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FMT Versus Antimicrobials for Initial Treatment of Recurrent CDI

Primary Purpose

Clostridium Difficile Infection

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
FMT
Antimicrobials
Sponsored by
NorthShore University HealthSystem
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Clostridium Difficile Infection focused on measuring CDI, C difficile, C diff, Clostridium difficile

Eligibility Criteria

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

Inclusion Criteria:

  • Diagnosis of active C. difficile infection, defined as > 3 diarrheal stools per day and a positive C. difficile PCR assay
  • Hospitalized patient presenting with first relapse of CDI occuring between 15 and 90 days after an index episode of CDI

Exclusion Criteria:

  • Pregnancy
  • Neutropenia (absolute neutrophil count <1000/microliters)
  • Contraindication for retention enema
  • Food allergy not controlled in the donor diet

Sites / Locations

  • NorthShore University HealthSystem

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

FMT Group (Intervention Arm)

Antimicrobial Group (Control Arm)

Arm Description

Patients randomized to the FMT group will have antimicrobials targeting C. difficile discontinued at least 6 hours prior to undergoing an FMT via retention enema. A second FMT via retention enema will be administered at 24 hours if diarrhea persists.

Patients randomized to the antimicrobial group will be treated with antibiotics targeting C. difficile according to the Society for Healthcare Epidemiology of America (SHEA) Clinical Practice Guidelines for CDI. FMT will be offered to this group after 90 days if they experience relapsing CDI.

Outcomes

Primary Outcome Measures

Number of Patients With Clinical Resolution of Diarrhea
Number of patients with resolution of diarrhea and other abdominal symptoms or return to baseline symptoms that were present prior to C. difficile diagnosis

Secondary Outcome Measures

Time to Clinical Resolution of Symptoms
Amount of time it takes for patient to have cessation of diarrhea and abdominal pain/gastrointestinal symptoms (or return to baseline) and normalization of white blood cell count, creatinine, and temperature.
Hospital Length of Stay
Patients' length of stay post-procedure will be measured
Number of Patients With Hospital Readmission
Number of patients re-admitted to the hospital for recurrent Clostridium difficile infection
Mortality
Number of patients who died from any cause within 90 days of randomization

Full Information

First Posted
September 30, 2014
Last Updated
February 1, 2023
Sponsor
NorthShore University HealthSystem
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1. Study Identification

Unique Protocol Identification Number
NCT02255305
Brief Title
FMT Versus Antimicrobials for Initial Treatment of Recurrent CDI
Official Title
Fecal Microbiota Transplantation Versus Standard Medical Therapy for Initial Treatment of Recurrent Clostridium Difficile Infection
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Terminated
Why Stopped
Due to personnel issues for finding and enrolling patients, performing appropriate follow-up and performing FMT procedure
Study Start Date
January 2015 (undefined)
Primary Completion Date
January 2020 (Actual)
Study Completion Date
January 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
NorthShore University HealthSystem

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of the study is to determine the safety and efficacy of Fecal Microbiota Transplant (FMT) for the treatment of the recurrence of Clostridium difficile infection (CDI) as compared to standard antibiotic therapy. Patients who have tested positive for CDI within 90 days of an admission for relapse of CDI will be approached to participate in this open-label, randomized controlled trial. Patients will either be randomized to the intervention group (receive FMT via retention enema) or the control group (receive antimicrobials targeting CDI).
Detailed Description
This trial is an open-label, randomized, controlled trial evaluating the safety and efficacy of fecal microbiota transplantation (FMT) for the treatment of the recurrence of Clostridium difficile infection (CDI) as compared to standard antibiotic therapy. Clostridium difficile infection (CDI) has increased in incidence and severity over the last decade and is associated with poor outcomes including increased morbidity, mortality, and healthcare costs (1-8). Relapse occurs in 15-35% of patients after the first episode of CDI and 45-65% of patients who have one relapse will experience a subsequent relapse (9, 10). Dysbiosis - decreased diversity of the fecal microbiome - is thought to contribute to the high rate of relapse (11). FMT quickly and successfully restores normal intestinal microorganisms of the diseased patient via infusion of a liquid stool preparation from a healthy donor. FMT resulted in disease resolution in ~90% of cases reported in a systematic review and meta-analyses without any significant adverse events noted (12, 13). All hospitalized patients in the NorthShore system >18 years of age who are diagnosed with active CDI, defined as >3 diarrheal stools per day and a positive C. difficile polymerase chain reaction (PCR) assay, will be evaluated for inclusion in the study. Hospitalized patients presenting with their first or greater relapse of CDI occurring between 15 and 90 days after an index episode of CDI will be eligible for enrollment. Exclusion criteria will include pregnancy, neutropenia (absolute neutrophil count <1000/μl), contraindication for retention enema, or food allergy not controlled for in the donor diet. Eligible patients will undergo written informed consent followed by randomization into intervention and control groups. Patients who are randomized to the intervention group will have antimicrobials targeting C. difficile discontinued at least 6 hours prior to undergoing an FMT via retention enema. A second FMT via retention enema will be administered at 24 hours if diarrhea persists. Patients randomized to the control group will be treated with antimicrobials targeting C. difficile according to the Society for Healthcare Epidemiology of America Clinical Practice Guidelines for CDI (18). FMT will be offered to the control group after 90 days if they experience relapsing CDI. Two healthy "universal" donors who have previously donated fecal material for FMT have expressed willingness to participate in the study. Donors will complete the American Association of Blood Banks donor questionnaire for exposure to infectious agents as well as undergo serologic and stool testing for communicable diseases or pathogenic bacteria/viruses as previously described (17).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clostridium Difficile Infection
Keywords
CDI, C difficile, C diff, Clostridium difficile

