Back to resultsA Post-marketing, Blinded Study to Investigate How Effective Fidaxomicin is Compared to Vancomycin in the Sustained Cure of Clostridium Difficile Infection in Adults That Are Receiving Therapy to Suppress the Immune System (FREEDOM)
Primary Purpose
Clostridium Difficile
Status
Terminated
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Fidaxomicin
Vancomycin
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Clostridium Difficile focused on measuring Dificid, Infections, Clostridium, Transplantation, Efficacy, Adult, Stem Cells, Fidaxomicin, Difficile, Immunosuppression, Vancomycin
Eligibility Criteria
Inclusion Criteria:
- CDI is confirmed by clinical symptoms and rapid CDI test
- Subject has not been treated with medication for CDI within the last 10 days
Subject is:
- receiving immunosuppressive therapy (chemotherapy) or is undergoing a stem cell transplant procedure (defined as the time period from the start of conditioning prior to transplant until 6 months after infusion of stem cells) for a hematological malignancy; or
- receiving immunosuppressive therapy (chemotherapy) for a solid tumor malignancy or following solid organ transplantation; or
- being treated with immunosuppressive and /or anti-TNF therapy for an auto-immune disease
- Any woman of childbearing potential requires negative serum or urine pregnancy test before entry to the study
- Male and female subjects that are sexually active must agree to practice effective birth control during the study and for 30 days after the end of the study
Exclusion Criteria:
- The subject has experienced more than one previous episode of CDI within the 3 months prior to study inclusion
- Taking or requiring to be treated with prohibited medications
- Unable to take oral study medication
- Female patients that are pregnant, intend to become pregnant or are breastfeeding
- History of ulcerative colitis or Crohn's disease
- History or diagnosis of toxic megacolon or pseudomembranous colitis
- Hypersensitivity to fidaxomicin or any of its components
- Hypersensitivity to vancomycin or any of its components
Sites / Locations
- Univ. Klinik für Innere Medizi
- Herlev University Hospital
- Institut Curie
- Hôpital Necker
- Charité
- Universitätsklinikum
- Universitätsklinikum Halle
- Klinik I für Innere Medizin
- General Hospital of Athens
- Laiko General Hospital
- University Hospital of Crete
- Metaxa Anticancer Hospital
- Szpital Specjalistyczny w Brzo
- H. U. de Bellvitge
- H.U. Gregorio Maranon
- Hospital 12 de Octubre
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Fidaxomicin
Vancomycin
Arm Description
Fidaxomicin with alternating matching placebo
Participants received 4 doses (1 dose every 6 hours) of oral vancomycin hydrochloride each day for the duration of the 10-day treatment period
Outcomes
Primary Outcome Measures
Sustained clinical cure of CDI at day 26
Clinical cure is defined as a subject that at TOC no further CDI therapy is required since completion of study medication, and has either:
≤3 unformed bowel movements for two consecutive days
≥50% reduction in the number of unformed bowel movements compared to baseline; or
75% reduction in the volume of liquid stool collected or no longer passing liquid stools (for subjects having rectal collection device)
Secondary Outcome Measures
Clinical Cure of CDI
Clinical cure is defined as a subject that at TOC no further CDI therapy is required since completion of study medication, and has either:
≤3 unformed bowel movements for two consecutive days
≥50% reduction in the number of unformed bowel movements compared to baseline; or
75% reduction in the volume of liquid stool collected or no longer passing liquid stools (for subjects having rectal collection device)
Sustained Clinical Cure of CDI at day 40
Clinical cure is defined as a subject that at TOC no further CDI therapy is required since completion of study medication, and has either:
≤3 unformed bowel movements for two consecutive days
≥50% reduction in the number of unformed bowel movements compared to baseline; or
75% reduction in the volume of liquid stool collected or no longer passing liquid stools (for subjects having rectal collection device)
Microbial Eradication
Total viable count of clostridium difficile recovered from fecal specimen is below the limit of detection
Resolution of diarrhea
First of two days with <3 bowel movements per day
Use of further CDI therapy required
Number of unformed stools
>50% reduction in number of unformed stools compared to baseline
Recurrence of CDI
After TOC, re-establishment of diarrhea to an extent that is greater than the frequency recorded on the last day of study medication
Time to recurrence of CDI
Time elapsing (days) from TOC to confirmed recurrence of CDI
Full Information
NCT ID
NCT01775397
First Posted
January 8, 2013
Last Updated
January 8, 2020
Sponsor
Astellas Pharma Europe Ltd.
