Back to resultsA Comparison of Fidaxomicin and Vancomycin in Patients With CDI Receiving Antibiotics for Concurrent Infections
Primary Purpose
Clostridium Difficile Infection (CDI)
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Fidaxomicin
Vancomycin
Sponsored by
About this trial
This is an interventional treatment trial for Clostridium Difficile Infection (CDI) focused on measuring vancomycin, fidaxomicin, CDI, diarrhea
Eligibility Criteria
Inclusion Criteria:
- Patients 18 years of age or older with >3 unformed stools/24 hours with positive stool test for C. difficile.
Patients receiving ≥ 1 high or medium risk antibiotic for treatment of an infection other than CDI, for an anticipated duration of ≥ 5 days from the time of enrollment.
- High risk: carbapenems, 2nd-4th generation cephalosporins, fluoroquinolones, clindamycin, and beta-lactam/beta-lactamase inhibitor combinations
Medium risk: 1st generation cephalosporin, macrolides*, and aztreonam
- *The macrolide would be considered to be low risk if patients are receiving intermittent macrolides for prophylaxis only and not for treatment of an acute infection
Exclusion Criteria:
- Patients with severe-complicated disease that would compromise oral therapy (hypotenstion or shock, ileus or bowel obstruction, megacolon).
- Patients with an allergy to oral vancomycin or fidaxomicin.
- Patients anticipated to receive metronidazole after enrollment.
- Patients who already received oral vancomycin or metronidazole (either oral or intravenous) for > 24 hours within the preceding 72 hours at the time of enrollment.
- Patients anticipated to receive adjunctive C. difficile therapy (rifaxamin, nitazoxanide, tigecycline) after enrollment.
Patients who are on laxatives before they are enrolled into the study, such as lactulose, if:
- Patients have had a recent dose adjustment;
- Baseline number of bowel movement while on laxatives is unknown.
- Number of bowel movements and/or consistency has not changed from baseline.
- Patients who have had colostomy or ileostomy
- Patients who will have colostomy or ileostomy after enrollment and before study ends
- Patients who are or will be on long-term (>12 weeks) medium or high-risk antibiotics prophylaxis after enrollment
Sites / Locations
- University of Michigan
- St. Joseph Mercy Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Fidaxomicin
Vancomycin
Arm Description
Fidaxomicin 200 mg PO BID for 10 days or until the end of the duration of concomitant antibiotic exposure, whichever is longer.
Vancomycin 125 mg PO QID for 10 days or until the end of the duration of concomitant antibiotic exposure, whichever is longer.
Outcomes
Primary Outcome Measures
Clinical Cure: Resolution of Diarrhea
Resolution of diarrhea defined as ≤ 3 unformed stools for 2 consecutive days maintained until the end of therapy and for 2 days afterwards. The treatment course was at least 10 days, but it could be extended to a maximum of 12 weeks.
Secondary Outcome Measures
Recurrence of CDI
Recurrence is defined as all three of the following within 4 weeks after successfully completing study treatment: reappearance of symptoms of CDI (>3 unformed stools in a 24 hour period; a positive stool PCR test for C. difficile; and the need for retreatment with an agent active against C. difficile).
30-day Mortality
Death in subjects who completed the study treatment and died within 30 days after end of treatment
Full Information
NCT ID
NCT02692651
First Posted
February 23, 2016
Last Updated
March 24, 2022
Sponsor
University of Michigan
Collaborators
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT02692651
Brief Title
A Comparison of Fidaxomicin and Vancomycin in Patients With CDI Receiving Antibiotics for Concurrent Infections
Official Title
A Comparison of Fidaxomicin and Oral Vancomycin for the Treatment of Clostridium Difficile Infection (CDI) in Hospitalized Patients Receiving Concomitant Antibiotics for the Treatment of Concurrent Systemic Infections
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
May 1, 2017 (Actual)
Primary Completion Date
May 23, 2021 (Actual)
Study Completion Date
June 23, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Michigan
Collaborators
Merck Sharp & Dohme LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Administration of concomitant antibiotics (CA) is a known risk factor for treatment failure in the treatment of CDI, as well as for recurrence of CDI. Recent data suggested that among patients receiving CA, fidaxomicin is superior to vancomycin. While these data are encouraging, many clinicians remain unclear on how to apply these data to patient care. Additionally, patients were excluded from the trials presented to the FDA if it was expected that they would require ≥ 7 days of CA. Therefore, the clinical question still remains of how to apply these data to the real world patient who requires a long course of CA and develops CDI while on therapy. We therefore propose an open label, comparative and prospective study of fidaxomicin 200 mg twice daily vs oral vancomycin 125 mg four times daily for the treatment of CDI among patients who are receiving a long course of CA.