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
FMT Group (Intervention Arm)
Arm Type
Experimental
Arm Description
Patients randomized to the FMT group will have antimicrobials targeting C. difficile discontinued at least 6 hours prior to undergoing an FMT via retention enema. A second FMT via retention enema will be administered at 24 hours if diarrhea persists.
Arm Title
Antimicrobial Group (Control Arm)
Arm Type
Active Comparator
Arm Description
Patients randomized to the antimicrobial group will be treated with antibiotics targeting C. difficile according to the Society for Healthcare Epidemiology of America (SHEA) Clinical Practice Guidelines for CDI. FMT will be offered to this group after 90 days if they experience relapsing CDI.
Intervention Type
Biological
Intervention Name(s)
FMT
Other Intervention Name(s)
Fecal Microbiota Transplant, Stool Transplant
Intervention Description
Patients in the FMT group will receive ~50 grams of fecal material suspended in bacteriostatic normal saline and glycerol.
Intervention Type
Drug
Intervention Name(s)
Antimicrobials
Intervention Description
Patients randomized to the control group will receive antimicrobials targeting C. difficile.
Primary Outcome Measure Information:
Title
Number of Patients With Clinical Resolution of Diarrhea
Description
Number of patients with resolution of diarrhea and other abdominal symptoms or return to baseline symptoms that were present prior to C. difficile diagnosis
Time Frame
90 days
Secondary Outcome Measure Information:
Title
Time to Clinical Resolution of Symptoms
Description
Amount of time it takes for patient to have cessation of diarrhea and abdominal pain/gastrointestinal symptoms (or return to baseline) and normalization of white blood cell count, creatinine, and temperature.
Time Frame
90 days
Title
Hospital Length of Stay
Description
Patients' length of stay post-procedure will be measured
Time Frame
90 days
Title
Number of Patients With Hospital Readmission
Description
Number of patients re-admitted to the hospital for recurrent Clostridium difficile infection
Time Frame
90 days
Title
Mortality
Description
Number of patients who died from any cause within 90 days of randomization
Time Frame
90 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of active C. difficile infection, defined as > 3 diarrheal stools per day and a positive C. difficile PCR assay Hospitalized patient presenting with first relapse of CDI occuring between 15 and 90 days after an index episode of CDI Exclusion Criteria: Pregnancy Neutropenia (absolute neutrophil count <1000/microliters) Contraindication for retention enema Food allergy not controlled in the donor diet
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Becky Smith, MD
Organizational Affiliation
NorthShore University HealthSystem
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jennifer Grant, MD
Organizational Affiliation
NorthShore University HealthSystem
Official's Role
Principal Investigator
Facility Information:
Facility Name
NorthShore University HealthSystem
City
Evanston
State/Province
Illinois
ZIP/Postal Code
60201
Country
United States

12. IPD Sharing Statement

Citations:
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11882758
Citation
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FMT Versus Antimicrobials for Initial Treatment of Recurrent CDI

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