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

Invasive Fungal Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01148160
• Other study ID #: VCZ-IPA-HEM-2010
• Status: Terminated
• Phase: N/A
• First received: June 18, 2010
• Last updated: April 9, 2014
• Start date: August 2010
• Est. completion date: April 2014

Study information

• Verified date: April 2014
• Source: Asan Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Korea: Institutional Review Board
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years and older

Eligibility

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

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Invasive Fungal Infection
• Invasive Pulmonary Aspergillosis
• Mycoses
• Pulmonary Aspergillosis

Intervention

Drug:
• voriconazole
intravenous, oral administration

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center, University of Ulsan College of Medicine	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Asan Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	IFI (invasive fungal infection)-related mortality at 12 weeks	IFI (invasive fungal infection)-related mortality at 12 weeks	12 weeks	No
Secondary	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	No
Secondary	Non-IFI (invasive fungal infection)-related mortality at 12 weeks	Non-IFI (invasive fungal infection)-related mortality at 12 weeks	12 weeks	No
Secondary	breakthrough IFI	breakthrough IFI	12 weeks	No
Secondary	Adverse drug reactions	Adverse drug reactions (liver function test impairment, visual disturbance, hallucination, photosensitive rash, renal impairment)	12 weeks	No

External Links

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