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 (FREEDOM)

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

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.

Study Overview

• Status: Terminated
• Conditions: Clostridium Difficile
• Intervention / Treatment: Drug: Placebo; Drug: Fidaxomicin; Drug: Vancomycin

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 4

Contacts and Locations

Study Locations

• Austria
  • Salzburg, Austria, 5020
    • Univ. Klinik für Innere Medizi
• Denmark
  • Herlev, Denmark, 2730
    • Herlev University Hospital
• France
  • Paris, France, 75005
    • Institut Curie
  • Paris, France, 75743
    • Hopital Necker
• Germany
  • Berlin, Germany, 10117
    • Charité
  • Essen, Germany, 45417
    • Universitätsklinikum
  • Halle, Germany, 6097
    • Universitätsklinikum Halle
  • Koln, Germany, 50937
    • Klinik I für Innere Medizin
• Greece
  • Athens, Greece, 11527
    • Laiko General Hospital
  • Athens, Greece, 10675
    • General Hospital of Athens
  • Heraklion, Greece, 70013
    • University Hospital of Crete
  • Piraeus, Greece, 18537
    • Metaxa Anticancer Hospital
• Poland
  • Brzozów, Poland, 36-200
    • Szpital Specjalistyczny w Brzo
• Spain
  • Barcelona, Spain, 08907
    • H. U. de Bellvitge
  • Madrid, Spain, 28041
    • Hospital 12 de Octubre
  • Madrid, Spain, 28007
    • H.U. Gregorio Maranon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fidaxomicin; Fidaxomicin with alternating matching placebo	Drug: Placebo; Capsule; Drug: Fidaxomicin; capsule; Other Names: Dificlir®
Active Comparator: Vancomycin; Participants received 4 doses (1 dose every 6 hours) of oral vancomycin hydrochloride each day for the duration of the 10-day treatment period	Drug: Vancomycin; capsule; Other Names: Vancocin®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Day 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Day 12
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)	Day 40
Microbial Eradication	Total viable count of clostridium difficile recovered from fecal specimen is below the limit of detection	Day 12
Resolution of diarrhea	First of two days with <3 bowel movements per day	Day 12
Use of further CDI therapy required		Between Day 10 and Day 12
Number of unformed stools		Between Day 10 and Day 12
>50% reduction in number of unformed stools compared to baseline		Day 1 to Day 12
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	Between Day 1 and Day 40
Time to recurrence of CDI	Time elapsing (days) from TOC to confirmed recurrence of CDI	Between Day 12 and Day 40

Collaborators and Investigators

• Sponsor: Astellas Pharma Europe Ltd.
• Collaborators: Cubist Pharmaceuticals LLC
• Investigators: Study Director: Associate Director Medical Affairs, Astellas Pharma Europe Ltd.

Publications and helpful links

Helpful Links

• Link to results on Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2012
• Primary Completion (Actual): April 15, 2013
• Study Completion (Actual): April 15, 2013

Study Registration Dates

• First Submitted: January 8, 2013
• First Submitted That Met QC Criteria: January 22, 2013
• First Posted (Estimate): January 25, 2013

Study Record Updates

• Last Update Posted (Actual): January 13, 2020
• Last Update Submitted That Met QC Criteria: January 8, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Immunosuppression; Efficacy; Vancomycin; Stem Cells; Adult; Transplantation; Infections; Fidaxomicin; Clostridium; Difficile; Dificid
• Additional Relevant MeSH Terms: Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Infections; Clostridium Infections; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin; Fidaxomicin
• Other Study ID Numbers: FID-EC-0001; 2012-000531-88 (EudraCT Number)