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Voriconazole Versus Itraconazole In Primary Prophylaxis Of Invasive Fungal Infection (IFI) In Subjects With Allogeneic Hematopoietic Stem Cell Transplants (HSCT) (IMPROVIT)

This study has been completed.
Sponsor:
Information provided by:
Pfizer
ClinicalTrials.gov Identifier:
NCT00289991
First received: February 9, 2006
Last updated: March 26, 2010
Last verified: March 2010
  Purpose

Study is to compare antifungal prophylaxis of Voriconazole and Itraconazole in subjects who have had a Stem Cell Transplant. The success of the end point will be measured using evidence of Infection, drug compliance and survival.


Condition Intervention Phase
Antifungal Prophylaxis of Invasive Fungal Infections
Drug: Itraconazole
Drug: Vfend - voriconazole
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Prospective, Open-Label, Comparative, Multi-Center Study Of Voriconazole Compared To Itraconazole For The Primary Prophylaxis Of Invasive Fungal Infection (IFI) With Allogeneic Hematopoietic Stem Cell Transplants (HSCT)

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Success at Day 180: Percent of Responders (Randomization Strata) [ Time Frame: Day 180 (Visit 9) ] [ Designated as safety issue: No ]
    Percent of responders (by randomization strata) with success of antifungal prophylaxis at 180 days after allogeneic hematopoietic stem cell transplant (HSCT). Success: alive at Day 180 (Visit 9), had not developed a breakthrough proven or probable invasive fungal infection (IFI) by Visit 9, and received full course of study drug prophylaxis without interruption of greater than 14 days in total during the prophylaxis period; defined as failure if these criteria were not met. Additionally, if subject withdrew from study completely before Visit 9, imputed as failure at Visit 9 (programmatically).


Secondary Outcome Measures:
  • Success at Day 100: Percent of Responders (Randomization Strata) [ Time Frame: Day 100 (Visit 7) ] [ Designated as safety issue: No ]
    Percent of responders (by randomization strata) with success of antifungal prophylaxis at 100 days after allogeneic HSCT. Success defined as: alive at Day 100 (Visit 7), had not developed a breakthrough proven or probable IFI by Visit 7, and received full course of study drug prophylaxis without an interruption of >14 days in total during the prophylaxis period; defined as failure if these criteria were not met. Additionally, if subject withdrew from study completely before Visit 7, imputed as failure at Visit 7 (programmatically).

  • Time to Breakthrough Invasive Fungal Infection (IFI) [ Time Frame: Day 1 up to Day 180 (Visit 9) ] [ Designated as safety issue: No ]
    Summary of time (in days) from start of prophylaxis to first recorded occurrence of breakthrough proven or probable IFI.

  • Percent of Subjects With Occurrence of Breakthrough IFI [ Time Frame: Day 1 up to Day 100 (Visit 7) and Day 180 (Visit 9) ] [ Designated as safety issue: No ]
    Percent of subjects with occurrence of breakthrough IFI (proven or probable). Included all subjects in the MITT population.

  • Survival: Percent of Subjects Who Died at or Before Day 180 [ Time Frame: Day 1 up to Day 180 (Visit 9) ] [ Designated as safety issue: No ]
    Percent of subjects who died at or before Day 180, derived from the crude death rate. All subjects in the MITT population included in this proportion.

  • Time to Discontinuation of Study Treatment [ Time Frame: Day 1 up to Day 180 (Visit 9) ] [ Designated as safety issue: No ]
    Time in days to discontinuation of study treatment defined as the number of days from first dose to last dose inclusive as recorded in the dosing log.

  • Survival: Percent of Subjects Who Died Within 1 Year [ Time Frame: Day 1 up to 1 year (Day 365) ] [ Designated as safety issue: No ]
    Percent of subjects who died within 1 year after transplant, derived from the crude death rate. All subjects in the MITT population included in this proportion. Only deaths up until and including 365 days after first dose of study medication included in the analysis.

  • Duration of Treatment [ Time Frame: Day 1 up to Day 180 ] [ Designated as safety issue: No ]
    Median duration in days of treatment. Treatment is defined as the total number of days on which subjects took medication.

  • Percent of Subjects With Use of Other Systemic Antifungal Agents as Empirical or Therapeutic Treatment [ Time Frame: Day 1 up to Day 180 ] [ Designated as safety issue: No ]
    Percent of subjects who used other systemic antifungal agents as empirical or therapeutic treatment, defined as either empirical: subject took a systemic antifungal agent at any time after the day of first dose of medication and did not develop a breakthrough proven or probable IFI during the study or therapeutic: subject developed a breakthrough proven or probable IFI.


Enrollment: 489
Study Start Date: March 2006
Study Completion Date: February 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Itraconazole Drug: Itraconazole
Prophylaxis
Experimental: Voriconazole Drug: Vfend - voriconazole
Prophylaxis
Other Name: Vfend

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Allogeneic HSCT for acute leukemia (AML, ALL or myelodysplastic syndrome) failed lymphoma therapy or transformation of CML
  • Male and Female over 12 years or greater

Exclusion Criteria:

  • Possible, probable or proven IFI at study entry or at any time in 6 months prior to study entry, defined according to the 'consensus criteria' (Ascioglu et al 2002)
  • Previous history of zygomycosis
  • Anticipated survival less than one month
  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: NCT00289991

  Show 49 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier: NCT00289991     History of Changes
Other Study ID Numbers: A1501073
Study First Received: February 9, 2006
Results First Received: February 9, 2010
Last Updated: March 26, 2010
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Communicable Diseases
Infection
Mycoses
Hydroxyitraconazole
Itraconazole
Voriconazole
14-alpha Demethylase Inhibitors
Anti-Infective Agents
Antifungal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014