Comparison of Three Interventions for Antibiotic-Resistant Bacteria (ARB) Decolonization From the Gastrointestinal Tract

NCT07094984 | Recruiting

• 2 other identifiers: STOP-ARB32022/ABM/03/00044/P/07
• Study Type: interventional
• Target: 360
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this research experiment is to evaluate the effectiveness of fecal microbiota transplantation (FMT) preceded by antibiotic pre-treatment versus probiotic therapy and a standard-of-care equivalent diet designed to stimulate the growth of eubiotic gut microbiota (an active comparator enhancing the ethical value of the study and increasing the chances of spontaneous decolonization of antibiotic-resistant bacteria (ARB) in the absence of any active intervention recommended by Scientific Societies) in the decolonization of bacteria with the most clinically significant antibiotic resistance mechanisms from the gastrointestinal tract of colonized patients. This study addresses the urgent need highlighted by the World Health Organization (WHO) for new strategies to combat antibiotic resistance, aiming to prevent its progression into a global pandemic that could undermine the achievements of modern civilization. Study Hypotheses:

• The decolonization rate of ARB bacteria in patients undergoing the intervention (FMT or probiotic therapy) is the same as in patients treated with standard-of-care (SoC) alone.
• The decolonization rate of ARB bacteria in the intervention groups (FMT or probiotic therapy) is at least 20 percentage points higher than in patients treated with the standard approach (diet). The findings from this study may contribute to developing innovative microbiota-based therapies for the decolonization of antibiotic-resistant bacteria and help reduce the global burden of antibiotic resistance.

Conditions

Drug Resistance, Bacterial; Antimicrobial Drug Resistance

Keywords

Fecal Microbiota Transplantation; FMT; Antibiotic-resistant bacteria decolonization; Eradication procedure; probiotic therapy; eubiotic diet

Outcome Measures

Primary Outcomes (1)

• Complete decolonization of gastrointestinal antibiotic-resistant bacteria (ARB)

  Proportion of participants achieving complete decolonization of ARB from the gastrointestinal tract, defined as at least two consecutive negative rectal swab cultures (or stool cultures), taken at least one day apart, at day 60 following completion of the eradication procedure. Bacterial resistance mechanisms include ESBL, CRE, VRE, and MRSA. If available, PCR confirmation of absence of resistance genes is required for final classification as eradicated.

  60 days after completion of assigned intervention

Secondary Outcomes (1)

• Complete decolonization of ARB at days 30, 90, and 180

  30, 90, and 180 days post-intervention

Study Arms (3)

Fecal Microbiota Transplantation (FMT) group

EXPERIMENTAL

Participants in the Fecal Microbiota Transplantation (FMT) arm receive antibiotic pre-treatment for five days (days 1-5), followed by bowel cleansing on day 6. FMT is then administered either orally in capsule form on day 7 (full dose) and continued with a prolonged capsule intake regimen from days 9 to 14, or via colonoscopy on days 7 and 14 if capsules cannot be taken. The FMT material is provided by the Human Biome Institute and aims to restore a healthy gut microbiota to facilitate decolonization of antibiotic-resistant bacteria. Patients in this arm are hospitalized during the treatment phase for close monitoring.

Other: Fecal microbiota transplantation (FMT)

Probiotic therapy group

EXPERIMENTAL

Participants in the probiotic therapy arm receive bowel cleansing on day 6, followed by oral administration of a multistrain probiotic preparation from days 7 to 26. The probiotic contains 8 bacterial strains, including 4 Lactobacillus, 3 Bifidobacterium, and 1 Streptococcus strain, with a total daily dose of 450 billion live lyophilized bacteria (administered twice daily). The goal is to support gut microbiota modulation and promote decolonization of antibiotic-resistant bacteria. Treatment and monitoring are conducted on an outpatient basis.

Dietary Supplement: Probiotic Therapy

Eubiotic gut microbiota boosting diet group

EXPERIMENTAL

Participants in the diet arm receive a scientifically formulated, eubiotic gut microbiota boosting diet aimed at promoting the natural restoration of healthy intestinal flora and supporting spontaneous decolonization of antibiotic-resistant bacteria. The dietary intervention begins after bowel cleansing on day 6 and continues daily for 38 days. Meals are prepared and delivered by a specialized catering service according to a standardized nutritional plan developed by clinical dietitians. The intervention is conducted in an outpatient setting, with patients receiving instructions, materials, and monitoring tools at treatment initiation

Other: Gut Microbiota Boosting Diet

Interventions

Fecal microbiota transplantation (FMT) OTHER

FMT administered after antibiotic pre-treatment and bowel cleansing. Delivered either in capsule form or via colonoscopy to restore healthy gut microbiota and support decolonization of ARB.

Also known as: FMT, Fecal Microbiota Capsules, Stool Transplantation, Human Biome Institute FMT

Fecal Microbiota Transplantation (FMT) group

Probiotic Therapy DIETARY_SUPPLEMENT

Oral administration of a high-dose multistrain probiotic containing Lactobacillus, Bifidobacterium, and Streptococcus strains for 20 days following bowel cleansing.

Also known as: Multistrain Probiotic Supplement, Gut Microbiota Support Supplement

Probiotic therapy group

Gut Microbiota Boosting Diet OTHER

A structured 38-day diet designed to promote eubiosis and support spontaneous ARB decolonization. Meals are tailored and delivered to patients based on clinical nutrition protocols.

Also known as: Microbiota-Stimulating Diet, Dietary Modulation of Gut Flora, Eubiotic Diet

Eubiotic gut microbiota boosting diet group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years;
• Documented intestinal colonization with antibiotic-resistant bacteria confirmed by at least two positive cultures (rectal swabs or, alternatively, stool cultures), with the last positive result obtained at least 28 days prior to the planned procedure;
• Documented colonization by one or more of the following bacterial strains:
• Carbapenem-resistant strains with confirmed resistance mechanisms, including MBL+ (NDM+, VIM+, or others), KPC+, OXA-48+, or phenotypic carbapenem resistance without identified genetic mechanism;
• Multidrug-resistant Enterobacteriaceae resistant to beta-lactams and other antibiotics, especially ESBL-producing strains, including Escherichia, Enterobacter, Klebsiella spp., and/or P. aeruginosa, A. baumannii (commonly associated with the ESKAPE group);
• Gram-positive bacteria such as Enterococcus faecalis, Enterococcus faecium, or other vancomycin-resistant enterococci (VRE), as well as Staphylococcus aureus strains resistant to methicillin (MRSA) and/or vancomycin;
• Absolute neutrophil count (ANC) in peripheral blood \>500/μL within 3 days prior to FMT; In case of tandem or repeated FMTs and expected neutrophil decline, the ANC test should be repeated before each FMT if the interval exceeds 3 days.
• For patients without expected neutropenia (\<500/μL), the blood count remains valid for 28 days;
• Estimated life expectancy of at least 12 months;
• Ability to swallow large capsules (confirmed using a test capsule) or absence of contraindications to colonoscopy;
• No history of anaphylactic shock due to food allergies and ability to tolerate probiotic supplementation;
• Provision of written informed consent to participate in the study.

You may not qualify if:

• Lack of consent to participate in the study or inability to establish logical contact and obtain consent from an authorized representative;
• Absolute neutrophil count (ANC) \< 500 cells/μL on the day of FMT (within 3 days prior) or predicted decline to this level within the next 2 days;
• Diagnosed HIV infection with CD4 lymphocyte count \< 250 cells/μL;
• Active infection requiring antibiotic therapy on the day of FMT or planned antibiotic use during the first 7 days following FMT;
• Symptoms or radiological/endoscopic evidence of gastrointestinal mucosal damage within 7 days prior to FMT (e.g., ulceration, perforation, gastrointestinal bleeding) posing a risk of serious adverse events;
• Contraindications for FMT administration via upper or lower gastrointestinal tract routes (e.g., gastrointestinal perforation, anal atresia, lack of intestinal continuity, or other);
• Inability to undergo preparatory therapy (oral antibiotics: colistin, vancomycin, gentamicin and/or bowel cleansing agents) prior to FMT;
• Inability to swallow large capsules (confirmed with test capsules) or contraindications for colonoscopy;
• Severe food allergy with history of anaphylactic shock or inability to tolerate probiotics;
• Pregnancy or breastfeeding;
• Severe medical conditions contraindicating study protocol adherence as determined by the treating physician (e.g., severe heart failure precluding bowel cleansing due to risk of fluid overload or dehydration);
• Participation in another clinical trial and administration of an investigational drug or device within 3 months prior to randomization;
• Reluctance or inability to comply with protocol requirements, including any physical, mental, or social condition that may impair the participant's ability to adhere to the protocol.

Sponsors & Collaborators

• Medical University of Warsaw: lead
• Human Biome Institute S.A.: collaborator
• Medical Research Agency, Poland: collaborator

Study Sites (1)

Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego, Klinika Hematologii, Transplantologii i Chorób Wewnętrznych

Warsaw, Poland

RECRUITING

MeSH Terms

Interventions

Fecal Microbiota Transplantation

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Central Study Contacts

Jaroslaw Bilinski, MD PhD, Assoc. Prof.

CONTACT

884 299 668; jaroslaw.bilinski@human-biome.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study uses a parallel assignment design where participants are randomly allocated to one of three groups: fecal microbiota transplantation (FMT), probiotic therapy, or a eubiotic gut microbiota-stimulating diet. Each group receives its assigned intervention concurrently without crossover or switching, allowing direct comparison of the interventions' effects on antibiotic-resistant bacteria decolonization.

Study Record Dates

• First Submitted: July 29, 2025
• First Posted: July 31, 2025
• Study Start: December 31, 2024
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): April 30, 2027
• Last Updated: September 3, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share

Locations

PL (1)