Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Effectiveness of Fecal Flora Alteration for Eradication of Carbapenemase-producing Enterobacteriaceae Colonization (EFFECT-CPE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03802461
Recruitment Status : Recruiting
First Posted : January 14, 2019
Last Update Posted : April 1, 2019
Sponsor:
Collaborators:
Sinai Health System, Ontario, Canada
University of Toronto, Ontario, Canada
The Toronto Invasive Bacterial Diseases Network, Ontario, Canada
Public Health Ontario Laboratories, Ontario, Canada
Information provided by (Responsible Party):
Susy Hota, University Health Network, Toronto

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.

Condition or disease Intervention/treatment Phase
Infection Biological: Fecal Microbiota Transplantation (FMT) Phase 2 Phase 3

Detailed Description:
This is a multisite, open-label randomized controlled internal pilot trial designed to assess the feasibility of a larger trial aimed at determining the effectiveness of fecal microbiota transplantation (FMT) by enema in short and long term intestinal decolonization of carbapenemase-producing Enterobacteriaceae (CPE). Forty (40) asymptomatic adult patients intestinally colonized with CPE will be allocated in a 1:1 ratio to receive a bowel preparation followed by FMT by enema route, versus standard of care (no intervention). FMT will be provided by the University of Toronto Microbiota Therapeutics Outcomes Program (MTOP), using standardized operating procedures for recruiting and screening FMT donors, manufacturing FMT and administering FMT by enema. The feasibility outcomes are: successful randomization of 40 patients within 12 months, retention of >90% (36/40) of patients up to 6 months, and provision of FMT at a non-primary study site in at least one patient. Data on the clinical and exploratory outcomes will be collected but not analyzed in this pilot study. The primary clinical outcome is incidence of intestinal decolonization of CPE at 3 months. Secondary clinical outcomes include: time to decolonization of CPE; incidence of CPE clinical infections up to 12 months post-intervention; incidence of intestinal decolonization of CPE and other antibiotic-resistant organisms (extended spectrum beta-lactamase Enterobacteriaceae - ESBLs and vancomycin-resistant Enterococci - VRE) at 1, 3, 6 and 12 months post-intervention; and, safety profile. As an exploratory outcome, changes in fecal microbiome composition will be examined before and after intervention. This study leverages existing support, research infrastructures and expertise - including the Toronto Invasive Bacterial Diseases Network (TIBDN), Toronto Antimicrobial Resistance Research Network (TARRN), and the University of Toronto Microbiota Therapeutics Outcomes Program (MTOP) - to optimize feasibility regarding patient recruitment and FMT administration.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Asymptomatic adult patients intestinally colonized with CPE will either randomized to receive fecal microbiota transplantation (intervention) or standard of care (no intervention).
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effectiveness of Fecal Flora Alteration for Eradication of Carbapenemase-producing Enterobacteriaceae Colonization Trial (EFFECT-CPE): a Multisite, Open-label, Randomized Controlled Feasibility Pilot Trial
Actual Study Start Date : March 22, 2019
Estimated Primary Completion Date : July 15, 2020
Estimated Study Completion Date : December 20, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bowel Movement

Arm Intervention/treatment
Active Comparator: Fecal Microbiota Transplantation (FMT)
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)
Feces from healthy donor

No Intervention: Standard of Care
Patients in this arm will not receive intervention and will be on standard of care .



Primary Outcome Measures :
  1. Incidence of intestinal colonization of patients with CPE 3 months after intervention. [ Time Frame: 3 months ]
    Incidence of CPE colonization in FMT arm vs control arm at 3 months

  2. Randomization rate in study [ Time Frame: 12 months ]
    Completion of randomization of 40 study participants during the study period will be used to indicate feasibility of the study.

  3. Proportion of patients retained in study for up to 6 months [ Time Frame: 6 months ]
    A retention of 90% of patients up to 6 months in the study will be used to indicate feasibility.


Secondary Outcome Measures :
  1. Incidence of CPE decolonization in FMT-treatment and non-treatment groups at 1, 6 and 12 months. [ Time Frame: 1, 6, and 12 months ]
    As above

  2. Time to CPE decolonization in FMT-treatment and non-treatment groups. [ Time Frame: 1, 3, 6, and 12 months ]
    As above

  3. Incidence of CPE clinical infection in FMT treatment and non-treatment groups over 12 months. [ Time Frame: 1, 3, 6, and 12 months ]
    As above

  4. 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. [ Time Frame: 1, 3, 6, and 12 months ]
    Changes in colonization status of other antimicrobial resistant organisms over the study period

  5. Incidence of solicited and unsolicited adverse and serious adverse events in both groups [ Time Frame: 3 months ]
    Participants will be asked to report adverse and serious adverse events will be throughout the study period and will be asked specifically about adverse events during study visits

  6. Number of patients with all-cause mortality at 30 days post-randomization [ Time Frame: 1 month ]
    As above


Other Outcome Measures:
  1. Changes in composition and diversity of fecal bacterial phyla (as measured by 16s ribosomal ribonucleic acid sequencing) in both intervention groups [ Time Frame: 12 months ]
    As above



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 18 years
  2. ≥ 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.

