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

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)

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.

Study Overview

• Status: Completed
• Conditions: Antifungal Prophylaxis of Invasive Fungal Infections
• Intervention / Treatment: Drug: Itraconazole; Drug: Vfend - voriconazole

• Study Type: Interventional
• Enrollment (Actual): 489
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Pfizer Investigational Site
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • Pfizer Investigational Site
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • Pfizer Investigational Site
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Pfizer Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Pfizer Investigational Site
• Czech Republic
  • Bmo, Czech Republic, 625 00
    • Pfizer Investigational Site
  • Praha, Czech Republic, 128 20
    • Pfizer Investigational Site
• Egypt
  • Cairo, Egypt
    • Pfizer Investigational Site
• France
  • Caen, France, 14033
    • Pfizer Investigational Site
  • Creteil, France, 94010
    • Pfizer Investigational Site
  • Paris, France, 75475
    • Pfizer Investigational Site
  • Pessac, France, 33600
    • Pfizer Investigational Site
  • Rouen Cedex, France, 76038
    • Pfizer Investigational Site
  • Vandoeuvre Les Nancy Cedex, France, 54511
    • Pfizer Investigational Site
  • Villejuif, France, 94805
    • Pfizer Investigational Site
  • Cedex 09
    • Marseille, Cedex 09, France, 13273
      • Pfizer Investigational Site
• Greece
  • Athens, Greece, 11527
    • Pfizer Investigational Site
  • Thessaloniki
    • Exohi Asvestohoriou, Thessaloniki, Greece, 57010
      • Pfizer Investigational Site
• Jordan
  • Amman, Jordan
    • Pfizer Investigational Site
• Portugal
  • Lisboa, Portugal, 1099-023
    • Pfizer Investigational Site
  • Porto, Portugal, 4200-072
    • Pfizer Investigational Site
• Russian Federation
  • Moscow, Russian Federation, 117997
    • Pfizer Investigational Site
  • St. Petersburg, Russian Federation, 197089
    • Pfizer Investigational Site
• Spain
  • Barcelona, Spain, 08036
    • Pfizer Investigational Site
  • Barcelona, Spain, 08025
    • Pfizer Investigational Site
  • Madrid, Spain, 28034
    • Pfizer Investigational Site
  • Madrid, Spain, 28006
    • Pfizer Investigational Site
  • Madrid, Spain, 28041
    • Pfizer Investigational Site
  • Salamanca, Spain, 37007
    • Pfizer Investigational Site
  • Sevilla, Spain, 41013
    • Pfizer Investigational Site
  • Valencia, Spain, 46009
    • Pfizer Investigational Site
  • Valencia, Spain, 46010
    • Pfizer Investigational Site
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Pfizer Investigational Site
• Switzerland
  • CH-4031 Basel, Switzerland
    • Pfizer Investigational Site
  • Geneve, Switzerland, CH-1211
    • Pfizer Investigational Site
• Turkey
  • Ankara, Turkey, 06590
    • Pfizer Investigational Site
  • Kayseri, Turkey, 38039
    • Pfizer Investigational Site
• United Kingdom
  • Bristol, United Kingdom, BS2 8BL
    • Pfizer Investigational Site
  • Cambridge, United Kingdom, CB2 2QQ
    • Pfizer Investigational Site
  • Cardiff, United Kingdom, CF14 4XW
    • Pfizer Investigational Site
  • Glasgow, United Kingdom, G12 0YN
    • Pfizer Investigational Site
  • Glasgow, United Kingdom, G4 0SF
    • Pfizer Investigational Site
  • Leeds, United Kingdom, LS9-7TF
    • Pfizer Investigational Site
  • Leicester, United Kingdom, LW1 5WW
    • Pfizer Investigational Site
  • London, United Kingdom, SE5 9RS
    • Pfizer Investigational Site
  • London, United Kingdom, SE1 9RT
    • Pfizer Investigational Site
  • London, United Kingdom, NW3 2QG
    • Pfizer Investigational Site
  • Manchester, United Kingdom, M20 4BX
    • Pfizer Investigational Site
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Itraconazole	Drug: Itraconazole; Prophylaxis
Experimental: Voriconazole	Drug: Vfend - voriconazole; Prophylaxis; Other Names: Vfend

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Success at Day 180: Percent of Responders (Randomization Strata)	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).	Day 180 (Visit 9)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Success at Day 100: Percent of Responders (Randomization Strata)	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).	Day 100 (Visit 7)
Time to Breakthrough Invasive Fungal Infection (IFI)	Summary of time (in days) from start of prophylaxis to first recorded occurrence of breakthrough proven or probable IFI.	Day 1 up to Day 180 (Visit 9)
Percent of Subjects With Occurrence of Breakthrough IFI	Percent of subjects with occurrence of breakthrough IFI (proven or probable). Included all subjects in the MITT population.	Day 1 up to Day 100 (Visit 7) and Day 180 (Visit 9)
Survival: Percent of Subjects Who Died at or Before Day 180	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.	Day 1 up to Day 180 (Visit 9)
Time to Discontinuation of Study Treatment	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.	Day 1 up to Day 180 (Visit 9)
Survival: Percent of Subjects Who Died Within 1 Year	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.	Day 1 up to 1 year (Day 365)
Duration of Treatment	Median duration in days of treatment. Treatment is defined as the total number of days on which subjects took medication.	Day 1 up to Day 180
Percent of Subjects With Use of Other Systemic Antifungal Agents as Empirical or Therapeutic Treatment	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.	Day 1 up to Day 180

Collaborators and Investigators

• Sponsor: Pfizer

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Primary Completion (Actual): February 1, 2009
• Study Completion (Actual): February 1, 2009

Study Registration Dates

• First Submitted: February 9, 2006
• First Submitted That Met QC Criteria: February 9, 2006
• First Posted (Estimate): February 10, 2006

Study Record Updates

• Last Update Posted (Estimate): November 20, 2015
• Last Update Submitted That Met QC Criteria: October 16, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections and Mycoses; Infections; Communicable Diseases; Mycoses; Invasive Fungal Infections; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole; Voriconazole
• Other Study ID Numbers: A1501073