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Study intervention not available. Manufacturer no longer producing MET-2.
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MET-2 | Experimental | 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). |
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| Placebo | Placebo Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MET-2 | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Recruitment rate overall and by study site | Defined by the numbers of eligible, consented, and randomized patients | 1.5 years |
| Adherence to MET-2/placebo for the treatment duration | 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 | 30 days |
| Measure | Description | Time Frame |
|---|---|---|
| Change in microbiome composition after intervention | Assessment of gut microbiome composition in pre- and post-randomization stool samples using bacterial culture and culture-independent (sequencing) assays. | 180 days |
| Number of biomarker samples collected, by sample type and timepoint |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse events | Frequency and grade | 180 days |
| 90- and 180-day infection rate | Infection will be defined as either isolation of a pathogenic species from any sterile site OR the initiation of a therapeutic course of antimicrobials with or without isolation of a pathogenic species from a sterile or non-sterile site |
Inclusion Criteria:
Adult (≥18 years old) inpatient not admitted to the ICU or equivalent (step-up and step-down units are eligible)
Positive blood culture with an ARO:
Currently receiving treatment for the bloodstream infection
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bryan Coburn, MD, PhD | University Health Network, Toronto | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Ottawa Hospital | Ottawa | Ontario | K1Y 4E9 | Canada | ||
| Sunnybrook Health Sciences Centre |
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| ID | Term |
|---|---|
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D016470 | Bacteremia |
| ID | Term |
|---|---|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001424 | Bacterial Infections |
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| Placebo | Drug | Microcrystalline Cellulose |
|
Successful adherence to biomarker sample collection is defined as >80% of participants having samples suitable for analysis at 30 days post-intervention |
| 30 days |
| Concentration of potential biomarkers in pre- and post-randomization blood and urine samples | 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). | 180 days |
| 180 days |
| ARO colonization by culture at 30 and 90 days post-intervention | Defined as any positive result for ARO from any site | 90 days |
| Determine 90- and 180-day recurrence/re-infection rates (with the same organism) in each treatment arm | 180 days |
| AMR gene complement by sequencing at 30 and 90 days post-intervention | 90 days |
| 90- and 180-day all-cause mortality | 180 days |
| ICU and hospital lengths of stay | 180 days |
| C. difficile carriage at days 30 and 90 | 90 days |
| Toronto |
| Ontario |
| M4N 3M5 |
| Canada |
| University Health Network | Toronto | Ontario | M5G 1L7 | Canada |
| Sinai Health | Toronto | Ontario | M6G 1X5 | Canada |
| D001423 | Bacterial Infections and Mycoses |
| D018805 | Sepsis |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |