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

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ClinicalTrials.gov Identifier: NCT01148160
Recruitment Status : Terminated
First Posted : June 22, 2010
Last Update Posted : April 10, 2014
Sponsor:
Information provided by (Responsible Party):
Sung-Han Kim, 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.


Condition or disease Intervention/treatment
Invasive Fungal Infection Drug: voriconazole

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 Type : Observational
Actual Enrollment : 10 participants
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
Study Start Date : August 2010
Actual Primary Completion Date : April 2014
Actual Study Completion Date : April 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Aspergillosis

Group/Cohort Intervention/treatment
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




Primary Outcome Measures :
  1. Successful outcome at 12 weeks after voriconazole use [ Time Frame: 12 weeks ]
    Successful outcome = complete response + partial response Unsuccessful outcome = stable disease + failure of therapy + indeterminate response


Secondary Outcome Measures :
  1. IFI (invasive fungal infection)-related mortality at 12 weeks [ Time Frame: 12 weeks ]
    IFI (invasive fungal infection)-related mortality at 12 weeks

  2. Successful outcomes at various time points [ Time Frame: 1 week, 2 weeks, 4 weeks, and 8 weeks ]
    Successful outcomes at 1 week,2 weeks,4 weeks, and 8 weeks after voriconazole use

  3. Non-IFI (invasive fungal infection)-related mortality at 12 weeks [ Time Frame: 12 weeks ]
    Non-IFI (invasive fungal infection)-related mortality at 12 weeks

  4. breakthrough IFI [ Time Frame: 12 weeks ]
    breakthrough IFI

  5. Adverse drug reactions [ Time Frame: 12 weeks ]
    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.


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Ages Eligible for Study:   15 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01148160


Locations
Korea, Republic of
Asan Medical Center, University of Ulsan College of Medicine
Seoul, Korea, Republic of, 138-736
Sponsors and Collaborators
Asan Medical Center

Additional Information:
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
First Posted: June 22, 2010    Key Record Dates
Last Update Posted: April 10, 2014
Last Verified: April 2014

Keywords provided by Sung-Han Kim, Asan Medical Center:
voriconazole
invasive pulmonary aspergillosis
hematologic malignancy
therapeutic drug monitoring
genetic polymorphism
efficacy
safety

Additional relevant MeSH terms:
Neoplasms
Mycoses
Aspergillosis
Invasive Fungal Infections
Pulmonary Aspergillosis
Invasive Pulmonary Aspergillosis
Hyalohyphomycosis
Dermatomycoses
Lung Diseases, Fungal
Skin Diseases, Infectious
Skin Diseases
Lung Diseases
Respiratory Tract Diseases
Voriconazole
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors