Response to Emerging Antimicrobial Resistance With Containment Microbiota Therapy (REACT)

Phase 2

Not yet recruiting

• Conditions: Multi-Drug Resistant Organism Colonization
• Interventions: Drug: Allogeneic Microbiota in Glycerol (9%) (AMG)

• Registration Number: NCT06321536
• Lead Sponsor: Emory University

Brief Summary

REACT is a phase two, open-label, cluster randomized, crossover study of microbiota therapy (MT) to reduce colonization with multi-drug resistant organisms (MDRO). REACT is designed to assess the safety and efficacy of MT administered to subjects colonized with a MDRO. The overarching hypothesis is that MT can reduce MDRO colonization with safety that is comparable to observation.

Detailed Description

REACT is a phase two, open-label, cluster randomized, crossover study of microbiota therapy (MT) to reduce colonization with multi-drug resistant organisms (MDRO) in patients admitted to long-term care facilities. REACT is designed to test the safety and efficacy of instillation of donor intestinal microbiota.

Patients admitted to long-term care facilities (e.g. long-term acute care hospitals and ventilator-capable skilled nursing facilities) found to be MDRO colonized during prevalence screening activities performed in the related APPS study.

Facilities undergo prevalence sampling that involves participant peri-rectal, inguinal, and stool sampling to estimate the prevalence of targeted MDROs (CRE, ESBL, VRE, MDRP, C. difficile) under the accompanying APPS protocol. Patients who are positive with at least one targeted MDRO are eligible for an Emory manufactured MT product (via rectal enema or feeding tube), or observation followed by repeat sampling at Days 7, 14, 21, and 28. A repeat prevalence sample will then be conducted at all facilities. After a washout period, facilities then undergo another prevalence sample, crossover to the opposite assignment for recruiting patients (i.e. Observation -\> MT or MT -\> Observation) followed by another facility prevalence sample. Participants will be followed with collection of data on adverse events/safety/changes in medications at Days 0, 7, 14, 21, 28, and followed up once a month for 6 months, after MT administration.

Study Timeline

• Study First Submitted: 2024-03-13
• Study First Submitted QC: 2024-03-13
• Study First Posted: 2024-03-20
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-14
• Last Update Posted: 2024-11-18
• Study Start: 2025-01
• Primary Completion: 2025-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

1. Be able (or have available a Legal Authorized Representative who is able) to understand and sign a written informed consent document.
2. Be at least 18 years old at the time of consent.
3. Be able to comply with all study protocol requirements, including able to receive MT as retention enema or via enteral feeding tube and be available for the duration of the study follow up.
4. Be colonized with a target MDRO (CRE, VRE, ESBL, MDR Pseudomonas, and/or toxigenic C. difficile) as detected by bacterial culture of stool or peri-rectal swab (collected in companion APPS facility prevalence sampling protocol).
5. Be able to discontinue or complete planned courses of antibiotics, probiotics, and other microbiota restoration therapies by Day -1 and not resume until after Day 28.
6. The effects of the MT on the developing human fetus are unknown. For this reason, persons of child-bearing potential (POCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
7. Agree to refrain from receptive anal intercourse until the last biological specimen (stool sample or peri-rectal swab) is collected (Day 28).

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Exclusion Criteria

1. Are pregnant, breastfeeding, lactating, or planning a pregnancy during study duration (through 4 weeks after the last dose of investigational product, or MT), if POCBP.

2. Have known uncontrolled intercurrent illness(es):

   1. Symptomatic congestive heart failure
   2. Acute coronary syndrome
   3. Cardiac arrhythmia
   4. Untreated in-situ colorectal cancer
   5. Toxic megacolon
   6. Ileus
   7. Positive stool studies without completion of treatment course (including ova and parasites, Salmonella spp, Shigella, Campylobacter, and other enteropathogens).
   8. other acute illness that in the opinion of the investigator could affect the safety of the participant or make study data uninterpretable.

