the protocol or data analysis (for details, please see protocol)
• Subject under legal protection
• Participation in any other interventional study
• No-affiliation to a social security scheme
• Subject under AME
• Refusal to participate to the study

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (11)

Beaujon Hospital

Clichy, France

NOT YET RECRUITING

Henri Mondor Hospital

Créteil, France

NOT YET RECRUITING

Raymond Poincaré Hospital

Garche, France

NOT YET RECRUITING

Bicêtre Hospital

Le Kremlin-Bicêtre, France

NOT YET RECRUITING

Bichat Hospital

Paris, France

NOT YET RECRUITING

Bichat Hospital

Paris, France

RECRUITING

La Pitié Salpêtrière Hospital

Paris, France

NOT YET RECRUITING

Lariboisière Hospital

Paris, France

NOT YET RECRUITING

Saint Antoine Hospital

Paris, France

NOT YET RECRUITING

Saint Louis Hospital

Paris, France

NOT YET RECRUITING

Tenon Hospital

Paris, France

NOT YET RECRUITING

MeSH Terms

Conditions

Enterobacteriaceae Infections

Interventions

Fecal Microbiota Transplantation; Capsules

Condition Hierarchy (Ancestors)

Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Victoire De Lastours, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Victoire De Lastours, MD, PhD

CONTACT

+33 1 40 87 52 27; victoire.de-lastours@aphp.fr

Harry Sokol, MD, PhD

CONTACT

+33 1 49 28 24 73; harry.sokol@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blinded placebo-controlled randomized multicentric controlled trial with a 1:1 randomization.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-blinded placebo-controlled randomized multicentric controlled trial with a 1:1 randomization.

Study Record Dates

• First Submitted: July 31, 2021
• First Posted: September 5, 2021
• Study Start: January 11, 2024
• Primary Completion: May 1, 2026
• Study Completion (Estimated): April 1, 2028
• Last Updated: May 25, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (11)