Effectiveness of Fecal Flora Alteration for Eradication of Carbapenemase-producing Enterobacteriaceae Colonization

NCT03802461 | Suspended Phase 2 DMC

• 1 other identifier: 18-5177
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 13

Brief Summary

Carbapenemase-producing Enterobacteriaceae (CPE) are bacteria carried in the gastrointestinal tract that are resistant to carbapenems, antibiotics of last resort. CPE infections result in death in 25-50% of cases. Fecal microbiota transplantation (FMT) is the transfer of stool from a healthy donor to a recipient to alter the composition of gut microbes. Early studies support its use for eliminating CPE carriage but definitive studies are lacking. The investigators propose a feasibility pilot for a multicenter, non-blinded randomized trial comparing the effectiveness of FMT with no intervention (standard of care) in eliminating intestinal carriage of CPE. Forty patients with CPE will be randomly assigned to receive FMT by enema or no intervention. Feasibility will be demonstrated by the ability to recruit and retain 40 patients over 12 months, and to provide FMT made at a central site to at least one off-site hospital. The primary clinical endpoint for the full trial is CPE intestinal carriage 3 months after the intervention. Secondary endpoints include: CPE carriage at 1, 6 and 12 months; time to decolonization of CPE; safety; CPE infections over 12 months; and, intestinal carriage of other antibiotic-resistant organisms. Data on the clinical outcomes will be collected but not analyzed in this feasibility study.

Conditions

Infection

Keywords

Fecal Microbiota Transplantation; Gut Microbiome; Carbapenemase-producing Enterobacteriaceae (CPE)

Outcome Measures

Primary Outcomes (3)

• Incidence of intestinal colonization of patients with CPE 3 months after intervention.

  Incidence of CPE colonization in FMT arm vs control arm at 3 months

  3 months

• Randomization rate in study

  Completion of randomization of 40 study participants during the study period will be used to indicate feasibility of the study.

  12 months

• Proportion of patients retained in study for up to 6 months

  A retention of 90% of patients up to 6 months in the study will be used to indicate feasibility.

  6 months

Secondary Outcomes (6)

• Incidence of CPE decolonization in FMT-treatment and non-treatment groups at 1, 6 and 12 months.

  1, 6, and 12 months

• Time to CPE decolonization in FMT-treatment and non-treatment groups.

  1, 3, 6, and 12 months

• Incidence of CPE clinical infection in FMT treatment and non-treatment groups over 12 months.

  1, 3, 6, and 12 months

• Incidence of extended spectrum beta-lactamase organisms (ESBL) and vancomycin-resistant Enterococci (VRE) intestinal colonization at 0, 1, 3, 6 and 12 months in FMT treatment and non-treatment groups.

  1, 3, 6, and 12 months

• Incidence of solicited and unsolicited adverse and serious adverse events in both groups

  3 months

Other Outcomes (1)

• Changes in composition and diversity of fecal bacterial phyla (as measured by 16s ribosomal ribonucleic acid sequencing) in both intervention groups

  12 months

Study Arms (2)

Fecal Microbiota Transplantation (FMT)

ACTIVE COMPARATOR

Bowel lavage preparation followed by FMT administered by enema, given on 3 occasions. Fecal filtrate for FMT will be prepared from 50 g of healthy donor stool, homogenized, and diluted in 300 mL sterile normal saline.

Biological: Fecal Microbiota Transplantation (FMT)

Standard of Care

NO INTERVENTION

Patients in this arm will not receive intervention and will be on standard of care .

Interventions

Fecal Microbiota Transplantation (FMT) BIOLOGICAL

Feces from healthy donor

Fecal Microbiota Transplantation (FMT)

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years
• ≥ 1 rectal swab, groin, stool, or urine specimen positive for a CPE within the past 1 month.
• Presence of CPE will be confirmed at baseline through collection of pooled groin/rectal swab and urine specimen.
• Women of childbearing age must be using at least one reliable form of birth control.
• Must be able to provide informed consent.

You may not qualify if:

• Active infection with CPE at the time of assessment.
• Pregnancy, planned pregnancy or breastfeeding.
• Current admission to intensive care unit.
• Significantly immunocompromised patients .
• neutropenia (ANC \< 1)
• ongoing use of systemic corticosteroids \> 30 mg/day
• ongoing use of biologic therapy
• undergoing chemotherapy, received chemotherapy ≤ 30 days from baseline visit, or expected to undergo chemotherapy in the upcoming 12 months
• active hematologic malignancy
• solid organ transplant recipient
• hematopoetic stem cell transplant recipient
• HIV positive patients with cluster differentiation 4 (CD4) cell count \< 350
• Patients with ascites or receiving peritoneal dialysis.
• History of inflammatory bowel disease (Crohn's or Ulcerative colitis).
• Chronic diarrhea or active colitis for any reason.

Sponsors & Collaborators

• Susy Hota: lead
• Sinai Health System, Ontario, Canada: collaborator
• University of Toronto, Ontario, Canada: collaborator
• The Toronto Invasive Bacterial Diseases Network, Ontario, Canada: collaborator
• Public Health Ontario Laboratories, Ontario, Canada: collaborator

Study Sites (13)

William Osler Health System

Brampton, Ontario, L6R 3J7, Canada

Location

Joseph Brant Hospital

Burlington, Ontario, L7S 1W7, Canada

Location

Lakeridge Health

Oshawa, Ontario, L1G 2B9, Canada

Location

MacKenzie Health

Richmond Hill, Ontario, L4C 4Z3, Canada

Location

The Scarborough Hospital

Scarborough Village, Ontario, M1P 2T7, Canada

Location

North York General Hospital

Toronto, Ontario, M2K 1E1, Canada

Location

Michael Garron Hospital

Toronto, Ontario, M4C 3E7, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

St Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

University Health Network

Toronto, Ontario, M5B 1W8, Canada

Location

Public Health Ontario Laboratories

Toronto, Ontario, M5G 1M1, Canada

Location

Sinai Health System

Toronto, Ontario, M5G 1X5, Canada

Location

St. Joseph Health Centre

Toronto, Ontario, M6R 1B5, Canada

Location

MeSH Terms

Conditions

Infections

Interventions

Fecal Microbiota Transplantation

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Susy S. Hota, MD MSc FRCPC

  Infectious Diseases Physician, University Health Network

  PRINCIPAL INVESTIGATOR

• Susan M. Poutanen, MD MPH FRCPC

  Microbiologist & Infectious Disease Physician, Sinai Health System

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical Director, Infection Prevention and Control

Model Details: Asymptomatic adult patients intestinally colonized with CPE will either randomized to receive fecal microbiota transplantation (intervention) or standard of care (no intervention).

Study Record Dates

• First Submitted: November 8, 2018
• First Posted: January 14, 2019
• Study Start: March 22, 2019
• Primary Completion: December 15, 2023
• Study Completion: March 20, 2024
• Last Updated: November 3, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (13)