Voriconazole Trough Plasma Levels : Genetic Polymorphism, Efficacy, Safety in Patients With Hematologic Malignancy

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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The Correlation of Voriconazole Trough Plasma Levels With Genetic Polymorphism, Efficacy, and Safety Outcomes in Hematologic Malignancy Patients With Invasive Pulmonary Aspergillosis

Conditions
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Invasive Fungal Infection

Intervention / Treatment
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* Drug: voriconazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: all items below male or female ≥ 15 years of age immunocompromised patients with hematologic disorders patients received voriconazole due to treat proven, probable invasive (pulmonary) aspergillosis Exclusion Criteria: severe hepatic dysfunction (t.bil, AST, ALT, ALP > 5 x upper normal limit) who experienced hypersensitivity to azoles pregnant women

Ages Eligible for Study
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Minimum Age: 15 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1<br>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 | Drug: voriconazole<br>* intravenous, oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Successful outcome at 12 weeks after voriconazole use | Successful outcome = complete response + partial response Unsuccessful outcome = stable disease + failure of therapy + indeterminate response | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IFI (invasive fungal infection)-related mortality at 12 weeks | IFI (invasive fungal infection)-related mortality at 12 weeks | 12 weeks | 
| Successful outcomes at various time points | Successful outcomes at 1 week,2 weeks,4 weeks, and 8 weeks after voriconazole use | 1 week, 2 weeks, 4 weeks, and 8 weeks | 
| Non-IFI (invasive fungal infection)-related mortality at 12 weeks | Non-IFI (invasive fungal infection)-related mortality at 12 weeks | 12 weeks | 
| breakthrough IFI | breakthrough IFI | 12 weeks | 
| Adverse drug reactions | Adverse drug reactions (liver function test impairment, visual disturbance, hallucination, photosensitive rash, renal impairment) | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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voriconazole, invasive pulmonary aspergillosis, hematologic malignancy, therapeutic drug monitoring, genetic polymorphism, efficacy, safety