Further MT for AntIbiotic-Resistant Bacterial Colonization in Inpatients (FAIR)

• ClinicalTrials.gov Identifier: NCT05835206
• Recruitment Status: Not yet recruiting
• First Posted: April 28, 2023
• Last Update Posted: September 21, 2023
• Sponsor: Emory University
• Collaborator: Centers for Disease Control and Prevention
• Information provided by (Responsible Party): Michael Woodworth, Emory University

Tracking Information

• First Submitted Date: April 18, 2023
• First Posted Date: April 28, 2023
• Last Update Posted Date: September 21, 2023
• Estimated Study Start Date: October 2023
• Estimated Primary Completion Date: June 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 29, 2023)

• Change in the MDRO colony-forming unit (CFU) densities [ Time Frame: Day 0, day 14, and 24 weeks ]
  MDRO colony-forming unit (CFU) densities from quantitative stool cultures in placebo vs IP-treated participants.
• Change in proportion of participants MDRO colonized after the investigational product (IP) [ Time Frame: Day 0, day 14, and 24 weeks ]
  Proportion of stool cultures positive for any target MDRO will be compared in IP-treated vs placebo-treated participants.

Original Primary Outcome Measures (submitted: April 18, 2023)

• Change in the MDRO colony-forming unit (CFU) densities [ Time Frame: Day 0, day 14, and 24 weeks ]
  MDRO colony-forming unit (CFU) densities from quantitative stool cultures in placebo vs IP-treated participants.
• Change in the efficacy of the investigational product (IP) for MDRO decolonization [ Time Frame: Day 0, day 14, and 24 weeks ]
  Proportion of stool cultures positive for any target MDRO

Current Secondary Outcome Measures (submitted: April 18, 2023)

• Estimate safety of the of the IP for MDRO colonization after infection [ Time Frame: Day 0, 24 weeks ]
  The frequency of adverse events from IP efficacy for reducing recurrent MDRO infection will be assessed by the frequency of MDRO infections at 24 weeks
• Severity of adverse events caused by administration of the investigational product [ Time Frame: Day 0, 24 weeks ]
  Severity of adverse events after administration of MT will be graded as mild, moderate or severe, form the time of MT administration up to 24 weeks.
• Estimate efficacy of the IP for reducing recurrent MDRO infection [ Time Frame: Day 0, 24 weeks ]
  Efficacy will be measured by the frequency of MDRO infections from Day 0 of the first cycle until 24 weeks
• Time to recurrent MDRO infection after IP administration [ Time Frame: Day 0, 24 weeks ]
  Time to recurrent MDRO infection from Day 0 of first cycle censored at last final safety visit, or death.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Further MT for AntIbiotic-Resistant Bacterial Colonization in Inpatients
• Official Title: A Randomized Controlled Trial to Further Microbiota Therapy for AntIbiotic-Resistant Bacterial Colonization in Inpatients.

Brief Summary

The purpose of this study is to better understand the effectiveness and safety of microbiome therapies (MT) as a treatment for patients with Multidrug Resistant Organism (MDRO) colonization after an infection. Limited data from prior studies suggest that MT may be an effective treatment to reduce intestinal MDRO colonization Although shedding of MDROs from patients to their surrounding environment is a recognized pathway of transmission, the potential effect of MT on the transmission of MDRO to other patients in the hospital environment is unclear. This study will test the safety and efficacy of MT for this use in hospitalized patients. This study will also help design larger studies.

The MT may help reduce MDROs that colonize the gut. By reducing colonization before infections happen, this could help doctors avoid using "last resort" antibiotics that can have serious side effects like kidney damage. The reduction in MDROs after MT was originally identified in patients treated with MT for recurrent Clostridioides difficile (often called "C. diff") diarrhea. It has been shown that a type of MT called fecal microbiota transplant (FMT) can eliminate both C. difficile and other resistant bacteria.

Detailed Description

Antimicrobial resistance (AR) has been declared by the World Health Organization to be one of the greatest threats to global health. Every year, at least 2 million people are infected with antibiotic-resistant bacteria, and over 23,000 dies from such infections.

This study aims to take initial steps to directly address these public health priorities and clinical threats of MDRO by estimating the safety of the IP in reducing patient-level intestinal MDRO colonization as well as the effect of the IP on environmental contamination. FAIR is a phase 2, randomized, placebo-controlled, double-blind, parallel, clinical trial of the IP for the treatment of MDRO colonization.

