Antifungal Prophylaxis of Invasive Fungal Infections Clinical Trial
— IMPROVITOfficial 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)
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.
| Status | Completed |
| Enrollment | 489 |
| Est. completion date | February 2009 |
| Est. primary completion date | February 2009 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 12 Years and older |
| Eligibility |
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 |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
| Country | Name | City | State |
|---|---|---|---|
| Canada | Pfizer Investigational Site | Hamilton | Ontario |
| Canada | Pfizer Investigational Site | Montreal | Quebec |
| Canada | Pfizer Investigational Site | Vancouver | British Columbia |
| Canada | Pfizer Investigational Site | Winnipeg | Manitoba |
| Canada | Pfizer Investigational Site | Winnipeg | Manitoba |
| Czech Republic | Pfizer Investigational Site | Bmo | |
| Czech Republic | Pfizer Investigational Site | Praha | |
| Egypt | Pfizer Investigational Site | Cairo | |
| France | Pfizer Investigational Site | Caen | |
| France | Pfizer Investigational Site | Creteil | |
| France | Pfizer Investigational Site | Marseille | Cedex 09 |
| France | Pfizer Investigational Site | Paris | |
| France | Pfizer Investigational Site | Pessac | |
| France | Pfizer Investigational Site | Rouen Cedex | |
| France | Pfizer Investigational Site | Vandoeuvre Les Nancy Cedex | |
| France | Pfizer Investigational Site | Villejuif | |
| Greece | Pfizer Investigational Site | Athens | |
| Greece | Pfizer Investigational Site | Exohi Asvestohoriou | Thessaloniki |
| Jordan | Pfizer Investigational Site | Amman | |
| Portugal | Pfizer Investigational Site | Lisboa | |
| Portugal | Pfizer Investigational Site | Porto | |
| Russian Federation | Pfizer Investigational Site | Moscow | |
| Russian Federation | Pfizer Investigational Site | St. Petersburg | |
| Spain | Pfizer Investigational Site | Badalona | Barcelona |
| Spain | Pfizer Investigational Site | Barcelona | |
| Spain | Pfizer Investigational Site | Barcelona | |
| Spain | Pfizer Investigational Site | Madrid | |
| Spain | Pfizer Investigational Site | Madrid | |
| Spain | Pfizer Investigational Site | Madrid | |
| Spain | Pfizer Investigational Site | Salamanca | |
| Spain | Pfizer Investigational Site | Sevilla | |
| Spain | Pfizer Investigational Site | Valencia | |
| Spain | Pfizer Investigational Site | Valencia | |
| Switzerland | Pfizer Investigational Site | CH-4031 Basel | |
| Switzerland | Pfizer Investigational Site | Geneve | |
| Turkey | Pfizer Investigational Site | Ankara | |
| Turkey | Pfizer Investigational Site | Kayseri | |
| United Kingdom | Pfizer Investigational Site | Bristol | |
| United Kingdom | Pfizer Investigational Site | Cambridge | |
| United Kingdom | Pfizer Investigational Site | Cardiff | |
| United Kingdom | Pfizer Investigational Site | Glasgow | |
| United Kingdom | Pfizer Investigational Site | Glasgow | |
| United Kingdom | Pfizer Investigational Site | Leeds | |
| United Kingdom | Pfizer Investigational Site | Leicester | |
| United Kingdom | Pfizer Investigational Site | London | |
| United Kingdom | Pfizer Investigational Site | London | |
| United Kingdom | Pfizer Investigational Site | London | |
| United Kingdom | Pfizer Investigational Site | Manchester | |
| United Kingdom | Pfizer Investigational Site | Sutton | Surrey |
| Lead Sponsor | Collaborator |
|---|---|
| Pfizer |
Canada, Czech Republic, Egypt, France, Greece, Jordan, Portugal, Russian Federation, Spain, Switzerland, Turkey, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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) | No |
| Secondary | 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) | No |
| Secondary | 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) | No |
| Secondary | 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) | No |
| Secondary | 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) | No |
| Secondary | 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) | No |
| Secondary | 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) | No |
| Secondary | 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 | No |
| Secondary | 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 | No |