We hypothesize that fidaxomicin will be superior to vancomycin with respect to clinical cure for patients with CDI.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clostridium Difficile Infection (CDI)
Keywords
vancomycin, fidaxomicin, CDI, diarrhea
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
144 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Fidaxomicin
Arm Type
Active Comparator
Arm Description
Fidaxomicin 200 mg PO BID for 10 days or until the end of the duration of concomitant antibiotic exposure, whichever is longer.
Arm Title
Vancomycin
Arm Type
Active Comparator
Arm Description
Vancomycin 125 mg PO QID for 10 days or until the end of the duration of concomitant antibiotic exposure, whichever is longer.
Intervention Type
Drug
Intervention Name(s)
Fidaxomicin
Other Intervention Name(s)
Dificid, Dificlir, OPT-80, PAR-101
Intervention Description
Eligible patients randomized to receive open-label Fidaxomicin will receive 200 mg twice daily for 10 days or until the end of the duration of concomitant antibiotics exposure, whichever is longer.
Intervention Type
Drug
Intervention Name(s)
Vancomycin
Other Intervention Name(s)
Vancocin
Intervention Description
Eligible patients randomized to Vancomycin will receive 125 mg orally four times daily for 10 days or until the end of the duration of concomitant antibiotics exposure, whichever is longer.
Primary Outcome Measure Information:
Title
Clinical Cure: Resolution of Diarrhea
Description
Resolution of diarrhea defined as ≤ 3 unformed stools for 2 consecutive days maintained until the end of therapy and for 2 days afterwards. The treatment course was at least 10 days, but it could be extended to a maximum of 12 weeks.
Time Frame
length of treatment plus 2 days, from a minimum of 12 to a maximum of 86 days
Secondary Outcome Measure Information:
Title
Recurrence of CDI
Description
Recurrence is defined as all three of the following within 4 weeks after successfully completing study treatment: reappearance of symptoms of CDI (>3 unformed stools in a 24 hour period; a positive stool PCR test for C. difficile; and the need for retreatment with an agent active against C. difficile).
Time Frame
30 days after treatment's end (maximum of 114 days)
Title
30-day Mortality
Description
Death in subjects who completed the study treatment and died within 30 days after end of treatment
Time Frame
40 to 114 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients 18 years of age or older with >3 unformed stools/24 hours with positive stool test for C. difficile.
Patients receiving ≥ 1 high or medium risk antibiotic for treatment of an infection other than CDI, for an anticipated duration of ≥ 5 days from the time of enrollment.
High risk: carbapenems, 2nd-4th generation cephalosporins, fluoroquinolones, clindamycin, and beta-lactam/beta-lactamase inhibitor combinations
Medium risk: 1st generation cephalosporin, macrolides*, and aztreonam
*The macrolide would be considered to be low risk if patients are receiving intermittent macrolides for prophylaxis only and not for treatment of an acute infection
Exclusion Criteria:
Patients with severe-complicated disease that would compromise oral therapy (hypotenstion or shock, ileus or bowel obstruction, megacolon).
Patients with an allergy to oral vancomycin or fidaxomicin.
Patients anticipated to receive metronidazole after enrollment.
Patients who already received oral vancomycin or metronidazole (either oral or intravenous) for > 24 hours within the preceding 72 hours at the time of enrollment.
Patients anticipated to receive adjunctive C. difficile therapy (rifaxamin, nitazoxanide, tigecycline) after enrollment.
Patients who are on laxatives before they are enrolled into the study, such as lactulose, if:
Patients have had a recent dose adjustment;
Baseline number of bowel movement while on laxatives is unknown.
Number of bowel movements and/or consistency has not changed from baseline.
Patients who have had colostomy or ileostomy
Patients who will have colostomy or ileostomy after enrollment and before study ends
Patients who are or will be on long-term (>12 weeks) medium or high-risk antibiotics prophylaxis after enrollment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
A. Krishna Rao, MD, MS
Organizational Affiliation
University of Michigan
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
St. Joseph Mercy Hospital
City
Ypsilanti
State/Province
Michigan
ZIP/Postal Code
48197
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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A Comparison of Fidaxomicin and Vancomycin in Patients With CDI Receiving Antibiotics for Concurrent Infections
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