Voriconazole Trough Plasma Levels : Genetic Polymorphism, Efficacy, Safety in Patients With Hematologic Malignancy
|ClinicalTrials.gov Identifier: NCT01148160|
Recruitment Status : Terminated
First Posted : June 22, 2010
Last Update Posted : April 10, 2014
Multiple factors are associated with a large variability in voriconazole exposure following standard dose administration, such as non-linear saturable pharmacokinetics, drug-drug interactions, liver disease, patient age, and genetic polymorphism of the metabolic enzymes.
Voriconazole is extensively metabolized by the human hepatic enzymes, primarily mediated by CYP2C19. The polymorphisms account for a relatively large portion of inter-individual variance observed in voriconazole plasma concentrations.
However, there are limited data on the relationships between voriconazole blood levels and clinical outcomes or safety in Asian populations.
The purpose of this study is to investigate the relationships of voriconazole blood levels with genetic polymorphism, safety, and clinical outcomes in immunocompromised patients with invasive pulmonary aspergillosis.
|Condition or disease||Intervention/treatment|
|Invasive Fungal Infection||Drug: voriconazole|
The investigators are trying to establish that routine clinical practice for voriconazole therapeutic drug monitoring can improve the efficacy and safety outcomes.
In Korean patients with hematologic malignancy, the investigators also want to propose the optimal dosing guideline of voriconazole with different genetic polymorphisms.
|Study Type :||Observational|
|Actual Enrollment :||10 participants|
|Official Title:||The Correlation of Voriconazole Trough Plasma Levels With Genetic Polymorphism, Efficacy, and Safety Outcomes in Hematologic Malignancy Patients With Invasive Pulmonary Aspergillosis|
|Study Start Date :||August 2010|
|Actual Primary Completion Date :||April 2014|
|Actual Study Completion Date :||April 2014|
Patients with hematologic malignancies who were given voriconazole to treat invasive (pulmonary) aspergillosis at Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
intravenous, oral administration
- Successful outcome at 12 weeks after voriconazole use [ Time Frame: 12 weeks ]Successful outcome = complete response + partial response Unsuccessful outcome = stable disease + failure of therapy + indeterminate response
- IFI (invasive fungal infection)-related mortality at 12 weeks [ Time Frame: 12 weeks ]IFI (invasive fungal infection)-related mortality at 12 weeks
- Successful outcomes at various time points [ Time Frame: 1 week, 2 weeks, 4 weeks, and 8 weeks ]Successful outcomes at 1 week,2 weeks,4 weeks, and 8 weeks after voriconazole use
- Non-IFI (invasive fungal infection)-related mortality at 12 weeks [ Time Frame: 12 weeks ]Non-IFI (invasive fungal infection)-related mortality at 12 weeks
- breakthrough IFI [ Time Frame: 12 weeks ]breakthrough IFI
- Adverse drug reactions [ Time Frame: 12 weeks ]Adverse drug reactions (liver function test impairment, visual disturbance, hallucination, photosensitive rash, renal impairment)
Biospecimen Retention: Samples With DNA
- Venous blood sampling will be carried out at steady state for therapeutic drug monitoring(trough sampling:right before the dose)
- Genotyping will be performed using peripheral blood.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01148160
|Korea, Republic of|
|Asan Medical Center, University of Ulsan College of Medicine|
|Seoul, Korea, Republic of, 138-736|