Voriconazole Plasma Level in Intensive Care Unit (ICU) Patients

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by (Responsible Party):
Sang-Ho Choi, Asan Medical Center
ClinicalTrials.gov Identifier:
NCT01185405
First received: August 17, 2010
Last updated: September 29, 2013
Last verified: September 2013
  Purpose

Voriconazole, a newer triazole-derivative, has become the drug of choice for many invasive fungal infections, including invasive Aspergillosis. Recently, therapeutic drug monitoring of voriconazole has been issued because of wide variations and unpredictability of voriconazole blood concentration. The objective of this study is 1) to characterize the pharmacokinetics of voriconazole in ICU patients on voriconazole prophylaxis or treatment, and 2) to develop and evaluate the prediction and adjustment models for voriconazole plasma levels.


Condition Intervention
Invasive Fungal Infection
Other: Use of different strategy for voriconazole dosage adjustment

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Prediction and Adjustment of Voriconazole Plasma Level in Critically Ill Patients

Resource links provided by NLM:


Further study details as provided by Asan Medical Center:

Primary Outcome Measures:
  • Appropriateness of voriconazole trough level [ Time Frame: Day 3, day 5, day 10, and day 14 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Mortality [ Time Frame: 2 week, 4 week, 8 week, 12 week, and 24 week ] [ Designated as safety issue: No ]
  • Voriconazole-related adverse event [ Time Frame: 1 week, 2 week ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: August 2010
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EA group
Voriconazole dosage adjustment according to the each measurements of voriconazole levels from day 1, using NONMEM program
Other: Use of different strategy for voriconazole dosage adjustment
Patients will be randomly assigned into 2 groups: conventional adjustment group (CA group) and early adjustment group (EA group). Voriconazole plasma levels will be measured on day 1 (both peak and trough levels), day 3, day 5, day 10, and day 14 (all trough levels). For CA group patients, voriconazole dosage will be adjusted according to the trough levels of day 5 (steady-state level). Predefined dose adjustment protocol will be used (< 1 µg/ml: 50% increase, 1~5.5 µg/ml: no change, > 5.5 µg/ml: 50% decrease). For EA group patients, voriconazole dosage will be adjusted according to the each measurements of voriconazole levels from day 1. Adjusted dosage will be calculated using the NONMEN software.
Active Comparator: CA group
Voriconazole dosage adjustment according to the levels from day 5, using predefined protocol
Other: Use of different strategy for voriconazole dosage adjustment
Patients will be randomly assigned into 2 groups: conventional adjustment group (CA group) and early adjustment group (EA group). Voriconazole plasma levels will be measured on day 1 (both peak and trough levels), day 3, day 5, day 10, and day 14 (all trough levels). For CA group patients, voriconazole dosage will be adjusted according to the trough levels of day 5 (steady-state level). Predefined dose adjustment protocol will be used (< 1 µg/ml: 50% increase, 1~5.5 µg/ml: no change, > 5.5 µg/ml: 50% decrease). For EA group patients, voriconazole dosage will be adjusted according to the each measurements of voriconazole levels from day 1. Adjusted dosage will be calculated using the NONMEN software.

Detailed Description:

Patients will be randomly assigned into 2 groups: conventional adjustment group (CA group) and early adjustment group (EA group). Voriconazole plasma levels will be measured on day 1 (both peak and trough levels), day 3, day 5, day 10, and day 14 (all trough levels). For CA group patients, voriconazole dosage will be adjusted according to the trough levels of day 5 (steady-state level). Predefined dose adjustment protocol will be used (< 1 µg/ml: 50% increase, 1~5.5 µg/ml: no change, > 5.5 µg/ml: 50% decrease). For EA group patients, voriconazole dosage will be adjusted according to the each measurements of voriconazole levels from day 1. Adjusted dosage will be calculated using the NONMEN software. The target range of trough level is between 1.0 µg/ml and 5.5 µg/ml. The appropriateness of voriconazole level (day 5, day 10, and day 14), mortality, ICU stay, and the frequency of voriconazole-related adverse events will be compared. CYP2C19 polymorphism will be analyzed for all patients.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients who received voriconazole

Exclusion Criteria:

  • Patients allergic to azole(s)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01185405

Locations
Korea, Republic of
Asan Medical Center
Seoul, Korea, Republic of, 138-736
Sponsors and Collaborators
Asan Medical Center
Investigators
Principal Investigator: Sang-Ho Choi, MD Asan Medical Center
  More Information

No publications provided

Responsible Party: Sang-Ho Choi, Doctor, Asan Medical Center
ClinicalTrials.gov Identifier: NCT01185405     History of Changes
Other Study ID Numbers: AVORI
Study First Received: August 17, 2010
Last Updated: September 29, 2013
Health Authority: Korea: Food and Drug Administration

Keywords provided by Asan Medical Center:
Voriconazole
Therapeutic drug monitoring
Intensive care unit

Additional relevant MeSH terms:
Mycoses
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 April 17, 2014