Voriconazole Blood Levels and Toxicity

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00359541
First received: August 1, 2006
Last updated: June 26, 2010
Last verified: June 2010
  Purpose

This study will look at how voriconazole, a drug used to treat or protect against fungal infections, affects the body. Adverse effects associated with voriconazole include skin problems and temporary changes in vision, mental status and liver function. There is some evidence that these side effects may be more intense when there are high levels of the drug in the blood. The amount of voriconazole in the body is determined by how much of the drug the patient receives and by the patient's ability to inactivate and excrete it, which may be determined in part by genes. This study will examine: 1) side effects patients develop from voriconazole; 2) whether the side effects experienced are related to the concentration of drug in the body; and 3) the role of genes in determining how quickly the body inactivates and excretes the drug.

Patients 12 and older who are participating in studies in the National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute (NCI) or the National Heart, Lung, and Blood Institute (NHLBI) and have been treated with voriconazole for 15 days or less may be eligible for this study.

Participation involves the following:

  • Identification and recording of adverse effects patients experience due to voriconazole treatment
  • Collection of basic information about the patient's medical history and treatment
  • Blood draws once a week during the patient's hospitalization
  • Collection of routine laboratory test results ordered by the patient's doctor
  • Blood draw to identify genes responsible for voriconazole inactivation
  • Weekly monitoring for the possibility of voriconazole adverse effects
  • Blood draw to measure blood levels of voriconazole when the drug is stopped, if it is stopped because of an adverse effect
  • Evaluations at outpatient visits, including a blood draw to measure voriconazole blood levels

Participation in the study ends 7 days after voriconazole treatment is stopped because it is no longer needed.


Condition
Pharmacology

Study Type: Observational
Official Title: Voriconazole Plasma Concentration and Toxicity

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Enrollment: 98
Study Start Date: January 2006
Estimated Study Completion Date: June 2010
Detailed Description:

Voriconazole (Vfend(Registered Trademark), Pfizer) has achieved common usage at the NIH (National Institutes of Health) Clinical Research Center for the treatment of fungal infections in immunosuppressed patients. Toxicity includes relatively frequent but reversible changes in vision and more infrequent, potentially serious hepatotoxicity, decreased cognitive function and rash. Incidence of these more serious adverse events has been difficult to ascertain because of the morbidity of underlying disease in patients receiving voriconazole, but a minimum estimate is 10 percent. It is known that voriconazole plasma concentrations vary between patients over a fifty-fold range but it is not known whether toxicity is related to plasma drug exposure. The reason for the differing voriconazole plasma concentrations between normal individuals is partly due to genetic variations in hepatic cytochrome enzymes CYP2C9 and CYP2C19 (Cytochrome P450, family 2, subfamily C, polypeptide 9 and 19, respectively). In patients with underlying illness, drug interactions and decreased hepatic drug clearance may contribute to variability.

The purpose of the study is to record prospectively the adverse effects of voriconazole in Clinical Center patients who have been prescribed the drug by their primary physician. We will ask the primary physician to order a trough voriconazole plasma levels once a week. The test will not be reported to the physician. Because interpretation of the test is unknown, the physicians will be blinded to the report. Rather, the primary objective of the study is to analyze the voriconazole plasma concentrations when the study is completed to determine if there is a concentration and duration of drug exposure that correlates with toxicity. A secondary objective is to determine the 2C9 and 2C19 genotype of patients and search for possible correlations between genotype and plasma voriconazole concentrations. Administration of other drugs given to the patient will be tracked to analyze whether any previously unknown drug interactions seem to have changed the voriconazole plasma concentration. The study will also determine the incidence of adverse effects of voriconazole in our patient population.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Patients, at least 12 years old with no restriction of gender, race or disabilities, followed by the National Institute of Allergy and Infectious Diseases (NIAID), National Cancer Institute (NCI) and National Heart Lung and Blood Institute (NHLBI) who begin treatment with voriconazole either oral or intravenous.

Patients who have a previous voriconazole course at least 7 days before current course.

EXCLUSION CRITERIA:

Time elapsed greater than 15 days from initiation of voriconazole treatment for inpatients and greater than 30 days from initiation of voriconazole treatment for outpatients.

Patients who the medical staffs caring for the patient not want entered into the study.

Patients unable to give informed consent, due to the severity of their medical condition (Comatose patients, ICU patients under sedation).

  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: NCT00359541

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00359541     History of Changes
Other Study ID Numbers: 060077, 06-I-0077
Study First Received: August 1, 2006
Last Updated: June 26, 2010
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
CYP2C9
CYP2C19
Pharmacology
Genotype
Metabolism

Additional relevant MeSH terms:
Voriconazole
14-alpha Demethylase Inhibitors
Anti-Infective Agents
Antifungal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014