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

Terminated

• Conditions: Invasive Fungal Infection
• Interventions: Drug: voriconazole

• Registration Number: NCT01148160
• Lead Sponsor: Asan Medical Center

Brief Summary

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

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 Timeline

• Study First Submitted: 2010-06-18
• Study First Submitted QC: 2010-06-21
• Study First Posted: 2010-06-22
• Study Start: 2010-08
• Status Verified: 2014-04
• Primary Completion: 2014-04
• Study Completion: 2014-04
• Last Update Submitted: 2014-04-09
• Last Update Posted: 2014-04-10

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 10

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

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Exclusion Criteria

• severe hepatic dysfunction (t.bil, AST, ALT, ALP > 5 x upper normal limit)
• who experienced hypersensitivity to azoles
• pregnant women

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
1	voriconazole	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

Primary Outcome Measures

Name	Time	Method
Successful outcome at 12 weeks after voriconazole use	12 weeks	Successful outcome = complete response + partial response Unsuccessful outcome = stable disease + failure of therapy + indeterminate response

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Asan Medical Center, University of Ulsan College of Medicine; 🇰🇷 Seoul, Korea, Republic of