Fecal Microbiota Transplantation for Carbapenem-resistant Enterobacteriaceae

NCT ID: NCT04146337

Last Updated: 2022-11-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-12
• Study Completion Date: 2022-06-30

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.

Conditions

Carbapenem-Resistant Enterobacteriaceae Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Fecal microbiota transplantation (FMT)

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.

Group Type: EXPERIMENTAL

FMT

Intervention Type: BIOLOGICAL

Fecal microbiota in frozen capsules

Control

Routine follow-up

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

FMT

Fecal microbiota in frozen capsules

Intervention Type: BIOLOGICAL

Eligibility Criteria

Exclusion Criteria

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rambam Health Care Campus

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Haggay Bar Yoseph, MD

Role: PRINCIPAL_INVESTIGATOR

Rambam Health Care Campus

Locations

Rambam Health Care Campus

Haifa, , Israel

Countries

Israel

Other Identifiers

0338-19

Identifier Type: -

Identifier Source: org_study_id