Therapeutic Drug Monitoring (TDM) of Voriconazole and Correlation With CYP2C19 Genotype in Korean Populations

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2008 by The Catholic University of Korea.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
The Catholic University of Korea
ClinicalTrials.gov Identifier:
NCT00673348
First received: May 5, 2008
Last updated: July 22, 2008
Last verified: June 2008
  Purpose

Voriconazole (VCZ), the antifungal drug active against Candida and Aspergillus is a substrate of CYP2C19, whose proportion of poor metabolizers is about ~20% in Asian population. The AUC's of VCZ differs over 4 folds by CYP2C19 genotypes of homozygotic wild type, heterozygote, and homozygotic poor metabolizers. The Asian population enrolled in the metabolism of VCZ were mainly Japanese and Chinese, without Korean subjects. The proportion of poor metabolizers in Korean population is known to be around 12% (Pharmacogenetics. 1996 Dec;6(6):547-51). The importance of CYP2C19 genotypes on the pharmacokinetics (PK) of voriconazole is well established, Hence, it is desirable to individualize the dosage regimen of VCZ according to the genotypes of patients. Fungal infection in immunocompromised patients is a life threatening condition which needs critical care. Although the PK change by genotypes are well known, its clinical implication or need for different dosage regimen by genotypes is not established, yet.


Condition
Mycoses
Neutropenia
Bone Marrow Transplantation

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: A Prospective Observational Study of Plasma Voriconazole Concentration Measurement and Its Correlation With CYP2C19 Genotype in Korean Patients

Resource links provided by NLM:


Further study details as provided by The Catholic University of Korea:

Primary Outcome Measures:
  • To regular setting of voriconazole TDM & establish relationship with efficacy and safety [ Time Frame: Prospective ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To apply population pharmacokinetic-pharmacodynamic modeling and simulation technique on the clinical research of antifungal drugs. [ Time Frame: Prospective ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA
  • Two times of venous blood sampling will be carried out at steady state. Three ml of venous blood is sampled right before the morning dose (trough sampling). The second sampling is carried out at any time point within 2-4 hours after the morning dose (peak sampling). To obtain the exact dose and sampling history, at least three dosing times around the trough and peak sampling will be recorded to the minute. Sampling time will also be recorded as clock time.
  • Genotyping of CYP2C19 will also be performed using 3 ml of peripheral blood sampled into EDTA tubes.

Estimated Enrollment: 40
Study Start Date: May 2008
Estimated Study Completion Date: April 2010
Estimated Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Groups/Cohorts
1
Patients suspected of invasive fungal infection (proven or probable cases) with immunocompromised state (for example, during neutropenia, receiving HSCT) in Catholic Hematopoietic Stem Cell Transplantation [HSCT] Center in Seoul, Korea.

Detailed Description:

The investigators are trying to set up voriconazole (VCZ) therapeutic drug monitoring (TDM) & establish relationship with efficacy and safety in Korea. The investigators also want to propose the optimal dosage regimen for VCZ over different genotypes of CYP2C19 in the immunocompromised patients in Korea.

  Eligibility

Ages Eligible for Study:   15 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients suspected of invasive fungal infection (proven or probable cases) with immunocompromised state (for example, during neutropenia, receiving HSCT) in Catholic Hematopoietic Stem Cell Transplantation [HSCT] Center in Seoul, Korea.

Criteria

Inclusion Criteria:

  • Immunocompromised adults who are treated with voriconazole due to proven or probable invasive fungal infections

Exclusion Criteria:

  • Patients who have been treated with other investigational drugs
  • Patients with liver dysfunction (aminotransferase level ≥ 5 times the upper limit of normal, bilirubin or alkaline phosphatase level > 3 times the upper limit of normal)
  • Patients with renal dysfunction (Cr level > 2.5 times the upper limit of normal)
  • Pregnant women
  • Patients younger than 15 years of age
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00673348

Contacts
Contact: Dong-Gun Lee, M.D., Ph.D. 82-2-3779-1114 ext 1099 symonlee@catholic.ac.kr
Contact: Dong-Seok Yim, M.D., Ph.D. 82-2-590-1114 ext 1201 yimds@catholic.ac.kr

Locations
Korea, Republic of
St. Mary's Hospital Not yet recruiting
Seoul, Korea, Republic of, 150-713
Contact: Dong-Gun Lee, M.D., Ph.D.    82-2-3779-1114 ext 1099    symonlee@catholic.ac.kr   
Principal Investigator: Dong-Gun Lee, M.D., Ph.D.         
St. Mary's Hospital Recruiting
Seoul, Korea, Republic of, 150-713
Contact: Hae-Young Youn, Pharm D    82-2-3779-1114 ext 1216    baram@catholic.ac.kr   
Sponsors and Collaborators
The Catholic University of Korea
Investigators
Principal Investigator: Dong-Gun Lee, M.D., Ph.D. St. Mary's Hospital, The Catholic Univ. of Korea
  More Information

No publications provided by The Catholic University of Korea

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dong-Gun Lee / Assistant Professor, Division of Infectious Diseases, Department of Internal Medicine
ClinicalTrials.gov Identifier: NCT00673348     History of Changes
Other Study ID Numbers: VCZ_TDM_Korea
Study First Received: May 5, 2008
Last Updated: July 22, 2008
Health Authority: South Korea: Institutional Review Board

Keywords provided by The Catholic University of Korea:
Mycoses
Voriconazole

Additional relevant MeSH terms:
Mycoses
Neutropenia
Agranulocytosis
Leukopenia
Leukocyte Disorders
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 September 30, 2014