Randomized Clinical Trial to Evaluate the Use of Genotype-based Dosing of Voriconazole
The University of Queensland
Summary
This project aims to address invasive fungal infections in patients, by precision dosing of voriconazole based on CYP2C19 genotype testing with Bayesian dose-forecasting dosing software to develop patient-centric and maximally effective dosing regimens. This study investigates if voriconazole increases the proportion of patients achieving therapeutic exposure at day 8 of dosing compared with standard care; and will assess factors that influence the implementation of genotype testing and dosing software in the healthcare system, including fidelity, feasibility, acceptability and cost-effectiveness. It will recruit at least 104 kids and adults in a parallel-group randomised clinical trial. A hybrid feasibility sub-study will assess the scalability of genotype-directed dosing to ensure sustainable integration of the interventions into the clinical workflow. A health economic sub-study will evaluate the costs, health outcomes and cost-effectiveness of genotype-directed testing compared to standard care.
Description
Participants will be randomly assigned to standard care or precision care. Current standard of care at trial-site institutions uses weight-based (mg/kg) initial dosing of voriconazole, with dose adjustment based on standard therapeutic drug monitoring (TDM) results of measured voriconazole concentrations based on clinical judgement. In precision care, voriconazole dosing will be initiated using current standard dosing. Samples for the TDM and genotype testing will be collected. Based on results of these tests on Day 5 (+/- 1 day) patients will be evaluated for dose adjustment using dosing soft…
Eligibility
- Age range
- 2+ years
- Sex
- All
- Healthy volunteers
- Yes
Inclusion Criteria: * Age ≥ 2 years. * Written informed consent obtained. * Decision to prescribe voriconazole. * Admitted to a trial site, or sufficient outpatient follow-up appointments are feasible Exclusion Criteria: * Post-allogeneic haematopoietic stem cell transplant (HCT) patient, without access to pre HCT DNA * Death is likely imminent within 7 days. * Previously randomised to this trial
Interventions
- Othergenotype-directed dosing with dosing software based on therapeutic drug monitoring
Genotype-directed dosing with dosing software based on therapeutic drug monitoring
Locations (7)
- Fred Hutchinson Cancer CentreSeattle, Washington
- Sydney Children's Hospital NetworkSydney, New South Wales
- Westmead HospitalSydney, New South Wales
- Royal Brisbane & Women's HospitalBrisbane, Queensland
- Children's Hospital QueenslandSouth Brisbane, Queensland
- Royal Adelaide HospitalAdelaide, South Australia