Antimicrobial Resistant Organism Decolonization After Microbiome Perturbation

Phase 2

Not yet recruiting

• Conditions: Gram-negative Bacteremia; Antibiotic Resistant Infection; Microbial Colonization
• Interventions: Drug: MET-2; Drug: Placebo

• Registration Number: NCT06214403
• Lead Sponsor: University Health Network, Toronto

Brief Summary

ARO-DECAMP is a multi-centre, placebo-controlled, pilot and feasibility randomized controlled trial for the microbial consortium Microbial Ecosystem Therapeutic-2. Non-intensive care unit patients ≥ 18 years old diagnosed with a bloodstream infection and receiving treatment for an antibiotic resistant organism will be included. Participants will be randomized to receive either MET-2 or placebo for 10 days. Recruitment rate and study intervention adherence will be evaluated for feasibility. Participants will be followed for 180 days, and biological samples will be collected periodically for clinical, ecological, and biomarker outcomes.

Detailed Description

Reconstituting the perturbed microbiome is a novel therapeutic modality with the potential to decrease ARO colonization and infection and combat AMR without additional pressure for selection of further antimicrobial resistance. No trial has yet assessed the potential of a therapeutic microbial consortium for ARO decolonization and infection prevention after antibiotic treatment.

The investigational product, Microbial Ecosystem Therapeutic-2 (MET-2), is a defined microbial community derived from healthy donor stool. MET capsules are orally administered mixtures of bacterial strains cultured from the stool of a healthy donor. This study is designed to determine if a trial of administration of MET-2 after antibiotic treatment for bloodstream infections is feasible. Stool and plasma biomarkers to assess the effects of the intervention will also be evaluated.

Study Timeline

• Study First Submitted: 2023-12-21
• Study First Submitted QC: 2024-01-09
• Study First Posted: 2024-01-19
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-03
• Last Update Posted: 2024-12-04
• Study Start: 2025-07
• Primary Completion: 2027-01
• Study Completion: 2027-07

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. Adult (≥18 years old) inpatient not admitted to the ICU or equivalent (step-up and step-down units are eligible)

2. Positive blood culture with an ARO:

   • AmpC beta-lactamase producing species: Enterobacter cloacae, Citrobacter spp., Klebsiella aerogenes, Serratia spp., Morganella morganii, Hafnia alvei OR
   • ESBL-producing gram-negative bacilli

3. Currently receiving treatment for the bloodstream infection

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Exclusion Criteria

1. Inability to swallow oral MET-2 or placebo capsule
2. Recipient of small bowel transplant
3. Inflammatory bowel disease, short bowel syndrome, diverting/non-diverting ileo/colostomy
4. Use of >3 days over-the-counter or prescription probiotics (not including food additives) within 10 days of enrolment
5. Receipt of fecal microbiota transplant (FMT) within 3 months of enrolment
6. Absolute neutrophil count <0.5x109/L
7. Death expected within 72 hours of enrolment
8. Planned continuation of non-prophylaxis antimicrobial therapy active against the bloodstream isolate for >42 days
9. Known pregnancy, planning to become pregnant during the study period, or breastfeeding
10. Any other reason in view of the site investigator or treating team

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MET-2	MET-2	Participants randomized to the intervention will receive MET-2 daily for 10 days. MET-2 capsules are administered orally at 0.5 g per capsule, containing 3.1 x 10\^5-10\^11 colony forming units (CFU). An initial loading dose of 10 MET-2 capsules/day will be taken for 2 days (5 grams total). For the following 8 days, participants will take a maintenance dose of 3 MET-2 capsules/day (1.5 grams total).
Placebo	Placebo	Participants randomized to the placebo will receive microcrystalline cellulose in a capsule, identical in appearance to MET-2 but not containing live bacteria. Participants will take the placebo in the same dosing schedule as the MET-2 arm: 10 capsules daily for 2 days, followed by 3 capsules daily for 8 days.

Primary Outcome Measures

Name	Time	Method
Recruitment rate overall and by study site	1.5 years	Defined by the numbers of eligible, consented, and randomized patients
Adherence to MET-2/placebo for the treatment duration	30 days	Defined as \>80% of loading dose (16/20 pills) + \>75% of daily doses (18/24 pills) for the maintenance period, as determined by returned unused capsules

Secondary Outcome Measures

Name	Time	Method
Concentration of potential biomarkers in pre- and post-randomization blood and urine samples	180 days	Microbial-derived metabolites (short chain fatty acids and bile acids in blood, and 3-indoxyl sulfate in urine), markers of intestinal permeability (soluble CD14, LPS, LPS-binding protein, ZO-1, intestinal fatty acid protein), immune cell profiles (CD8 T lymphocytes, CD4 T lymphocytes, T regulatory cells, B lymphocytes, Th17 cells, Th1 cells).
Number of biomarker samples collected, by sample type and timepoint	30 days	Successful adherence to biomarker sample collection is defined as \>80% of participants having samples suitable for analysis at 30 days post-intervention
Change in microbiome composition after intervention	180 days	Assessment of gut microbiome composition in pre- and post-randomization stool samples using bacterial culture and culture-independent (sequencing) assays.

Trial Locations

Locations (4)

University Health Network; 🇨🇦 Toronto, Ontario, Canada

The Ottawa Hospital; 🇨🇦 Ottawa, Ontario, Canada

Sunnybrook Health Sciences Centre; 🇨🇦 Toronto, Ontario, Canada

Sinai Health; 🇨🇦 Toronto, Ontario, Canada