3. Are on systemic antibiotics for any reason other than treatment of recent MDRO infection or clear anticipated need for antibiotics during the follow up period that cannot be rescheduled (e.g. fluoroquinolone prophylaxis for percutaneous nephrostomy tube exchange, prolonged antibiotic course for endocarditis). Participants must complete the planned antibiotic course by study Day -1.

4. Have a compromised immune system, defined as:

   1. AIDS with CD4+ T-cell count <200 and detectable HIV viral load on most recent assay.
   2. Absolute neutrophil count (ANC) <1,000 neutrophils / mL on day of enrollment.
   3. Active malignancy requiring intensive induction chemotherapy, radiotherapy, or biologic treatment within 2 months prior to enrollment.
   4. History of hematopoietic cell transplantation, either allogeneic or autologous in the last 1 year.

5. Have a history of significant food allergy that led to anaphylaxis or hospitalization.

6. Have a life expectancy of 24 weeks or less

7. Have any condition that, in the opinion of the investigator, might interfere with study objectives or limit compliance with study requirements, including but not limited to:

   1. Known active intravenous drug or alcohol abuse
   2. Uncontrolled psychiatric illness
   3. Social situations (e.g. incarceration)

8. Received an interventional agent (drug, device, or procedure) within 28 days prior to enrollment.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Group 1: MT then Observation	Allogeneic Microbiota in Glycerol (9%) (AMG)	Group 1 will offer Microbiome therapeutic (MT) to all MDRO-positive patients (i.e., intervention condition) during facility study period 1, followed by a wash-out period, during which several patients are expected to be discharged and new patients are expected to be admitted. In facility study period 2, all consenting MDRO-positive patients (i.e. control condition) will observed with weekly sampling during study period 2.
Group 2: Obervation then MT	Allogeneic Microbiota in Glycerol (9%) (AMG)	Group 2 will reverse the order of the intervention and control conditions relative to Group 1 (i.e., will conduct observation during facility study period 1, have a wash-out period, and then will offer MT to all MDRO-positive patients during facility study period 2).

Primary Outcome Measures

Name	Time	Method
Difference in severity of unsolicited AEs	Day 0 and Day 28	Difference in severity of unsolicited AEs will be collected between Day 0 and Day 28. Graded as mild, moderate or severe and compared in AMG-treated vs Observation participants
Difference in number of solicited Adverse Events (AEs)	Day 0, Day 7 post-intervention	Difference in number of solicited AEs between Day 0 and Day 7 in AMG-treated vs Observation participants.
Difference in severity of solicited AEs	Day 0, Day 7 post-intervention	Difference in severity of solicited AEs will be compared in AMG-treated vs Observation participants. Graded as mild, moderate or severe, up to 7 days post-intervention.
Difference in number of unsolicited AEs	Day 0, Day 28 post-intervention	Difference in number of unsolicited AEs between Day 0 and Day 28 in AMG-treated vs Observation participants.
Difference in proportion of participant stool positive cultures for any target MDRO among AMG-treated compared to Observation participants	Day 28 post-intervention	Difference in proportion of participant stool cultures at Day 28 positive will be measured for any target MDRO among AMG-treated compared to Observation participants

Secondary Outcome Measures

Name	Time	Method
Proportion of stool cultures at Day 28 positive for category-specific MDROs	Day 28	Proportion of stool cultures at Day 28 positive for category-specific MDROs (e.g. ESBL, CRE, MDRP, VRE).
Count of AEs of Special Interest (AESIs)	Day 180	Count of AEs of Special Interest (AESIs) at day Day 180, censored by last telephone visit or death, whichever is later.
Count of serious AEs (SAEs)	Day 180	Count of serious AEs (SAEs) between Day 0 and Month 6 (Day 180) censored by last telephone visits or death, whichever is later.

Trial Locations

Locations (1)

Emory University Hospital; 🇺🇸 Atlanta, Georgia, United States