Personalized Dosing for Fungal Infections

(PRAGMATIC Trial)

Recruiting in Palo Alto (17 mi)

+6 other locations

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: The University of Queensland

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This project aims to address invasive fungal infections in patients with blood cancer, 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.

Research Team

Eligibility Criteria

This trial is for kids and adults with blood cancer who are dealing with invasive fungal infections. Participants must be able to undergo genotype testing, which will guide the dosing of voriconazole treatment.

Inclusion Criteria

Written informed consent obtained

My doctor has decided to treat me with voriconazole.

I am at least 2 years old.

Exclusion Criteria

I had a stem cell transplant but don't have access to the DNA from before the transplant.

Death is likely imminent within 7 days

Previously randomised to this trial

Treatment Details

Interventions

• Voriconazole (Anti-fungal agent)

Trial Overview The study tests if personalized dosing of voriconazole, guided by genetic testing and special software, can better control fungal infections in blood cancer patients compared to standard care. It's a randomized trial where participants are split into groups by chance.

Participant Groups

Group I: Precision Care Experimental Treatment 1 Intervention

Voriconazole dosing will be initiated using current standard care dosing. Samples for TDM and genotype testing will be collected. Based on the results of these tests on Day 5, 8, 14, and up to day 30 ( ± 1 day) patients will be evaluated for dose adjustment using dosing software that includes patient data including TDM and genotype data.

Group II: Standard Care Active Control 1 Intervention

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 and based on clinical judgement.

Who Is Running the Clinical Trial?

The University of Queensland

Lead Sponsor

Trials

149

Recruited

71,700+

Dr. Paul Griffin

The University of Queensland

Chief Medical Officer

MBBS, BS (Hons) in Microbiology and Immunology

Dr. Dean Moss

The University of Queensland

Chief Executive Officer since 2013

PhD in Medicine from The University of Queensland

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Collaborator

Trials

10

Recruited

2,100+

University of Sydney

Collaborator

Trials

208

Recruited

417,000+

Dr. Othon Gervasio

University of Sydney

Chief Medical Officer since 2023

PhD in Biochemistry from the University of Adelaide

Dr. Alan Taylor

University of Sydney

Chief Executive Officer since 2013

PhD in Medicine from the Garvan Institute of Medical Research, University of Sydney

Royal Adelaide Hospital

Collaborator

Trials

23

Recruited

4,900+

Metro North Hospital and Health Service

Collaborator

Trials

2

Recruited

200+

Sydney Children's Hospitals Network

Collaborator

Trials

37

Recruited

43,300+

Royal Brisbane and Women's Hospital

Collaborator

Trials

33

Recruited

22,900+

Pathology Queensland

Collaborator

Trials

2

Recruited

200+

Western Sydney Local Health District

Collaborator

Trials

42

Recruited

18,600+

University of Melbourne

Collaborator

Trials

193

Recruited

1,287,000+

Dr. Krassimira

University of Melbourne

Chief Medical Officer since 2023

MD certified in Anaesthesiology and Intensive Care

Professor Duncan Maskell

University of Melbourne

Chief Executive Officer since 2018

Master of Arts and Doctor of Philosophy from the University of Cambridge