FMT for the Decolonization of Carbapenem-resistant Enterobacteriaceae

NCT04759001 | Recruiting Phase 1

• 1 other identifier: 3556
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Enterobacteriaceae Infections; Multi-antibiotic Resistance

Keywords

Fecal microbiota transplantation; Enterobacteriaceae; Multi-drug resistant bacteria

Outcome Measures

Primary Outcomes (1)

• Number of participants who will obtain an eradication of CRE carriage after treatments

  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 Outcomes (3)

• Number of participants who will obtain an eradication of CRE carriage after treatments

  12 weeks

• Number of participants with significant increase in alpha-diversity and beta-diversity of their gut microbiota after treatments

  12 weeks

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  12 weeks

Study Arms (2)

Donor FMT

EXPERIMENTAL

Patients enrolled in this arm will receive donor FMT

Biological: Donor FMT

Placebo FMT

PLACEBO COMPARATOR

Patients enrolled in this arm will receive placebo FMT (that will be made of water)

Other: Placebo FMT

Interventions

Donor FMT BIOLOGICAL

This intervention is represented by the administration, in the recipients' gut, of donor microbiota through FMT

Donor FMT

Placebo FMT OTHER

This intervention is represented by the administration, in the recipients' gut, of a placebo through FMT

Placebo FMT

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Digestive Disease Center, Fondazione Policlinico Univesitario A. Gemelli IRCCS

Rome, 00168, Italy

RECRUITING

Related Publications (5)

• Pitout JD, Laupland KB. Extended-spectrum beta-lactamase-producing Enterobacteriaceae: an emerging public-health concern. Lancet Infect Dis. 2008 Mar;8(3):159-66. doi: 10.1016/S1473-3099(08)70041-0.

  PMID: 18291338 BACKGROUND

• Huttner BD, de Lastours V, Wassenberg M, Maharshak N, Mauris A, Galperine T, Zanichelli V, Kapel N, Bellanger A, Olearo F, Duval X, Armand-Lefevre L, Carmeli Y, Bonten M, Fantin B, Harbarth S; R-Gnosis WP3 study group. A 5-day course of oral antibiotics followed by faecal transplantation to eradicate carriage of multidrug-resistant Enterobacteriaceae: a randomized clinical trial. Clin Microbiol Infect. 2019 Jul;25(7):830-838. doi: 10.1016/j.cmi.2018.12.009. Epub 2019 Jan 4.

  PMID: 30616014 BACKGROUND

• Cammarota G, Ianiro G, Kelly CR, Mullish BH, Allegretti JR, Kassam Z, Putignani L, Fischer M, Keller JJ, Costello SP, Sokol H, Kump P, Satokari R, Kahn SA, Kao D, Arkkila P, Kuijper EJ, Vehreschild MJG, Pintus C, Lopetuso L, Masucci L, Scaldaferri F, Terveer EM, Nieuwdorp M, Lopez-Sanroman A, Kupcinskas J, Hart A, Tilg H, Gasbarrini A. International consensus conference on stool banking for faecal microbiota transplantation in clinical practice. Gut. 2019 Dec;68(12):2111-2121. doi: 10.1136/gutjnl-2019-319548. Epub 2019 Sep 28.

  PMID: 31563878 BACKGROUND

• Ianiro G, Mullish BH, Kelly CR, Kassam Z, Kuijper EJ, Ng SC, Iqbal TH, Allegretti JR, Bibbo S, Sokol H, Zhang F, Fischer M, Costello SP, Keller JJ, Masucci L, van Prehn J, Quaranta G, Quraishi MN, Segal J, Kao D, Satokari R, Sanguinetti M, Tilg H, Gasbarrini A, Cammarota G. Reorganisation of faecal microbiota transplant services during the COVID-19 pandemic. Gut. 2020 Sep;69(9):1555-1563. doi: 10.1136/gutjnl-2020-321829. Epub 2020 Jul 3.

  PMID: 32620549 BACKGROUND

• Saha S, Tariq R, Tosh PK, Pardi DS, Khanna S. Faecal microbiota transplantation for eradicating carriage of multidrug-resistant organisms: a systematic review. Clin Microbiol Infect. 2019 Aug;25(8):958-963. doi: 10.1016/j.cmi.2019.04.006. Epub 2019 Apr 12.

  PMID: 30986562 BACKGROUND

MeSH Terms

Conditions

Enterobacteriaceae Infections

Condition Hierarchy (Ancestors)

Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Gianluca Ianiro

  Fondazione Policlinico Gemelli IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gianluca Ianiro

CONTACT

3381929859; gianluca.ianiro@hotmail.it

Serena Porcari

CONTACT

porcariserena89@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: To mask treatments to physicisans and recipients, both FMT bottles and syringes will be covered with dark-coloured paper before the infusion, and the patients will be unable to see the endoscopic display during the procedure. Moreover, the physicians who will evsaluate patients at follow-up will not aware of the treatment being administered.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Randomized controlled trial

Study Record Dates

• First Submitted: February 13, 2021
• First Posted: February 17, 2021
• Study Start: February 18, 2021
• Primary Completion: March 18, 2026
• Study Completion (Estimated): August 15, 2026
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: data will be available after the completion of the study, for 5 years
• Access Criteria: Data will be given upon reasonable request to the PI

Locations

IT (1)