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)

This study has been terminated.
(Study terminated due to difficulty in enrollment)
Sponsor:
Collaborator:
Cubist Pharmaceuticals
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Europe Ltd. )
ClinicalTrials.gov Identifier:
NCT01775397
First received: January 8, 2013
Last updated: June 2, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Clostridium Difficile
Drug: Fidaxomicin
Drug: Vancomycin
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Sustained clinical cure of CDI at day 26 [ Time Frame: Day 26 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Day 12 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Day 40 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Day 12 ] [ Designated as safety issue: No ]
    Total viable count of clostridium difficile recovered from fecal specimen is below the limit of detection

  • Resolution of diarrhea [ Time Frame: Day 12 ] [ Designated as safety issue: No ]
    First of two days with <3 bowel movements per day

  • Use of further CDI therapy required [ Time Frame: Between Day 10 and Day 12 ] [ Designated as safety issue: No ]
  • Number of unformed stools [ Time Frame: Between Day 10 and Day 12 ] [ Designated as safety issue: No ]
  • >50% reduction in number of unformed stools compared to baseline [ Time Frame: Day 1 to Day 12 ] [ Designated as safety issue: No ]
  • Recurrence of CDI [ Time Frame: Between Day 1 and Day 40 ] [ Designated as safety issue: No ]
    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 Frame: Between Day 12 and Day 40 ] [ Designated as safety issue: No ]
    Time elapsing (days) from TOC to confirmed recurrence of CDI


Enrollment: 12
Study Start Date: November 2012
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fidaxomicin
Fidaxomicin with alternating matching placebo
Drug: Fidaxomicin
capsule
Other Name: Dificlir®
Drug: Placebo
Capsule
Active Comparator: Vancomycin Drug: Vancomycin
capsule
Other Name: Vancocin®

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01775397

Locations
Austria
Univ. Klinik für Innere Medizi
Salzburg, Austria, 5020
Denmark
Herlev University Hospital
Herlev, Denmark, 2730
France
Hôpital Necker
Paris, France, 75743
Institut Curie
Paris, France, 75005
Germany
Charité
Berlin, Germany, 10117
Universitätsklinikum
Essen, Germany, 45417
Universitätsklinikum Halle
Halle, Germany, 6097
Klinik I für Innere Medizin
Koln, Germany, 50937
Greece
Laiko General Hospital
Athens, Greece, 11527
General Hospital of Athens
Athens, Greece, 10675
University Hospital of Crete
Heraklion, Greece, 70013
Metaxa Anticancer Hospital
Piraeus, Greece, 18537
Poland
Szpital Specjalistyczny w Brzo
Brzozów, Poland, 36-200
Spain
H. U. de Bellvitge
Barcelona, Spain, 08907
H.U. Gregorio Maranon
Madrid, Spain, 28007
Hospital 12 de Octubre
Madrid, Spain, 28041
Sponsors and Collaborators
Astellas Pharma Europe Ltd.
Cubist Pharmaceuticals
Investigators
Study Director: Associate Director Medical Affairs Astellas Pharma Europe Ltd.
  More Information

Additional Information:
No publications provided

Responsible Party: Astellas Pharma Inc ( Astellas Pharma Europe Ltd. )
ClinicalTrials.gov Identifier: NCT01775397     History of Changes
Other Study ID Numbers: FID-EC-0001, 2012-000531-88
Study First Received: January 8, 2013
Last Updated: June 2, 2014
Health Authority: Austria: Federal Office for Safety in Health Care
Denmark: Danish Medicines Agency
Finland: Finnish Medicines Agency
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
Hungary: National Institute of Pharmacy
Italy: The Italian Medicines Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Russia: Ministry of Health of the Russian Federation
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Astellas Pharma Inc:
Clostridium
Difficile
Infections
Immunosuppression
Fidaxomicin
Vancomycin
Efficacy
Stem Cells
Transplantation
Adult
Dificid

Additional relevant MeSH terms:
Infection
Vancomycin
Anti-Bacterial Agents
Anti-Infective Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014