Voriconazole Plasma Level in Intensive Care Unit (ICU) Patients

Prediction and Adjustment of Voriconazole Plasma Level in Critically Ill Patients

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.

Study Overview

• Status: Withdrawn
• Conditions: Invasive Fungal Infection
• Intervention / Treatment: Other: Use of different strategy for voriconazole dosage adjustment

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.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients who received voriconazole

Exclusion Criteria:

• Patients allergic to azole(s)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Appropriateness of voriconazole trough level	Day 3, day 5, day 10, and day 14

Secondary Outcome Measures

Outcome Measure	Time Frame
Mortality	2 week, 4 week, 8 week, 12 week, and 24 week
Voriconazole-related adverse event	1 week, 2 week

Collaborators and Investigators

• Sponsor: Asan Medical Center
• Investigators: Principal Investigator: Sang-Ho Choi, MD, Asan Medical Center

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Anticipated): December 1, 2013
• Study Completion (Anticipated): December 1, 2013

Study Registration Dates

• First Submitted: August 17, 2010
• First Submitted That Met QC Criteria: August 19, 2010
• First Posted (Estimate): August 20, 2010

Study Record Updates

• Last Update Posted (Estimate): October 1, 2013
• Last Update Submitted That Met QC Criteria: September 29, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: Voriconazole; Therapeutic drug monitoring; Intensive care unit
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Invasive Fungal Infections; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Voriconazole
• Other Study ID Numbers: AVORI