Antimicrobial Resistant Organism Decolonization After Microbiome Perturbation (ARO-DECAMP)

University Health Network, Toronto

Status and phase: Not yet enrolling; Phase 2

Conditions: Gram-negative Bacteremia; Microbial Colonization; Antibiotic Resistant Infection

Treatments: Drug: MET-2; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT06214403

23-5419

Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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100 participants in 2 patient groups, including a placebo group

MET-2

Experimental group

Description:

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).

Treatment:

Drug: MET-2

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo