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

Phase 2
Recruiting
Conditions
Resistance Bacterial
Interventions
Biological: Autologous FMT
Biological: Allogenic FMT
Registration Number
NCT04188743
Lead Sponsor
University Hospital, Ghent
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
150
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Autologous FMTAutologous FMTParticipants 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).
Allogenic FMTAllogenic FMTParticipants 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).
Primary Outcome Measures
NameTimeMethod
Number of participants with decolonization success/failure1 month after treatment

These participants were screened positive for MDRO's in stool cultures before treatment and monitored at least once per week up to 1 month after treatment. "Decolonization" = 3 consecutive negative cultures in minimal time span of 2 weeks.

Secondary Outcome Measures
NameTimeMethod
Side effectsup to 1 year after treatment

Monitor adverse events

Treatment effect on microbial community in participantsup to 1 year after treatment

Evaluation of gut bacterial composition changes in participants over time pre- and post-treatment with 16S ribosomal ribonucleic acid based metagenomic analysis.

Treatment tolerability1 month after treatment

The tolerability of the treatment is monitored with an in-house developed questionnaire considering the participant's opinion before, during and after the treatment on a score of 1 (very bad) to 5 (very good).

Trial Locations

Locations (1)

Ghent University Hospital

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Ghent, Oost-Vlaanderen, Belgium

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