Voriconazole Plasma Level in Intensive Care Unit (ICU) Patients

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Prediction and Adjustment of Voriconazole Plasma Level in Critically Ill Patients

Conditions
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Invasive Fungal Infection

Intervention / Treatment
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* Other: Use of different strategy for voriconazole dosage adjustment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who received voriconazole Exclusion Criteria: Patients allergic to azole(s)

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EA group<br>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<br>* 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.<br>|
| Active Comparator: CA group<br>Voriconazole dosage adjustment according to the levels from day 5, using predefined protocol | Other: Use of different strategy for voriconazole dosage adjustment<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Voriconazole, Therapeutic drug monitoring, Intensive care unit