Clinical trial NCT01775397: 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
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
Overall status: TERMINATED
Phase: PHASE4
Conditions: Clostridium Difficile
Keywords: Dificid
Infections
Clostridium
Transplantation
Efficacy
Adult
Stem Cells
Fidaxomicin
Difficile
Immunosuppression
Vancomycin
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
First posted: 2013-01-25
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Sustained clinical cure of CDI at day 26
timeFrame: Day 26
Secondary outcomes:
measure: Clinical Cure of CDI
timeFrame: Day 12
measure: Sustained Clinical Cure of CDI at day 40
timeFrame: Day 40
measure: Microbial Eradication
timeFrame: Day 12
measure: Resolution of diarrhea
timeFrame: Day 12
measure: Use of further CDI therapy required
timeFrame: Between Day 10 and Day 12
measure: Number of unformed stools
timeFrame: Between Day 10 and Day 12
measure: >50% reduction in number of unformed stools compared to baseline
timeFrame: Day 1 to Day 12
measure: Recurrence of CDI
timeFrame: Between Day 1 and Day 40
measure: Time to recurrence of CDI
timeFrame: Between Day 12 and Day 40
Other outcomes:
Locations:
city: Salzburg
country: Austria
facility: Univ. Klinik für Innere Medizi
city: Herlev
country: Denmark
facility: Herlev University Hospital
city: Paris
country: France
facility: Institut Curie
city: Paris
country: France
facility: Hôpital Necker
city: Berlin
country: Germany
facility: Charité
city: Essen
country: Germany
facility: Universitätsklinikum
city: Halle
country: Germany
facility: Universitätsklinikum Halle
city: Koln
country: Germany
facility: Klinik I für Innere Medizin
city: Athens
country: Greece
facility: General Hospital of Athens
city: Athens
country: Greece
facility: Laiko General Hospital
city: Heraklion
country: Greece
facility: University Hospital of Crete
city: Piraeus
country: Greece
facility: Metaxa Anticancer Hospital
city: Brzozów
country: Poland
facility: Szpital Specjalistyczny w Brzo
city: Barcelona
country: Spain
facility: H. U. de Bellvitge
city: Madrid
country: Spain
facility: H.U. Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
Study officials:
affiliation: Astellas Pharma Europe Ltd.
name: Associate Director Medical Affairs
role: STUDY_DIRECTOR
References: