About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Age ≥ 2 years.
Written informed consent obtained.
Decision to prescribe voriconazole.
Admitted to a trial site, or sufficient outpatient follow-up appointments are feasible
Disqualifiers
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
Trial design
Parallel
Treatments tested in this trial
genotype-directed dosing with dosing software based on therapeutic drug monitoring
Other interventionGenotype-directed dosing with dosing software based on therapeutic drug monitoring
Treatment groups
Trial outcomes
Primary outcomes
Therapeutic trough voriconazole concentration at Day 8
Proportion of patients with measured therapeutic trough voriconazole concentration at Day 9 (+/- 1 day)
Secondary outcomes
Simulated therapeutic trough voriconazole exposure at Day 8
Proportion of patients with simulated therapeutic trough voriconazole exposure at Day 8
Measured therapeutic trough voriconazole exposure at Day 14.
Proportion of patients with measured therapeutic trough voriconazole exposure at Day 14.
Simulated therapeutic trough voriconazole exposure at Day 14
Proportion of patients with simulated therapeutic trough voriconazole exposure at Day 14
Measured therapeutic trough voriconazole exposure at both Days 8 and 14
Proportion of patients with measured therapeutic trough voriconazole exposure at both Days 8 and 14
Sponsors and contacts
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The University of Queensland
Lead sponsor
Metro North Hospital and Health Service
Collaborator
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Collaborator
University of Sydney
Collaborator
Western Sydney Local Health District
Collaborator
Sydney Children's Hospitals Network
Collaborator
Peter MacCallum Cancer Centre, Australia
Collaborator
University of Melbourne
Collaborator
Royal Adelaide Hospital
Collaborator
Pathology Queensland
Collaborator
Royal Brisbane and Women's Hospital
Collaborator
Lady Cilento Children's Hospital, Brisbane
Collaborator