Antibiotic Resistant Infection, Gram-negative Bacteremia, Microbial Colonization
Conditions
Keywords
Microbial consortia, Microbiome, Decolonization, Infection, Bacteremia, Antibiotic, Microbiota, Antibiotic resistance
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.
Interventions
DRUGMET-2
Microbial Ecosystem Therapeutics (MET) is a defined microbial community derived from healthy donor stool. MET capsules are orally administered mixtures of pure cultures of human-derived bacterial strains.
DRUGPlacebo
Microcrystalline Cellulose
Sponsors
University Health Network, Toronto
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| 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). |
Countries
Canada
Contacts
PRINCIPAL_INVESTIGATORBryan Coburn, MD, PhD
University Health Network, Toronto
Outcome results
None listed