  3. Women of childbearing age must be using at least one reliable form of birth control.
  4. Must be able to provide informed consent.

Exclusion Criteria:

  1. Active infection with CPE at the time of assessment.
  2. Pregnancy, planned pregnancy or breastfeeding.
  3. Current admission to intensive care unit.
  4. 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
  5. Patients with ascites or receiving peritoneal dialysis.
  6. History of inflammatory bowel disease (Crohn's or Ulcerative colitis).
  7. Chronic diarrhea or active colitis for any reason.
  8. Ileus or active gastrointestinal motility disorder at baseline.
  9. History of total colectomy.
  10. Severe, irreversible bleeding disorder.
  11. History of anaphylactic or anaphylactoid allergic reaction to any foods.
  12. Anticipated life expectancy less than 6 months.
  13. Unable to tolerate enema.
  14. Participant is not a Canadian citizen or permanent resident, and not expected to remain in Toronto region for 12 months.
  15. Any reason in the view of the investigator.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03802461


Contacts
Layout table for location contacts
Contact: Satyender Singh, PhD 416-340-4800 ext 8353 satyender.singh@uhn.ca
Contact: Susy Hota, MD MSc FRCPC 416-340-4800 ext 7801 susy.hota@uhn.ca

Locations
Layout table for location information
Canada, Ontario
William Osler Health System Not yet recruiting
Brampton, Ontario, Canada, L6R 3J7
Sub-Investigator: David Richardson         
Joseph Brant Hospital Not yet recruiting
Burlington, Ontario, Canada, L7S 1W7
Sub-Investigator: Anne Opavsky         
Lakeridge Health Not yet recruiting
Oshawa, Ontario, Canada, L1G 2B9
Sub-Investigator: Dan Ricciuto         
MacKenzie Health Not yet recruiting
Richmond Hill, Ontario, Canada, L4C 4Z3
Sub-Investigator: Danny Chen         
The Scarborough Hospital Not yet recruiting
Scarborough, Ontario, Canada, M1P 2T7
Sub-Investigator: Reena Lovinsky         
North York General Hospital Not yet recruiting
Toronto, Ontario, Canada, M2K 1E1
Sub-Investigator: Kevin Katz         
Michael Garron Hospital Not yet recruiting
Toronto, Ontario, Canada, M4C 3E7
Sub-Investigator: Jeff Powis         
Sunnybrook Health Sciences Centre Not yet recruiting
Toronto, Ontario, Canada, M4N 3M5
Sub-Investigator: Nick Daneman         
Sub-Investigator: Jerome Leis         
St Michael's Hospital Not yet recruiting
Toronto, Ontario, Canada, M5B 1W8
Sub-Investigator: Mathew Muller         
University Health Network Recruiting
Toronto, Ontario, Canada, M5B 1W8
Principal Investigator: Susy Hota         
Public Health Ontario Laboratories Not yet recruiting
Toronto, Ontario, Canada, M5G 1M1
Sub-Investigator: Samir Patel         
Sinai Health System Recruiting
Toronto, Ontario, Canada, M5G 1X5
Sub-Investigator: Susan Poutanen         
Sub-Investigator: Allison McGeer         
Sub-Investigator: Jennie Johnstone         
St. Joseph Health Centre Not yet recruiting
Toronto, Ontario, Canada, M6R 1B5
Sub-Investigator: Mark Downing         
Sponsors and Collaborators
Susy Hota
Sinai Health System, Ontario, Canada
University of Toronto, Ontario, Canada
The Toronto Invasive Bacterial Diseases Network, Ontario, Canada
Public Health Ontario Laboratories, Ontario, Canada
Investigators
Layout table for investigator information
Principal Investigator: 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

Layout table for additonal information
Responsible Party: Susy Hota, Medical Director, Infection Prevention and Control, University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT03802461     History of Changes
Other Study ID Numbers: 18-5177
First Posted: January 14, 2019    Key Record Dates
Last Update Posted: April 1, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Susy Hota, University Health Network, Toronto:
Fecal Microbiota Transplantation
Gut Microbiome
Carbapenemase-producing Enterobacteriaceae (CPE)