The hypothesis is that lyophilized human intestinal microbiota will safely and efficaciously reduce MDRO colonization. This is a randomized, controlled, clinical trial with two arms: a placebo arm and an intervention arm. The target population will include 40 adult inpatients with the colonization of a multi-drug resistant organism (MDRO) after infection. Target MDRO colonization is defined as a positive clinical microbiology bacterial culture and antibiotic susceptibility result that includes one or more of the following: carbapenem-resistant Enterobacteriaceae (CRE), vancomycin-resistant Enterococcus spp (VRE), extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae, multidrug-resistant (MDR) Acinetobacter and/or MDR Pseudomonas

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Multi-drug Resistant Organism

Intervention

• Drug: Microbiome Therapeutic
  Participants will receive a single course of study treatment (IP, Encapsulated Microbiota): Orally delivered, non-frozen, encapsulated investigational intestinal microbiota, consisting of 16 capsules. One dose (8 capsules) is administered daily (QD) for 2 days. The capsules are to be taken orally with water on an empty stomach.
  Other Name: Intervention Group
• Drug: Placebo
  Participants will receive a single course of study treatment (Color-matched placebo capsules containing microcrystalline cellulose (MCC) powder), consisting of 16 capsules. One dose (8 capsules) is administered daily (QD) for 2 days. The capsules are to be taken orally with water on an empty stomach.
  Other Name: Control Group

Study Arms

• Experimental: microbiome therapeutic
  The study intervention is manufactured from a healthy screened donor as an investigational product (IP) and delivered via swallowed capsule after room reset of the patient's hospital room.
  Intervention: Drug: Microbiome Therapeutic
• Placebo Comparator: Placebo
  The control arm will remain in routine contact precautions per standard of care, take placebo capsules, and have a room reset.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: April 18, 2023): 40
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2025
• Estimated Primary Completion Date: June 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Be able to (or have an available Legal Authorized Representative who is able to) understand and be willing to sign a written informed consent document.
• Be at least 18 years old at the time of consent.
• Be able and willing to comply with all study protocol requirements, including the ability to swallow capsules.
• Be colonized with a target MDRO (CRE, VRE, ESBL, MDR Acinetobacter, and/or MDR Pseudomonas) as detected by bacterial culture of stool or perianal/rectal swab.
• Be willing to discontinue antibiotics, probiotics, or other microbiota restoration therapies, and proton pump inhibitors (PPIs) at least one day prior to study Day 0 and throughout the study.
• The effects of the IP on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) 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.
• If the potential participant is male, and the partner is of childbearing potential, the subject agrees to practice at least one effective method of birth control for the duration of the study.

Exclusion Criteria:

• Be pregnant, breastfeeding, lactating, or planning a pregnancy during the study duration (through 4 weeks after the last dose of investigational product, or IP), if women of childbearing potential (WOCBP).
• Have known uncontrolled intercurrent illness(es) such as, but not limited to: Symptomatic congestive heart failure, acute coronary syndrome, cardiac arrhythmia, untreated in situ colorectal cancer, toxic megacolon or ileus, use of medications that decrease GI motility and increase broncho-aspiration risk (e.g. loperamide, diphenoxylate/atropine, cholestyramine), or history of positive stool studies or cultures in the last 30 days for ova, parasites, Salmonella, Shigella, Campylobacter, or other enteropathogens other than those detected by screening MDRO stool cultures for inclusion.
• Have any other intercurrent acute illness that in the opinion of the investigator will preclude the subject from entering the study.
• Be on systemic antibiotics for any reason other than if the MDRO infection was recent or the potential participant is still taking antibiotics for target MDRO at the time of screening. If the latter, then the participant must complete the planned antibiotic course by study Day -1.
• Inability to discontinue PPI therapy.
• Have a compromised immune system, defined as AIDS with a cluster of differentiation 4 (CD4)+ T-cell count <200, Absolute neutrophil count (ANC) <1,000 neutrophils / mL on the day of enrollment, active malignancy requiring intensive induction chemotherapy, radiotherapy, or biologic treatment within 2 months of enrollment or history of hematopoietic cell transplantation, either allogeneic or autologous in the last 1 year.
• Have a history of significant food allergy that led to anaphylaxis or hospitalization.
• Have a life expectancy of 24 weeks or less
• 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: Known active intravenous drug or alcohol abuse, psychiatric illness, and/or social situation
• Participated in an investigational study that also meets one of the following criteria: Received an interventional agent (drug, device, or procedure) in the last 28 days or enrollment in any other interventional study for MDROs.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Michael Woodworth, MD, MSc; 404-778-1691; mwoodwo@emory.edu

Contact: Amanda Strudwick, RN; 404-727-9193; astrudw@emory.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05835206
• Other Study ID Numbers: STUDY00003613; 1U54CK000601-01 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: The researchers will share all deidentified data included in the publication without restriction.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: At the time of publication
• Access Criteria: Data will be uploaded to relevant repositories (e.g. National Center for Biotechnology Information (NCBI), Sequence Read Archive (SRA) for sequencing data and Dataverse or similar for clinical trial data)

• Current Responsible Party: Michael Woodworth, Emory University
• Original Responsible Party: Same as current
• Current Study Sponsor: Emory University
• Original Study Sponsor: Same as current
• Collaborators: Centers for Disease Control and Prevention

Investigators

• Principal Investigator: Michael Woodworth, MD, MSc; Emory University

• PRS Account: Emory University
• Verification Date: September 2023