Clinical trial NCT05835206: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Multi-drug Resistant Organism
Keywords: Carbapenem-resistant Enterobacteriaceae (CRE)
Vancomycin-Resistant Enterococcus (VRE)
Extended Spectrum Beta-Lactamase (ESBL)
Multi-Drug Resistant (MDR) Acinetobacter
Multi-Drug Resistant (MDR) Pseudomonas
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Centers for Disease Control and Prevention
First posted: 2023-04-28
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 die 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 multi-drug resistant organisms (MDRO) colonization after infection. Target MDRO colonization is defined as a positive clinical microbiology bacterial culture and antibiotic susceptibility result that is consistent with 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

Eligibility criteria: Inclusion Criteria:

* Be able to (or have an available Legally 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 able and willing to discontinue systemic antibiotics at least one day prior to study Day 0 and for as long as medically able to do so throughout the study.
* Be willing to discontinue probiotics or other microbiota restoration therapies at least one day prior to study Day 0 and for the duration of study participation.
* 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.

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, the participant must be able (in the opinion of their treating providers) to complete the planned antibiotic course by study Day -1.
* Have a compromised immune system, defined as AIDS with a cluster of differentiation 4 (CD4)+ T-cell count \<200, history of documented absolute neutrophil count (ANC) \<1,000 neutrophils/mL within 14 days of D0, 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.

Primary outcomes:
measure: Change in stool MDRO colony-forming unit (CFU) density
timeFrame: Day 0, day 14 of last cycle (each cycle is 14 days), and 28 weeks
measure: Change in proportion of MDRO colonized participants after last treatment cycle with the investigational product (IP)
timeFrame: Day 0, day 14 of last cycle (each cycle is 14 days), and 28 weeks
Secondary outcomes:
measure: Estimate safety of the IP for MDRO colonization after infection
timeFrame: Day 0, day 7, day 14 of last cycle (each cycle is 14 days), and 28 weeks
measure: Severity of adverse events caused by administration of the investigational product
timeFrame: Day 0, day 7, day 14 of last cycle (each cycle is 14 days), and 28 weeks
measure: Estimate efficacy of the IP for reducing recurrent MDRO infection
timeFrame: Day 0, 24 weeks post Day 14 of last cycle (each cycle is 14 days)
measure: Time to recurrent MDRO infection after IP administration
timeFrame: Day 0, 24 weeks post Day 14 of last cycle (each cycle is 14 days)
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory Rehabilitation Hospital
state: Georgia
city: Atlanta
country: United States
facility: Emory University Clinical Research Network
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital (EUH)
state: Georgia
city: Atlanta
country: United States
facility: Emory University at Wesley Woods Hospital
state: Georgia
Study officials:
affiliation: Emory University
name: Michael Woodworth, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: