FMT for the Decolonization of Carbapenem-resistant Enterobacteriaceae (FMT-CRE)

March 17, 2026 updated by: IANIRO GIANLUCA, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Faecal Microbiota Transplantation to Eradicate Gut Colonisation From Carbapenem-resistant Enterobacteriaceae: a Randomised Controlled Trial

Rates of antimicrobial resistance are increasing worldwide. There is increasing evidence that physiological gut microbiota is a large reservoir of antibiotic-resistance genes. Healthy gut microbiota is known to prevent the colonization of the gastrointestinal tract by pathogens, the so-called mechanism of colonization resistance, but this protective mechanism can be altered by therapies that impair gut microbiota, including antibiotics or chemotherapeutics, with consequent colonisation of gut pathogens, including multi-drug resistant bacteria (MDRB). MDRB carriers represent an epidemiological threat to other hospitalized patients and to the whole community, but are also at risk of developing clinical consequences of this colonization, including bloodstream infections from these pathogens. Fecal microbiota transplantation (FMT) has shown high efficacy in the eradication of recurrent C. difficile infection, and initial evidence suggests that this procedure could be useful in eradicating also MDRB, mainly carbapenem-resistant Enterobacteriaceae.

However, current evidence is mostly limited to case reports and case series, and to a single randomised trial, which was stopped early and did not draw clear conclusion. In a systematic review of 21 studies and 192 patients, eradication rates ranged from 0% to 100%, and authors concluded that larger, well designed randomised controlled trials are needed to further explore this therapy.

The aim of this study is to investigate the efficacy of FMT, compared with placebo FMT, in eradicating gut colonisation from MDRB, focusing on CRE. The investigators will randomize patients colonized by CRE (diagnosed by rectal swab) to FMT from healthy donors or placebo, by colonoscopy. Then, patients will be followed up, rectal swabs will be repeated, and stool samples for culture and microbiome analysis will be collected, up to 3 months after FMT.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Rates of antimicrobial resistance are increasing worldwide. There is increasing evidence that physiological gut microbiota is a large reservoir of antibiotic-resistance genes. Healthy gut microbiota is known to prevent the colonization of the gastrointestinal tract by pathogens, the so-called mechanism of colonization resistance, but this protective mechanism can be altered by therapies that impair gut microbiota, including antibiotics or chemotherapeutics, with consequent colonisation of gut pathogens, including multi-drug resistant bacteria (MDRB). MDRB carriers represent an epidemiological threat to other hospitalized patients and to the whole community, but are also at risk of developing clinical consequences of this colonization, including bloodstream infections from these pathogens. Fecal microbiota transplantation (FMT) has shown high efficacy in the eradication of recurrent C. difficile infection, and initial evidence suggests that this procedure could be useful in eradicating also MDRB, mainly carbapenem-resistant Enterobacteriaceae.

However, current evidence is mostly limited to case reports and case series, and to a single randomised trial, which was stopped early and did not draw clear conclusion. In a systematic review of 21 studies and 192 patients, eradication rates ranged from 0% to 100%, and authors concluded that larger, well designed randomised controlled trials are needed to further explore this therapy.

The extended aims of this study are:

  • To compare the efficacy of donor FMT and placebo FMT in eradicating gut colonisation from CRE
  • To compare the efficacy of donor FMT and placebo FMT in preventing clinical manifestations of gut colonisation from CRE
  • To investigate changes in gut microbiome after treatments

The investigators will carry out a single-centre placebo-controlled, double blind randomised clinical trial of donor FMT vs placebo FMT in carriers of CRE Patients will be recruited among those referred to the infectious disease outpatient clinic of the Fondazione Policlinico Universitario "A. Gemelli". Patients with all inclusion criteria and none of the exclusion criteria (detailed in the specific section of this website) will be considered for this study.

Before randomisation, demographic data will be collected by the infectious disease staff. Moreover, patients will repeat rectal swab and stool culture.

Additionally, patients will be requested to give stool samples to be collected in a sterile, sealed container and stored at -80°C for metagenomic assessment of gut microbiome and meta-transcriptome assessment by the microbiology staff.

After baseline assessments, patients will be randomly assigned to one of the following treatment arms:

  • Donor FMT (D-FMT)
  • Placebo FMT (P-FMT)

Patients in both groups will undergo a single FMT procedure by colonoscopy. Each patient in the donor FMT group will receive faeces from one single donor. Placebo FMT will be made of 250 mL water. The selection of stool donors will be performed by the gastroenterology staff following protocols previously recommended by international guidelines and according the new recommendation imposed by the reorganisation of faecal microbiota transplant during the COVID-19 pandemic (Ianiro et al. - Gut 2020) The assignment of faecal infusates from healthy donors to patients will be done randomly, without any specific recipient-donor match, as this is not recommended by international guidelines All faecal infusates will be manufactured in the microbiology unit of our hospital. Only frozen faeces will be used. Preparation of frozen faeces will follow protocols from international guidelines.

Follow-up visits will be performed by physicians from the gastroenterology and the infectious disease unit. All patients will be followed up for 3 months after the end of treatments. Follow-up visits will be scheduled at week 1, week 2, week 4, and week 12, after the end of treatments, respectively. At each visit the following assessments will be performed: 1) rectal swab for MDRB; 2) collection of stool samples for stool culture ; 3) collection of stool samples for microbiome analysis; 4) record of adverse events. Unscheduled follow-up visits will be offered if requested by the patients.

Study Outcomes are detailed in the specific section of this website.

The statistical analysis will be performed both on an intention-to-treat and per-protocol basis. Differences among groups will be assessed with a two-tailed Wilcoxon-rank sum test for continuous data and with Fisher's exact probability test (using two-tailed P-values) for categorical data. Differences in cure percentages will be determined with Fisher's exact test (with two-tailed P values). For microbiome analysis, statistical differences between group means will be calculated using a two-tailed Wilcoxon-Rank Sum Test, through the R statistical software package (R Core Team, Vienna, Austria).

Study Type

Interventional

Enrollment (Estimated)

52

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion criteria

  • 18 years old or older
  • Current evidence of gut colonisation (diagnosed with rectal swab) by CRE
  • Ability to give their consent to be included in the study.

Exclusion criteria

  • Another known gastrointestinal infection apart from C. difficile infection
  • Known active gastrointestinal disorders (e.g. infectious gastroenteritis, coeliac disease, inflammatory bowel disease, irritable bowel syndrome, chronic pancreatitis, biliary salt diarrhoea)
  • Previous colorectal surgery or cutaneous stoma
  • Food allergies
  • Current or recent (<2 weeks) therapy with drugs that could possibly alter gut microbiota (e.g. antimicrobials, probiotics, proton pump inhibitors, immunosuppressants, metformin)
  • Decompensated heart failure or heart disease with ejection fraction lower than 30%
  • Severe respiratory insufficiency
  • Psychiatric disorders
  • Pregnancy
  • Unable to give informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Donor FMT
Patients enrolled in this arm will receive donor FMT
Biological: Donor FMT
This intervention is represented by the administration, in the recipients' gut, of donor microbiota through FMT
Placebo Comparator: Placebo FMT
Patients enrolled in this arm will receive placebo FMT (that will be made of water)
Other: Placebo FMT
This intervention is represented by the administration, in the recipients' gut, of a placebo through FMT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants who will obtain an eradication of CRE carriage after treatments
Time Frame: 4 weeks
The investigators will evaluate the number of participants who will obtain eradication of CRE carriage after treatments, at 4 weeks-follow-up, evaluated through rectal swab for CRE
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants who will obtain an eradication of CRE carriage after treatments
Time Frame: 12 weeks
The investigators will evaluate the number of participants who will obtain eradication of CRE carriage after treatments, at 1,2 and 12 weeks-follow-up, evaluated through rectal swab for CRE
12 weeks
Number of participants with significant increase in alpha-diversity and beta-diversity of their gut microbiota after treatments
Time Frame: 12 weeks
Throughout the study period (12 weeks) the investigators will evaluate the number of participants with significant increase in alpha-diversity (assessed by Shannon index) and beta-diversity (assessed by Bray-Curtis dissimilarity) of their gut microbiota after treatments, compared with baseline
12 weeks
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame: 12 weeks
The number of participants with treatment-related adverse events (assessed by CTCAE v4.0) will be recorded throughout the study period (12 weeks)
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Investigators

  • Principal Investigator: Gianluca Ianiro, Fondazione Policlinico Gemelli IRCCS

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 18, 2021

Primary Completion (Actual)

March 18, 2026

Study Completion (Estimated)

August 15, 2026

Study Registration Dates

First Submitted

February 13, 2021

First Submitted That Met QC Criteria

February 13, 2021

First Posted (Actual)

February 17, 2021

Study Record Updates

Last Update Posted (Actual)

March 19, 2026

Last Update Submitted That Met QC Criteria

March 17, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3556

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data will be available to other researchers

IPD Sharing Time Frame

data will be available after the completion of the study, for 5 years

IPD Sharing Access Criteria

Data will be given upon reasonable request to the PI

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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