Clinical trial NCT06214403: Antimicrobial Resistant Organism Decolonization After Microbiome Perturbation
Official title: Antimicrobial Resistant Organism Decolonization After Microbiome Perturbation (ARO-DECAMP): a Multi-centre, Randomized, Placebo-controlled Feasibility Pilot Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Gram-negative Bacteremia
Microbial Colonization
Antibiotic Resistant Infection
Keywords: Microbial consortia
Microbiome
Decolonization
Infection
Bacteremia
Antibiotic
Microbiota
Antibiotic resistance
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2024-01-19
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Recruitment rate overall and by study site
timeFrame: 1.5 years
measure: Adherence to MET-2/placebo for the treatment duration
timeFrame: 30 days
Secondary outcomes:
measure: Change in microbiome composition after intervention
timeFrame: 180 days
measure: Number of biomarker samples collected, by sample type and timepoint
timeFrame: 30 days
measure: Concentration of potential biomarkers in pre- and post-randomization blood and urine samples
timeFrame: 180 days
Other outcomes:
measure: Adverse events
timeFrame: 180 days
measure: 90- and 180-day infection rate
timeFrame: 180 days
measure: ARO colonization by culture at 30 and 90 days post-intervention
timeFrame: 90 days
measure: Determine 90- and 180-day recurrence/re-infection rates (with the same organism) in each treatment arm
timeFrame: 180 days
measure: AMR gene complement by sequencing at 30 and 90 days post-intervention
timeFrame: 90 days
measure: 90- and 180-day all-cause mortality
timeFrame: 180 days
measure: ICU and hospital lengths of stay
timeFrame: 180 days
measure: C. difficile carriage at days 30 and 90
timeFrame: 90 days
Locations:
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Toronto
country: Canada
facility: Sinai Health
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Bryan Coburn, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: