Antimicrobial Resistant Organism Decolonization After Microbiome Perturbation

Microbial Colonization Clinical Trial

— ARO-DECAMP  

Official title:

Antimicrobial Resistant Organism Decolonization After Microbiome Perturbation (ARO-DECAMP): a Multi-centre, Randomized, Placebo-controlled Feasibility Pilot Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06214403
• Other study ID #: 23-5419
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 2024
• Est. completion date: July 2026

Study information

• Verified date: May 2024
• Source: University Health Network, Toronto
• Contact: Bryan Coburn, MD, PhD
• Phone: 416-634-7457
• Email: bryan.coburn[@]uhn.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: July 2026
• Est. primary completion date: January 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Antibiotic Resistant Infection
• Bacteremia
• Communicable Diseases
• Gram-negative Bacteremia
• Infections
• Microbial Colonization

Intervention

Drug:
• MET-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.
• Placebo
Microcrystalline Cellulose

Locations

Country	Name	City	State
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	Sinai Health	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	University Health Network	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse events	Frequency and grade	180 days
Other	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	180 days
Other	ARO colonization by culture at 30 and 90 days post-intervention	Defined as any positive result for ARO from any site	90 days
Other	Determine 90- and 180-day recurrence/re-infection rates (with the same organism) in each treatment arm		180 days
Other	AMR gene complement by sequencing at 30 and 90 days post-intervention		90 days
Other	90- and 180-day all-cause mortality		180 days
Other	ICU and hospital lengths of stay		180 days
Other	C. difficile carriage at days 30 and 90		90 days
Primary	Recruitment rate overall and by study site	Defined by the numbers of eligible, consented, and randomized patients	1.5 years
Primary	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
Secondary	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
Secondary	Number of biomarker samples collected, by sample type and timepoint	Successful adherence to biomarker sample collection is defined as >80% of participants having samples suitable for analysis at 30 days post-intervention	30 days
Secondary	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