Using microbiota therapy to combat drug-resistant infections

Response to Emerging Antimicrobial Resistance With Containment Microbiota Therapy

This study is testing whether giving patients in long-term care facilities a special treatment using healthy gut bacteria can help them get rid of drug-resistant infections.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Emory University (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 4 sites (Atlanta, Georgia and 3 other locations)
• Trial ID: NCT06321536 on ClinicalTrials.gov

What this trial studies

REACT is a phase two, open-label, randomized, controlled trial that investigates the use of microbiota therapy (MT) to reduce colonization of multi-drug resistant organisms (MDRO) in patients residing in long-term care facilities. The study aims to assess the safety and efficacy of administering donor intestinal microbiota through rectal enema or feeding tube to patients identified as MDRO colonized. Participants will be monitored for adverse events and changes in medication over a period of 28 days, with follow-up extending for six months post-treatment. The overarching hypothesis is that MT can effectively reduce MDRO colonization with a safety profile comparable to observation.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older who are colonized with targeted multi-drug resistant organisms and are admitted to long-term care facilities.

Not a fit: Patients who are not colonized with multi-drug resistant organisms or those unable to comply with study protocols may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could significantly reduce the prevalence of multi-drug resistant infections in vulnerable populations, improving patient outcomes.

How similar studies have performed: Other studies have shown promise in using microbiota therapy for various conditions, suggesting potential for success in this novel application against multi-drug resistant organisms.

Eligibility criteria

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) 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).

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.

Where this trial is running

Atlanta, Georgia and 3 other locations

• A.G Rhodes Wesley Woods — Atlanta, Georgia, United States (Recruiting)
• Emory Long Term Acute Care (LTAC) — Decatur, Georgia, United States (Recruiting)
• RML Specialty Hospital — Hinsdale, Illinois, United States (Recruiting)
• Penn Medicine Rittenhouse — Philadelphia, Pennsylvania, United States (Recruiting)

Study contacts

• Principal investigator: Michael Woodworth, MD — Emory University
• Study coordinator: Deepti Suchindran, PhD

Conditions Multi-Drug Resistant Organism Colonization; Multi-Drug Resistant Organism; Fecal Microbiota Transplant; Antibiotic Resistance; Long-Term Care Facilities