Prediction and Adjustment of Voriconazole Plasma Level in Critically Ill Patients
Trial Snapshot
- Phase
- Not Applicable
- Status
- Withdrawn
- Sponsor
- Asan Medical Center
- Locations
- 1
- Primary Endpoint
- Appropriateness of voriconazole trough level
Study Overview
Brief Summary
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
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 16 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients who received voriconazole
Exclusion Criteria
- •Patients allergic to azole(s)
Arms & Interventions
EA group
Voriconazole dosage adjustment according to the each measurements of voriconazole levels from day 1, using NONMEM program
Intervention: Use of different strategy for voriconazole dosage adjustment (Other)
CA group
Voriconazole dosage adjustment according to the levels from day 5, using predefined protocol
Intervention: Use of different strategy for voriconazole dosage adjustment (Other)
Outcomes
Primary Outcomes
Appropriateness of voriconazole trough level
Time Frame: Day 3, day 5, day 10, and day 14
Secondary Outcomes
- Mortality(2 week, 4 week, 8 week, 12 week, and 24 week)
- Voriconazole-related adverse event(1 week, 2 week)
Investigators
Sang-Ho Choi
Doctor
Asan Medical Center