A Trial Comparing Efficacy and Safety of Voriconazole Administered With Therapeutic Drug Monitoring vs. Standard Dosing

Official Title

A Prospective, Randomized Trial Comparing the Efficacy and Safety of Voriconazole Administered With Therapeutic Drug Monitoring vs. Standard Dosing

Summary:

This is a prospective, multicentre, randomized trial to study therapeutic drug monitoring (TDM) of voriconazole among patients with an invasive mould infection (IMI). The primary objective of this study will be to assess the effect of prospective voriconazole TDM on the composite of adverse events (AE) and clinical response.

Trial Description

Primary Outcome:

• Treatment failure

Secondary Outcome:

• The frequency and timing of voriconazole-related AEs
• Clinical response rate
• All cause mortality
• All cause mortality
• The time to death
• Number of dose adjustments
• The number of switch to and addition of other antifungals

This is a prospective study of patients who receive voriconazole as treatment for an IMI (proven, probable, and possible by the EORTC/MSG definitions), other than zygomycosis. Patients will be randomized to receive either standard dosing or dosing based on TDM, stratified by whether initial voriconazole therapy is PO or IV. Assessment of outcomes will be made 42 days after start of voriconazole. An additional follow up for safety reporting will be performed 4weeks after completion of voriconazole The patients will be randomized to:

• Prospective TDM: voriconazole dose will be adjusted based on per protocol obtained TDM levels, and

• Standard dosing: standard doses of voriconazole will be used. In the prospective TDM arm, voriconazole TDM will be performed in real time at each site and results will be reported to treating physicians for dose adjustment. All efforts will be taken to obtain results within 24 hours of blood sample collection. In the standard dosing arm, blood samples will be collected, stored, and batched for voriconazole levels to be tested retrospectively. Voriconazole plasma levels will be measured by validated high performance liquid chromatography (HPLC) assays as detailed. Voriconazole trough levels will be performed on Day Baseline/Screening, 5, 14, 28, and 42. Voriconazole peak level will be measured on Day 5. Trough voriconazole levels will be obtained in case of an event, defined as suspected drug-associated toxicity and/or clinical failure. Assessment of AEs for all patients will be monitored during the study and response to treatment will be assessed. The composite of overall AE/clinical failure will be assessed on day 42.

View this trial on ClinicalTrials.gov