Voriconazole Prophylaxis Against Aspergillosis in Lung Transplant Recipients

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00177827
First received: September 13, 2005
Last updated: December 2, 2009
Last verified: December 2009
  Purpose

A fixed dosage regimen of voriconazole is routinely used for prophylaxis of aspergillosis in lung transplant patients at our institution. We hypothesize that use of a fixed dosage voriconazole regimen leads to large degree of variability in drug exposure among lung transplant patients and consequently, therapeutic failures or toxicity. This is a three part study which will examine plasma and lung voriconazole concentrations achieved with the prophylactic regimen and assess for a correlation between these concentrations with efficacy and toxicity. We aim to conduct an initial pilot study in 12 lung transplant patients to characterize the pharmacokinetic profile of voriconazole with both intravenous and oral doses. The data gathered from the pilot pharmacokinetic study will then be utilized to correlate trough concentrations with total voriconazole drug exposure as measured by area under the plasma concentration versus time curve (AUC). Additionally, trough concentrations will be followed over nine weeks of the prophylactic treatment period in a larger cohort of patients to determine maintenance of consistency in trough concentrations and whether the plasma concentrations are predictive of efficacy and toxicity. Voriconazole lung concentrations will be measured in a pilot study of 12 patients who undergo a bronchoscopy procedure as part of their standard medical care in order to determine the relationship between plasma and lung concentrations. The information obtained from this three phase study will be utilized to characterize the pharmacokinetics of voriconazole in lung transplant patients. Further, it will be used to define an optimal therapeutic voriconazole regimen that will be individualized to target specific concentrations in the lung and plasma to maximize efficacy and minimize toxicity


Condition Phase
Post Lung Transplantation
Phase 4

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Voriconazole Prophylaxis Against Aspergillosis in Lung Transplant Recipients: Pharmacokinetics and Correlation Between Plasma and Lung Concentrations With Toxicity/Efficacy

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Estimated Enrollment: 104
Study Start Date: March 2004
Study Completion Date: March 2006
Detailed Description:

Blood samples (5 mL) will be collected either from an existing indwelling intravenous catheter or via a catheter placed by a research nurse or phlebotomist. The samples will be centrifuged at 1,500 g for 10 minutes within 60 minutes of collection. The plasma will be separated into two separate cryovials and stored at - 80 C until the time of assay for Voriconazole.A standardized data collection sheet will be created by the study investigators and utilized to gather pertinent information on each study participant from the patient medical records and electronic databases. The type of information collected will include, but will not be limited to, demographic information, transplant history, periodic serum chemistry and hematology monitoring, medication regimen, plasma voriconazole level monitoring and efficacy and safety monitoring parameters.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Chart review

Criteria

Inclusion Criteria:

  • Male or female lung transplant recipients, greater than 18 years old, who are initiated on the voriconazole prophylactic regimen (Figure 1) by their transplant physician as standard care will be eligible for inclusion in the study.

Exclusion Criteria:

  • Patients receiving voriconazole to treat an active fungal infection will be excluded. Patients that are concurrently receiving medications that are documented to affect voriconazole pharmacokinetics will be excluded. The agents included, but may not be limited to the following ;carbamazepine, phenytoin, omeprazole, rifabutin and rifampin.10
  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: NCT00177827

Locations
United States, Pennsylvania
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: Blair Capitano, Pharm D University of Pittsburgh
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00177827     History of Changes
Other Study ID Numbers: IRB# 0304017
Study First Received: September 13, 2005
Last Updated: December 2, 2009
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Aspergillosis
Dermatomycoses
Hyalohyphomycosis
Infection
Mycoses
Skin Diseases
Skin Diseases, Infectious
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 21, 2014