Fecal Microbiota Transplantation for Eradication of CRE

NCT03167398 | Completed Phase 1

• 1 other identifier: 0215-17-RMB-CTIL
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Antibiotic Resistant Strain; Microbial Colonization

Keywords

fecal microbiota transplantation; carbapenem-resistant enterobacteriaceae; multidrug resistant bacteria; carrier

Outcome Measures

Primary Outcomes (1)

• CRE eradication on rectal stool samples

  3 consecutive negative rectal samples for CRE

  1 month after intervention

Study Arms (1)

CRE carriers

EXPERIMENTAL

Fecal Microbiota Transplantation

Biological: Fecal Microbiota Transplantation

Interventions

Fecal Microbiota Transplantation BIOLOGICAL

Patients able to swallow will be given capsulized FMT using 15 capsules a day for two consecutive days. Patients will be treated concomitantly with omeprazole 20mg once in the evening before FMT and daily for the next 2 days.

CRE carriers

Eligibility Criteria

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

You may qualify if:

• Adult inpatients ≥18 years positive for CRE of any strain and resistance mechanism in rectal surveillance stool samples, with or without CRE clinical samples. A positive rectal swab within one week before randomization will be mandatory.

You may not qualify if:

• Pregnant women
• Patients with severe neutropenia (\<100/µl)
• Surgical patients with perfurated viscous

Sponsors & Collaborators

• Rambam Health Care Campus: lead
• Tel-Aviv Sourasky Medical Center: collaborator

Study Sites (1)

Rambam Health Care Campus

Haifa, Israel

Location

Related Publications (1)

• Bar-Yoseph H, Carasso S, Shklar S, Korytny A, Even Dar R, Daoud H, Nassar R, Maharshak N, Hussein K, Geffen Y, Chowers Y, Geva-Zatorsky N, Paul M. Oral Capsulized Fecal Microbiota Transplantation for Eradication of Carbapenemase-producing Enterobacteriaceae Colonization With a Metagenomic Perspective. Clin Infect Dis. 2021 Jul 1;73(1):e166-e175. doi: 10.1093/cid/ciaa737.

  PMID: 32511695 DERIVED

MeSH Terms

Conditions

Communicable Diseases

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2017
• First Posted: May 30, 2017
• Study Start: February 1, 2018
• Primary Completion: December 30, 2019
• Study Completion: December 30, 2019
• Last Updated: January 27, 2020

Record last verified: 2020-01

Locations

IL (1)