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

Voriconazole Trough Plasma Levels : Genetic Polymorphism, Efficacy, Safety in Patients With Hematologic Malignancy
This study is currently recruiting participants.
Verified February 2012 by Asan Medical Center

First Received on June 18, 2010.  
Last Updated on February 8, 2012  
History of Changes
Sponsor: Asan Medical Center
Information provided by (Responsible Party): Sung-Han Kim, Asan Medical Center
ClinicalTrials.gov Identifier: NCT01148160
  Purpose

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 Intervention
Invasive Fungal Infection Drug: voriconazole

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: The Correlation of Voriconazole Trough Plasma Levels With Genetic Polymorphism, Efficacy, and Safety Outcomes in Hematologic Malignancy Patients With Invasive Pulmonary Aspergillosis

Resource links provided by NLM:

Further study details as provided by Asan Medical Center:

Primary Outcome Measures:

  • Successful outcome at 12 weeks after voriconazole use [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Successful outcome = complete response + partial response Unsuccessful outcome = stable disease + failure of therapy + indeterminate response

Secondary Outcome Measures:

  • IFI (invasive fungal infection)-related mortality at 12 weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Non-IFI (invasive fungal infection)-related mortality at 12 weeks

  • breakthrough IFI [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    breakthrough IFI

  • Adverse drug reactions [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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.

Estimated Enrollment: 60
Study Start Date: August 2010
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)

Groups/Cohorts

Assigned Interventions
1

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

intravenous, oral administration

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

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

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
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01148160

Contacts
Contact: Sung-Han Kim, M.D. +82-2-3010-3114 ext 3305 shkimmd@amc.seoul.kr
Contact: Yeon-Joo Lee +82-2-3010-3114 ext 5224 yeonjoo@amc.seoul.kr

Locations
Korea, Republic of
Asan Medical Center, University of Ulsan College of Medicine Recruiting
Seoul, Korea, Republic of, 138-736
Contact: Sung-Han Kim, M.D.     +82-2-3010-3114 ext 3305     shkimmd@amc.seoul.kr    
Contact: Yeon-Joo Lee     +82-2-3010-3114 ext 5224     yeonjoo@amc.seoul.kr    
Principal Investigator: Sung-Han Kim, M.D.            
Sponsors and Collaborators
Asan Medical Center
  More Information

No publications provided

Responsible Party: Sung-Han Kim, Assistantant Professor, Asan Medical Center
ClinicalTrials.gov Identifier: NCT01148160    
History of Changes
Other Study ID Numbers: VCZ-IPA-HEM-2010
Study First Received: June 18, 2010
Last Updated: February 8, 2012
Health Authority: South Korea: Institutional Review Board

Keywords provided by Asan Medical Center:

voriconazole
invasive pulmonary aspergillosis
hematologic malignancy
therapeutic drug monitoring
genetic polymorphism
efficacy
safety

Additional relevant MeSH terms:

Aspergillosis
Neoplasms
Mycoses
Invasive Pulmonary Aspergillosis
Hematologic Neoplasms
Pulmonary Aspergillosis
Lung Diseases, Fungal
Lung Diseases
Respiratory Tract Diseases
Neoplasms by Site
Hematologic Diseases
Voriconazole
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 21, 2012

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