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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06510699




Registration number
NCT06510699
Ethics application status
Date submitted
14/07/2024
Date registered
19/07/2024
Date last updated
19/07/2024

Titles & IDs
Public title
Pharmacogenomics for Better Treatment of Fungal Infections in Cancer
Scientific title
Randomized Clinical Trial to Evaluate the Use of Genotype-based Dosing of Voriconazole in Patients With Haematological Malignancy
Secondary ID [1] 0 0
PRAGMATIC 01
Universal Trial Number (UTN)
Trial acronym
PRAGMATIC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fungal Infection 0 0
Haematological Malignancy 0 0
Blood Cancer 0 0
Infectious Disease 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Sexually transmitted infections
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - genotype-directed dosing with dosing software based on therapeutic drug monitoring

Experimental: Precision Care - 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.

No intervention: Standard 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 and based on clinical judgement.


Other interventions: genotype-directed dosing with dosing software based on therapeutic drug monitoring
Genotype-directed dosing with dosing software based on therapeutic drug monitoring
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Therapeutic trough voriconazole concentration at Day 8
Timepoint [1] 0 0
Day 8
Secondary outcome [1] 0 0
Simulated therapeutic trough voriconazole exposure at Day 8
Timepoint [1] 0 0
Day 8
Secondary outcome [2] 0 0
Measured therapeutic trough voriconazole exposure at Day 14.
Timepoint [2] 0 0
Day 14
Secondary outcome [3] 0 0
Simulated therapeutic trough voriconazole exposure at Day 14
Timepoint [3] 0 0
Day 14
Secondary outcome [4] 0 0
Measured therapeutic trough voriconazole exposure at both Days 8 and 14
Timepoint [4] 0 0
Days 8 and 14
Secondary outcome [5] 0 0
Simulated therapeutic trough voriconazole exposure at both Days 8 and 14
Timepoint [5] 0 0
Days 8 and 14
Secondary outcome [6] 0 0
Simulated therapeutic trough voriconazole exposure from Day 8 to Day 30
Timepoint [6] 0 0
Day 8 to Day 30
Secondary outcome [7] 0 0
Days to achieve first measured therapeutic trough voriconazole exposure
Timepoint [7] 0 0
Assessed over 30 days
Secondary outcome [8] 0 0
Doses to achieve first measured therapeutic trough voriconazole exposure.
Timepoint [8] 0 0
Assessed over 30 days
Secondary outcome [9] 0 0
Percent difference in dose when dose adjustment is performed
Timepoint [9] 0 0
Assessed over 30 days
Secondary outcome [10] 0 0
Number of days of antifungal therapy
Timepoint [10] 0 0
Assessed over 30 days
Secondary outcome [11] 0 0
Number of doses of antifungal therapy
Timepoint [11] 0 0
Assessed over 30 days
Secondary outcome [12] 0 0
Clinical cure or stable disease
Timepoint [12] 0 0
Assessed over 30 days
Secondary outcome [13] 0 0
Patients with no reported fungal infection during course
Timepoint [13] 0 0
Assessed over 30 days
Secondary outcome [14] 0 0
Hospital free days
Timepoint [14] 0 0
Day 30
Secondary outcome [15] 0 0
Length of hospital stay post-randomisation
Timepoint [15] 0 0
Assessed over 30 days
Secondary outcome [16] 0 0
Number of patients experiencing at least one adverse event
Timepoint [16] 0 0
Assessed over 30 days
Secondary outcome [17] 0 0
Number and type of adverse events
Timepoint [17] 0 0
Assessed over 30 days
Secondary outcome [18] 0 0
All-cause mortality at 30 days
Timepoint [18] 0 0
Assessed over 30 days
Secondary outcome [19] 0 0
Clinical success
Timepoint [19] 0 0
Assessed over 30 days

Eligibility
Key inclusion criteria
* Age = 2 years.
* Written informed consent obtained.
* Decision to prescribe voriconazole.
* Diagnosed with haematological malignancy or disorder.
* Admitted to a trial site, or sufficient outpatient follow-up appointments are feasible
Minimum age
2 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
1/11/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
2/09/2026
Actual
Sample size
Target
104
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Sydney Children's Hospital Network - Sydney
Recruitment hospital [2] 0 0
Westmead Hospital - Sydney
Recruitment hospital [3] 0 0
Royal Brisbane & Women's Hospital - Brisbane
Recruitment hospital [4] 0 0
Children's Hospital Queensland - South Brisbane
Recruitment hospital [5] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [6] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
21452031 - Sydney
Recruitment postcode(s) [2] 0 0
2145 - Sydney
Recruitment postcode(s) [3] 0 0
4029 - Brisbane
Recruitment postcode(s) [4] 0 0
4029 - South Brisbane
Recruitment postcode(s) [5] 0 0
5000 - Adelaide
Recruitment postcode(s) [6] 0 0
3053 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Washington

Funding & Sponsors
Primary sponsor type
Other
Name
The University of Queensland
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Metro North Hospital and Health Service
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
University of Sydney
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Western Sydney Local Health District
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Sydney Children's Hospitals Network
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
Peter MacCallum Cancer Centre, Australia
Address [6] 0 0
Country [6] 0 0
Other collaborator category [7] 0 0
Other
Name [7] 0 0
University of Melbourne
Address [7] 0 0
Country [7] 0 0
Other collaborator category [8] 0 0
Other
Name [8] 0 0
Queensland Children's Hospital
Address [8] 0 0
Country [8] 0 0
Other collaborator category [9] 0 0
Other
Name [9] 0 0
Royal Adelaide Hospital
Address [9] 0 0
Country [9] 0 0
Other collaborator category [10] 0 0
Other
Name [10] 0 0
Pathology Queensland
Address [10] 0 0
Country [10] 0 0
Other collaborator category [11] 0 0
Government body
Name [11] 0 0
Royal Brisbane and Women's Hospital
Address [11] 0 0
Country [11] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/study/NCT06510699
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Jason A Roberts, PhD
Address 0 0
Country 0 0
Phone 0 0
+61 7 3346 5032
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06510699