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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Antifungal Prophylaxis of Invasive Fungal Infections

Intervention / Treatment
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* Drug: Itraconazole
* Drug: Vfend - voriconazole


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Itraconazole<br> | Drug: Itraconazole<br>* Prophylaxis<br>|
| Experimental: Voriconazole<br> | Drug: Vfend - voriconazole<br>* Prophylaxis<br>* Other names: Vfend;|

What is the study measuring?
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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 |