Clinical trial NCT01148160: Voriconazole Trough Plasma Levels : Genetic Polymorphism, Efficacy, Safety in Patients With Hematologic Malignancy
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 type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Invasive Fungal Infection
Keywords: voriconazole
invasive pulmonary aspergillosis
hematologic malignancy
therapeutic drug monitoring
genetic polymorphism
efficacy
safety
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
First posted: 2010-06-22
Enrollment: 10
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Successful outcome at 12 weeks after voriconazole use
timeFrame: 12 weeks
Secondary outcomes:
measure: IFI (invasive fungal infection)-related mortality at 12 weeks
timeFrame: 12 weeks
measure: Successful outcomes at various time points
timeFrame: 1 week, 2 weeks, 4 weeks, and 8 weeks
measure: Non-IFI (invasive fungal infection)-related mortality at 12 weeks
timeFrame: 12 weeks
measure: breakthrough IFI
timeFrame: 12 weeks
measure: Adverse drug reactions
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center, University of Ulsan College of Medicine
Study officials:
References: