Decolonization of Gram-negative Multi-resistant Organisms (MDRO) with Donor Microbiota (FMT)

NCT ID: NCT04188743

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-18
• Study Completion Date: 2025-12-30

Brief Summary

Colonization by Multiple Drug Resistant Organisms (MDROs) during patient hospitalization requires expensive isolation measures and renders the return or transfer to other departments or institutions often impossible. Currently there is no specific treatment available. Patients have to wait for spontaneous clearance which can take months or does not happen at all.

The study will test the effect of Fecal Microbiota Transfer (FMT) on gut MDRO colonization. The focus will be on patients with a long-term colonization by Gram-negative bacteria for which isolation is warranted. Participants will be randomized into two treatment groups; allogenic FMT versus autologous FMT. A third group of participants will be monitored but will not receive an FMT. Decolonization rate will be compared one month after treatment. Additionally gut microbial composition will be studied up to one year after FMT.

Detailed Description

This double-blind controlled randomized study will test the efficacy of Fecal Microbiota Transfer (FMT) on gut Multiple Drug Resistant Organism (MDRO) colonization.

Participants:

The study targets hospitalized patients (>18 years old) that need to stay in isolation because of colonization by Carbapenem-resistant Enterobacteriales (CRE), non-E. coli Enterobacteriales that produce extended spectrum beta-lactamase (ESBL) or Multi Drug Resistant (MDR) Pseudomonas and MDR Acinetobacter species. Participants will be randomized in two groups (allogenic and autologous FMT). Additionally a third group of participants will be monitored without intervention.

Treatment:

Participants in the allogenic FMT- group will receive treatment using healthy donor microbiota preferably through naso-duodenal/-jejunal administration (Cortrak). Donor material will be supplied by the Ghent Stool Bank. The colonization status will be monitored on a regular basis (at least once per week) by culturing fecal swabs. Additionally fecal samples will be taken on fixed time points for microbial composition analysis (16S ribosomal ribonucleic acid metagenomics).

Controls:

Participants in the autologous FMT-group will will receive an FMT with their own microbiota to account for the effects of the intervention itself. Participants in the "no intervention" group will not receive an FMT. Both control groups will be monitored and sampled identically to the allogenic FMT-group.

Outcome:

The primary outcome (MDRO-decolonization rate in treatment versus control) will be evaluated 1 month after FMT. Secondarily, safety and tolerability of the treatment will be assessed. The patients will be monitored up to 1 year after treatment to evaluate microbiome composition and to define parameters in the microbiome that are associated with clinical outcome.

Conditions

Resistance Bacterial

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Allogenic FMT

Participants in the allogenic FMT- group will receive FMT-treatment using healthy donor microbiota supplied by the Ghent Stool Bank. The donor stool (50g) is processed shortly after production and tested intensively. It's frozen at -80°C until administration via naso-duodenal/-jejunal tube (Cortrak).

Group Type: EXPERIMENTAL

Allogenic FMT

Intervention Type: BIOLOGICAL

Transplantation of fecal microbiota from a donor into a recipient

Autologous FMT

Participants in the autologous FMT- group will receive FMT-treatment using their own microbiota to account for effects due to the treatment itself. Their stool is processed as close to the treatment as feasible. It's processed and frozen at -80°C until administration via naso-duodenal/-jejunal tube (Cortrak).

Group Type: PLACEBO_COMPARATOR

Autologous FMT

Intervention Type: BIOLOGICAL

Transplantation of autologous fecal microbiota

No intervention

Participants in the "No intervention"-group will not receive any treatment but will be monitored similarly as the "Allogenic FMT" and "Autologous FMT" groups.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Allogenic FMT

Transplantation of fecal microbiota from a donor into a recipient

Intervention Type: BIOLOGICAL

Autologous FMT

Transplantation of autologous fecal microbiota

Intervention Type: BIOLOGICAL

Other Intervention Names

Fecal Microbiota Transplantation with donor stool; Fecal Microbiota Transfer with donor stool; Fecal Microbiota Transplantation with own stool; Fecal Microbiota Transfer with own stool

Eligibility Criteria

Inclusion Criteria

• Participants must be at least 18 years of age, and must sign the 'informed consent' form and thus agree with the data collection, sampling and FMT.
• At least 2 consecutive confirmations of MDRO colonization in faeces, which complicate the necessary follow-up and/or therapy for the patient.
• Participants must be able to endure the treatment (evaluated by treating physician).

Exclusion Criteria

• Inflammatory bowel disease (Crohn's disease, ulcerative colitis ...)
• Diagnosed hereditary blood disease (Haemophilia, Von Willebrand ...)
• Chronic liver disease
• Active drug use or alcohol abuse / dependence, which according to the researchers' opinion may interfere with the patient's participation in the study
• Simultaneous use of probiotics (except yoghurt)
• Existing immune deficiency (congenital or acquired), or concomitant immunomodulatory treatment (including systemic corticosteroids) in the 12 weeks prior to randomization, nasal or inhaled corticosteroid use is permitted
• Positive pregnancy test (or potentially pregnant)
• Breastfeeding
• Severe food allergy (anaphylaxis, urticarial)
• Antibiotic treatment up to 7 days before FMT, or planned to start within one month after FMT.

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

Sponsors

Research Foundation Flanders

OTHER

Sponsor Role: collaborator

University Hospital, Ghent

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bruno Verhasselt, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Ghent

Locations

Ghent University Hospital

Ghent, Oost-Vlaanderen, Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Bruno Verhasselt, Prof. Dr.

Role: CONTACT

bruno.verhasselt@uzgent.be

+3293322226

Hannelore Hamerlinck, Master

Role: CONTACT

hannelore.hamerlinck@uzgent.be

+3293323637

Facility Contacts

Bruno Verhasselt

Role: primary

bruno.verhasselt@uzgent.be

Other Identifiers

2018/0966

Identifier Type: OTHER

Identifier Source: secondary_id

BC-3034

Identifier Type: -

Identifier Source: org_study_id