Design issues in a prospective randomized double-blinded trial of prophylaxis with fluconazole versus voriconazole
1Department of Medicine, Blood and Marrow Transplant Program, Division of Hematology/Oncology, University of Florida Shands Cancer Center, Gainesville, FL 32610, USA. wingajr@medicine.ufl.edu
Background:
Aspergillus infections pose the toughest infectious challenges to the clinician caring for hematopoietic cell transplant recipients. About 15% of patients become infected, with a case fatality rate of approximately 65%. To date, no effective prophylactic strategies have been developed.
Methods:
Voriconazole, a recently licensed extended-spectrum azole, with demonstrated efficacy against aspergillus, is currently being tested as a potential prophylactic agent against aspergillus and other invasive fungal infections. Logistic issues--such as patient selection, choice of comparator, blinding of study drugs, duration of study drug administration, and how to handle empirical amphotericin B for possible invasive fungal infections--and analytic concerns, including choice and definition of the primary end point and the potential confounding effect of informative censoring (as a result of noninfectious events), were considered in the design of the clinical trial.
Results:
The trial is now under way, with a projected 3-year enrollment period.
Conclusions:
Each design decision shaped the trial in a way that permitted certain questions to be answered while not allowing others to be addressed. Once completed, the trial's results must be interpreted in light of these design details.
Insights
A clinical trial is evaluating voriconazole as a prophylactic agent for Aspergillus infections in hematopoietic cell transplant recipients. This study aims to address critical challenges in preventing these severe fungal infections.
Area of Science:
- Mycology
- Infectious Diseases
- Hematology
Background:
- Aspergillus infections present significant challenges in hematopoietic cell transplant (HCT) recipients.
- These infections occur in approximately 15% of HCT patients, with a high case fatality rate of around 65%.
- Currently, no effective prophylactic strategies exist for preventing Aspergillus infections in this vulnerable population.
Purpose of the Study:
- To evaluate voriconazole, an extended-spectrum azole, as a prophylactic agent against Aspergillus and other invasive fungal infections in HCT recipients.
- To address logistical and analytical challenges in designing a clinical trial for antifungal prophylaxis.
Main Methods:
- A clinical trial is investigating the use of voriconazole for prophylaxis.
- Key design considerations included patient selection, comparator choice, blinding, drug administration duration, and management of empirical treatments.
- Analytic concerns such as endpoint definition and informative censoring were also addressed.
Main Results:
- The clinical trial is currently active with a projected 3-year enrollment period.
- Specific results regarding voriconazole's efficacy are pending trial completion.
Conclusions:
- The trial's design incorporates specific decisions to address certain research questions.
- Interpretation of the trial's results will require careful consideration of these design elements upon completion.
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