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

NCT01148160 | Terminated

• 1 other identifier: VCZ-IPA-HEM-2010
• Study Type: observational
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Invasive Fungal Infection

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (5)

• IFI (invasive fungal infection)-related mortality at 12 weeks

  12 weeks

• Successful outcomes at various time points

  1 week, 2 weeks, 4 weeks, and 8 weeks

• Non-IFI (invasive fungal infection)-related mortality at 12 weeks

  12 weeks

• breakthrough IFI

  12 weeks

• Adverse drug reactions

  12 weeks

Study Arms (1)

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

Interventions

voriconazole DRUG

intravenous, oral administration

1

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• male or female ≥ 15 years of age
• immunocompromised patients with hematologic disorders
• patients received voriconazole due to treat proven, probable invasive (pulmonary) aspergillosis

You may not qualify if:

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

Sponsors & Collaborators

• Asan Medical Center: lead

Study Sites (1)

Asan Medical Center, University of Ulsan College of Medicine

Seoul, 138-736, South Korea

Location

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.

MeSH Terms

Conditions

Invasive Fungal Infections; Invasive Pulmonary Aspergillosis; Hematologic Neoplasms

Interventions

Voriconazole

Condition Hierarchy (Ancestors)

Mycoses; Bacterial Infections and Mycoses; Infections; Pulmonary Aspergillosis; Aspergillosis; Lung Diseases, Fungal; Lung Diseases; Respiratory Tract Diseases; Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistantant Professor

Study Record Dates

• First Submitted: June 18, 2010
• First Posted: June 22, 2010
• Study Start: August 1, 2010
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: April 10, 2014

Record last verified: 2014-04

Locations

KR (1)