Collaborators
Cubist Pharmaceuticals LLC
1. Study Identification
Unique Protocol Identification Number
NCT01775397
Brief Title
A Post-marketing, Blinded Study to Investigate How Effective Fidaxomicin is Compared to Vancomycin in the Sustained Cure of Clostridium Difficile Infection in Adults That Are Receiving Therapy to Suppress the Immune System
Acronym
FREEDOM
Official Title
A Phase IIIb/IV Randomized, Controlled, Double-blind, Double-dummy, Parallel Group Study to Compare the Efficacy of Fidaxomicin to Vancomycin in the Sustained Clinical Cure of Clostridium Difficile Infection in Adults Receiving Immunosuppressive Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Terminated
Why Stopped
Study terminated due to difficulty in enrollment
Study Start Date
November 29, 2012 (Actual)
Primary Completion Date
April 15, 2013 (Actual)
Study Completion Date
April 15, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Astellas Pharma Europe Ltd.
Collaborators
Cubist Pharmaceuticals LLC
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary objective is to compare fidaxomicin versus vancomycin for the sustained clinical cure of Clostridium difficile Infection (CDI) in adult patients receiving immunosuppressive therapy.
Detailed Description
On Day 1, subjects with diarrhea defined as having three or more unformed bowel movements or >200 mL of unformed stool (for subjects having rectal collection devices) within 24 hours, confirmed by a rapid CDI test (positive for both toxins A & B and glutamate dehydrogenase) to have CDI will be randomized to receive fidaxomicin or vancomycin (1:1 randomization).
Subjects will be treated with study medication from Day 1 to Day 10. Assessment for clinical cure (Test of Cure [TOC]) will take place 48 - 72 hours after End of Treatment (EOT). Subjects not meeting the definition of clinical cure at TOC will be defined as treatment failures.
A stool sample for evaluation of microbial cure will be taken at TOC on Day 12.
Subjects meeting the criteria for clinical cure at TOC will be monitored for recurrence until 28 days after TOC (Day 40).
Treatment of subjects with recurrence of CDI will be at the
discretion of the Investigator.
Subjects not meeting the criteria for clinical cure at TOC will be followed for safety until Day 40. Further CDI treatment will be at the discretion of the Investigator.
The strain of Clostridium difficile will be determined for all samples.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clostridium Difficile
Keywords
Dificid, Infections, Clostridium, Transplantation, Efficacy, Adult, Stem Cells, Fidaxomicin, Difficile, Immunosuppression, Vancomycin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Fidaxomicin
Arm Type
Experimental
Arm Description
Fidaxomicin with alternating matching placebo
Arm Title
Vancomycin
Arm Type
Active Comparator
Arm Description
Participants received 4 doses (1 dose every 6 hours) of oral vancomycin hydrochloride each day for the duration of the 10-day treatment period
Intervention Type
Drug
Intervention Name(s)
Fidaxomicin
Other Intervention Name(s)
Dificlir®
Intervention Description
capsule
Intervention Type
Drug
Intervention Name(s)
Vancomycin
Other Intervention Name(s)
Vancocin®
Intervention Description
capsule
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Capsule
Primary Outcome Measure Information:
Title
Sustained clinical cure of CDI at day 26
Description
Clinical cure is defined as a subject that at TOC no further CDI therapy is required since completion of study medication, and has either:
≤3 unformed bowel movements for two consecutive days
≥50% reduction in the number of unformed bowel movements compared to baseline; or
75% reduction in the volume of liquid stool collected or no longer passing liquid stools (for subjects having rectal collection device)
Time Frame
Day 26
Secondary Outcome Measure Information:
Title
Clinical Cure of CDI
Description
Clinical cure is defined as a subject that at TOC no further CDI therapy is required since completion of study medication, and has either:
≤3 unformed bowel movements for two consecutive days
≥50% reduction in the number of unformed bowel movements compared to baseline; or
75% reduction in the volume of liquid stool collected or no longer passing liquid stools (for subjects having rectal collection device)
Time Frame
Day 12
Title
Sustained Clinical Cure of CDI at day 40
Description
Clinical cure is defined as a subject that at TOC no further CDI therapy is required since completion of study medication, and has either:
≤3 unformed bowel movements for two consecutive days
≥50% reduction in the number of unformed bowel movements compared to baseline; or
75% reduction in the volume of liquid stool collected or no longer passing liquid stools (for subjects having rectal collection device)
Time Frame
Day 40
Title
Microbial Eradication
Description
Total viable count of clostridium difficile recovered from fecal specimen is below the limit of detection
Time Frame
Day 12
Title
Resolution of diarrhea
Description
First of two days with <3 bowel movements per day
Time Frame
Day 12
Title
Use of further CDI therapy required
Time Frame
Between Day 10 and Day 12
Title
Number of unformed stools
Time Frame
Between Day 10 and Day 12
Title
>50% reduction in number of unformed stools compared to baseline
Time Frame
Day 1 to Day 12
Title
Recurrence of CDI
Description
After TOC, re-establishment of diarrhea to an extent that is greater than the frequency recorded on the last day of study medication
Time Frame
Between Day 1 and Day 40
Title
Time to recurrence of CDI
Description
Time elapsing (days) from TOC to confirmed recurrence of CDI
Time Frame
Between Day 12 and Day 40
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
CDI is confirmed by clinical symptoms and rapid CDI test
Subject has not been treated with medication for CDI within the last 10 days
Subject is:
receiving immunosuppressive therapy (chemotherapy) or is undergoing a stem cell transplant procedure (defined as the time period from the start of conditioning prior to transplant until 6 months after infusion of stem cells) for a hematological malignancy; or
receiving immunosuppressive therapy (chemotherapy) for a solid tumor malignancy or following solid organ transplantation; or
being treated with immunosuppressive and /or anti-TNF therapy for an auto-immune disease
Any woman of childbearing potential requires negative serum or urine pregnancy test before entry to the study
Male and female subjects that are sexually active must agree to practice effective birth control during the study and for 30 days after the end of the study
Exclusion Criteria:
The subject has experienced more than one previous episode of CDI within the 3 months prior to study inclusion
Taking or requiring to be treated with prohibited medications
Unable to take oral study medication
Female patients that are pregnant, intend to become pregnant or are breastfeeding
History of ulcerative colitis or Crohn's disease
History or diagnosis of toxic megacolon or pseudomembranous colitis
Hypersensitivity to fidaxomicin or any of its components
Hypersensitivity to vancomycin or any of its components
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Associate Director Medical Affairs
Organizational Affiliation
Astellas Pharma Europe Ltd.
Official's Role
Study Director
Facility Information:
Facility Name
Univ. Klinik für Innere Medizi
City
Salzburg
ZIP/Postal Code
5020
Country
Austria
Facility Name
Herlev University Hospital
City
Herlev
ZIP/Postal Code
2730
Country
Denmark
Facility Name
Institut Curie
City
Paris
ZIP/Postal Code
75005
Country
France
Facility Name
Hôpital Necker
City
Paris
ZIP/Postal Code
75743
Country
France
Facility Name
Charité
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Universitätsklinikum
City
Essen
ZIP/Postal Code
45417
Country
Germany
Facility Name
Universitätsklinikum Halle
City
Halle
ZIP/Postal Code
6097
Country
Germany
Facility Name
Klinik I für Innere Medizin
City
Koln
ZIP/Postal Code
50937
Country
Germany
Facility Name
General Hospital of Athens
City
Athens
ZIP/Postal Code
10675
Country
Greece
Facility Name
Laiko General Hospital
City
Athens
ZIP/Postal Code
11527
Country
Greece
Facility Name
University Hospital of Crete
City
Heraklion
ZIP/Postal Code
70013
Country
Greece
Facility Name
Metaxa Anticancer Hospital
City
Piraeus
ZIP/Postal Code
18537
Country
Greece
Facility Name
Szpital Specjalistyczny w Brzo
City
Brzozów
ZIP/Postal Code
36-200
Country
Poland
Facility Name
H. U. de Bellvitge
City
Barcelona
ZIP/Postal Code
08907
Country
Spain
Facility Name
H.U. Gregorio Maranon
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Hospital 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
12. IPD Sharing Statement
Links:
URL
https://astellasclinicalstudyresults.com/study.aspx?ID=345
Description
Link to results on Astellas Clinical Study Results website
Learn more about this trial
A Post-marketing, Blinded Study to Investigate How Effective Fidaxomicin is Compared to Vancomycin in the Sustained Cure of Clostridium Difficile Infection in Adults That Are Receiving Therapy to Suppress the Immune System
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