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Fecal Microbiota Transplantation for Carbapenem-resistant Enterobacteriaceae

Primary Purpose

Carbapenem-Resistant Enterobacteriaceae Infection

Status
Completed
Phase
Phase 2
Locations
Israel
Study Type
Interventional
Intervention
FMT
Sponsored by
Rambam Health Care Campus
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carbapenem-Resistant Enterobacteriaceae Infection

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

We will include adult inpatients ≥18 years positive for CRE of any strain and resistance mechanism in rectal surveillance stool samples, with or without CRE clinical samples. We will mandate a positive rectal swab within one week before randomization. Several exclusion criteria may change throughout the patients' hospitalization and we will follow-up patients for these criteria until reaching eligibility or not (designed as (for follow-up)). Non-eligible patients discharged will be re-evaluated for inclusion when re-admitted.

We will exclude:

  • Pregnant women
  • Patients with severe neutropenia (<100/µl) (for follow-up)
  • Severe GVHD involving the gastrointestinal involvment (for follow-up)
  • Patients with inflammatory bowel disease (Crohn's or ulcerative colitis)
  • Patients with intestinal perforation or severe abdominal infection (for follow-up)
  • Patients carrying a colostomy, ileostomy or similar
  • Inability or contra-indication to take oral medications (intestinal obstruction, suspected perforation, peritonitis) (for follow-up)
  • Severe food allergies
  • Severe diarrhea (for follow-up)
  • Inability to provide informed consent (for follow-up)
  • Refusal of primary care physician
  • Patients treated with antibiotics within the 2 days before fulfilling all other eligibility criteria (for follow-up)

Sites / Locations

  • Rambam Health Care Campus

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Fecal microbiota transplantation (FMT)

Control

Arm Description

FMT regimen: Patients will be given capsulized FMT 15 capsules a day for two consecutive days after a fast of 8 hours before FMT. Stool will be collected before and after the intervention for genomic analysis of CRE strains, analysis of microbiome and metabolome.

Routine follow-up

Outcomes

Primary Outcome Measures

CRE eradication
Number of participants achieving CRE eradication at 28 days, defined as 3 consecutive negative rectal cultures, with polymerase chain reaction preformed in the last sample. For patients with clinical infections, eradication definition will include a negative culture from the site of infection, if relevant at the time of eradication.

Secondary Outcome Measures

CRE eradication rates at day 7, day 14, and 3 & 6 months
Number of participants achieving CRE eradication rates at day 7, day 14, and 3 & 6 months
Mortality
Number of participants who died by 28-day and 6 month
Bacteremia
Number of participants with CRE bacteremia and any bacteremia
CRE infection
Number of participants with non-bacteremic new clinically-significant CRE infections
Hospitalization days
Totals days in-hospital
Adverse events
Number of participants with: pneumonia within a week after the intervention; dyspeptic complaints collected at the time of rectal sampling; changes in bowel habit including diarrhea and constipation; discontinuation of FMT before completing the study protocol

Full Information

First Posted
October 29, 2019
Last Updated
November 22, 2022
Sponsor
Rambam Health Care Campus
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1. Study Identification

Unique Protocol Identification Number
NCT04146337
Brief Title
Fecal Microbiota Transplantation for Carbapenem-resistant Enterobacteriaceae
Official Title
Fecal Microbiota Transplantation for Eradication of Carbapenem-resistant Enterobacteriaceae Colonization: Randomized Control Trial
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
October 12, 2020 (Actual)
Primary Completion Date
December 31, 2021 (Actual)
Study Completion Date
June 30, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rambam Health Care Campus

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
2:1, open-label, single center, randomized controlled trial comparing FMT vs. no intervention for CRE carriers,
Detailed Description
Antibiotic resistance has emerged worldwide and is of major concern leading to multidrug resistant (MDR) bacteria that are widely spread and are 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 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 investigators aim to assess the effects of FMT on colonization and clinical infections with CRE. The investigators 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 time-point in the following 6 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carbapenem-Resistant Enterobacteriaceae Infection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Fecal microbiota transplantation (FMT)
Arm Type
Experimental
Arm Description
FMT regimen: Patients will be given capsulized FMT 15 capsules a day for two consecutive days after a fast of 8 hours before FMT. Stool will be collected before and after the intervention for genomic analysis of CRE strains, analysis of microbiome and metabolome.
Arm Title
Control
Arm Type
No Intervention
Arm Description
Routine follow-up
Intervention Type
Biological
Intervention Name(s)
FMT
Intervention Description
Fecal microbiota in frozen capsules
Primary Outcome Measure Information:
Title
CRE eradication
Description
Number of participants achieving CRE eradication at 28 days, defined as 3 consecutive negative rectal cultures, with polymerase chain reaction preformed in the last sample. For patients with clinical infections, eradication definition will include a negative culture from the site of infection, if relevant at the time of eradication.
Time Frame
28 days
Secondary Outcome Measure Information:
Title
CRE eradication rates at day 7, day 14, and 3 & 6 months
Description
Number of participants achieving CRE eradication rates at day 7, day 14, and 3 & 6 months
Time Frame
days 7, 14, months 3, 6
Title
Mortality
Description
Number of participants who died by 28-day and 6 month
Time Frame
28-day and 6 months
Title
Bacteremia
Description
Number of participants with CRE bacteremia and any bacteremia
Time Frame
6 months
Title
CRE infection
Description
Number of participants with non-bacteremic new clinically-significant CRE infections
Time Frame
6 months
Title
Hospitalization days
Description
Totals days in-hospital
Time Frame
6 months
Title
Adverse events
Description
Number of participants with: pneumonia within a week after the intervention; dyspeptic complaints collected at the time of rectal sampling; changes in bowel habit including diarrhea and constipation; discontinuation of FMT before completing the study protocol
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
We will include adult inpatients ≥18 years positive for CRE of any strain and resistance mechanism in rectal surveillance stool samples, with or without CRE clinical samples. We will mandate a positive rectal swab within one week before randomization. Several exclusion criteria may change throughout the patients' hospitalization and we will follow-up patients for these criteria until reaching eligibility or not (designed as (for follow-up)). Non-eligible patients discharged will be re-evaluated for inclusion when re-admitted. We will exclude: Pregnant women Patients with severe neutropenia (<100/µl) (for follow-up) Severe GVHD involving the gastrointestinal involvment (for follow-up) Patients with inflammatory bowel disease (Crohn's or ulcerative colitis) Patients with intestinal perforation or severe abdominal infection (for follow-up) Patients carrying a colostomy, ileostomy or similar Inability or contra-indication to take oral medications (intestinal obstruction, suspected perforation, peritonitis) (for follow-up) Severe food allergies Severe diarrhea (for follow-up) Inability to provide informed consent (for follow-up) Refusal of primary care physician Patients treated with antibiotics within the 2 days before fulfilling all other eligibility criteria (for follow-up)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Haggay Bar Yoseph, MD
Organizational Affiliation
Rambam Health Care Campus
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rambam Health Care Campus
City
Haifa
Country
Israel

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Share by contact with authors
IPD Sharing Time Frame
End of study
IPD Sharing Access Criteria
Academic use

Learn more about this trial

Fecal Microbiota Transplantation for Carbapenem-resistant Enterobacteriaceae

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