NCT03167398

Fecal Microbiota Transplantation for Eradication of CRE

Completed Phase 1, PHASE2 Last updated 27 January 2020

What this trial tests

Phase 1, PHASE2 trial testing Fecal Microbiota Transplantation in Antibiotic Resistant Strain in 15 participants. Completed in 30 December 2019.

Timeline

1 February 2018

Primary endpoint
30 December 2019

30 December 2019

Quick facts

Lead sponsor	Rambam Health Care Campus
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	prevention
Enrollment	15
Start date	1 February 2018
Primary completion	30 December 2019
Estimated completion	30 December 2019
Sites	1 location across Israel

Drugs / interventions tested

• Fecal Microbiota Transplantation — full drug profile →

Conditions studied

• Antibiotic Resistant Strain — all drugs for Antibiotic Resistant Strain →
• Microbial Colonization — all drugs for Microbial Colonization →

Sponsor

Rambam Health Care Campus — full company profile →

Who can join

18 and older, any sex, with Antibiotic Resistant Strain or Microbial Colonization. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Antibiotic resistance has emerged world wide and is of major concern. Multi-drug resistant (MDR) bacteria is widely spread and is now a major factor in morbidity and mortality in health-care settings. Among MDRs, carbapenem-resistant Enterobacteriaceae (CRE) are of special concern, receiving the highest classification of "urgent threat level" in the US President Report. Consistent mortality rates of 40-50% are observed among inpatients with infections caused by CRE in hospitals worldwide, related mainly to unavailable, delayed or ineffective antibiotic treatment options.

The extremely high mortality rates of patients with CRE infections have driven efforts to prevent the acquisition and spread of these bacteria in hospitals. These include screening for carriage, contact isolation of carriers, cohorting, dedicated healthcare staff and other infection control measures. These strategies have been proven as effective but are cumbersome and expensive. In most locations these strategies failed to completely eradicate CRE endemicity.

CRE decolonization (eradication of colonization) might offer a double benefit - reducing the risk for the individual carrier to develop an infection due to the resistant strain (by that, potentially lowering the mortality risk) and preventing the bacteria from spreading to other patients, exposing them to the same hazard.

Fecal microbiota transplantation (FMT), in which fecal material enriched with commensal microorganisms is transferred from a healthy donor, have proven efficacy in the treatment of recurrent Clostridium difficile infection (CDI) in multiple trails. Major adverse events that has been reported so far are mostly related to the route of administration (aspiration during nasogastric tube administration/colonoscopy). Other adverse events include mostly GI related symptoms (diarrhea, nausea, belching) and are self limited and resolve in few hours. FMT seems to be safe and effective both in immunocompetent and immunocompromised patients.

The high efficacy of FMT in the treatment of a multi-drug resistant pathogen such as Clostridium difficile, suggest that it might be an efficient tool for other MDR pathogens (e.g. CRE).

The authors aim to assess the effects of FMT on colonization and clinical infections with CRE. The potential of FMT to restore the gut microbiome and compete with residual resistant strains offer a novel way to fight the current MDR epidemic.

The authors will apply FMT on a cohort of CRE carriers in a single center in Israel. FMT will be given by capsules for 2 consecutive days followed by rectal sampling at predefined timepoint in the following 6 months.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Fecal microbiota transplantation beyond Clostridioides difficile infections.
   Wortelboer K, Nieuwdorp M, Herrema H. · · 2019 · cited 111× · PMID 31201141 · DOI 10.1016/j.ebiom.2019.05.066
2. Gut Microbiota Modulation for Multidrug-Resistant Organism Decolonization: Present and Future Perspectives.
   Gargiullo L, Del Chierico F, D'Argenio P, Putignani L. · · 2019 · cited 54× · PMID 31402904 · DOI 10.3389/fmicb.2019.01704
3. Oral Capsulized Fecal Microbiota Transplantation for Eradication of Carbapenemase-producing Enterobacteriaceae Colonization With a Metagenomic Perspective.
   Bar-Yoseph H, Carasso S, Carasso S, Shklar S, et al · · 2021 · cited 51× · PMID 32511695 · DOI 10.1093/cid/ciaa737
4. Multidrug-Resistant Gram-Negative Bacteria Decolonization in Immunocompromised Patients: A Focus on Fecal Microbiota Transplantation.
   Alagna L, Palomba E, Mangioni D, Bozzi G, et al · · 2020 · cited 20× · PMID 32764526 · DOI 10.3390/ijms21165619
5. Is there a role of faecal microbiota transplantation in reducing antibiotic resistance burden in gut? A systematic review and Meta-analysis.
   Dharmaratne P, Rahman N, Leung A, Ip M. · · 2021 · cited 17× · PMID 34170204 · DOI 10.1080/07853890.2021.1927170
6. Bacterial, Gut Microbiome-Modifying Therapies to Defend against Multidrug Resistant Organisms.
   Feehan A, Garcia-Diaz J. · · 2020 · cited 14× · PMID 31991615 · DOI 10.3390/microorganisms8020166
7. The Role of Fecal Microbiota Transplantation in the Allogeneic Stem Cell Transplant Setting.
   Metafuni E, Di Marino L, Giammarco S, Bellesi S, et al · · 2023 · cited 7× · PMID 37764025 · DOI 10.3390/microorganisms11092182
8. Engineering coupled consortia-based biosensors for diagnostic.
   Huang R, Kravchik V, Zaatry R, Habib M, et al · · 2025 · cited 1× · PMID 40263365 · DOI 10.1038/s41467-025-58996-9