Ignite Creation Date:
2024-10-26 @ 3:35 PM
Last Modification Date:
2024-10-26 @ 3:35 PM
Study NCT ID:
NCT06510699
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-07-14
Brief Title:
Pharmacogenomics for Better Treatment of Fungal Infections in Cancer
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Randomized Clinical Trial to Evaluate the Use of Genotype-based Dosing of Voriconazole in Patients With Haematological Malignancy
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PRAGMATIC
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
Detailed Description:
Participants will be randomly assigned to standard care or precision care Current standard of care at trial-site institutions uses weight-based mgkg 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 software that includes patient data TDM and genotype data
Trial procedures following baseline data collection and randomisation genotype testing will be performed on Day 1 The precision care group have dose adjustment performed on Days 5 9 15 and 22 using genotype andor TDM results in dosing software The standard care group will have TDM performed and dose adjustments in accordance with usual clinical practice Blood sampling for TDM will be performed 24-hours prior to dose adjustment with additional blood samples collected on Days 1 and 2 in both standard care and precision care groups All blood sampling genotype testing and dose adjustments will be performed - day to support feasibility
The primary objective is to compare the proportion of patients achieving therapeutic voriconazole exposure at Day 8 when using precision care compared to standard care
Secondary objectives are
1 Clinical comparison of clinical success of voriconazole treatment between precision care and standard care groups where clinical success is defined as an absence of clinical deterioration or event that requires a change of therapy
2 Antifungal exposure to compare antifungal exposure over the first 28 days of therapy between precision care and standard care groups
3 Comparative precision care methodologies compare if there is a difference in daily dose recommendations between using a genotype nomogram dosing software with TDM or a combination of dose adjustment in precision care
4 Feasibility of precision care interventions to determine if it is feasible to perform the measurement of voriconazole concentrations and genotype testing for use in dosing software in time to intervene prior to Day 5 andor Day 9 dose adjustment
5 Genotype describe clinical success of voriconazole between genotypes
The implementation feasibility sub-study will assess the scalability of precision care to support optimal voriconazole dosing by tailoring the intervention to each trial setting and measuring outcomes with the involvement of key stakeholders end-users health administrators consumers community members
Data will be collected to ascertain Fidelity including 1 assess barriers and enablers 2 identify prioritise the factors influencing delivery and tailor these to fit local settings 3 assess intended fidelity to the precision care intervention
Data will be collected to ascertain Feasibility or the extent to which precision care can be successfully used in each study setting via completion of the feasibility implementation measure FIM at baselines and quarterly thereafter including qualitative interviews at the end of the study
Data will be collected to ascertain Acceptability or whether end-users perceive precision care as agreeable or satisfactory by survey and qualitative interviews with pharmacists physicians and health administrators
Data will be collected to undertake an economic evaluation to determine the cost-effectiveness of precision versus standard care exploring individual level data incremental cost effectiveness ratios ICERs at day 14 and 30 and cost-utility analysis to demonstrate if precision care offers value for money at Day 30 in the Australian setting The health economic evaluation will include use of surveys to capture 1 healthcare usage of trial participants 2 implementation feasibility measures and 3 implementation costs
Data will be collected to ascertain scalability or the ability to expand the efficacy of precision care on a small scale in controlled conditions to real world conditions to a greater proportion of the population
Therapeutic trough voriconazole exposures concentrations In this trial serum concentrations 1 mgL minimum effective concentration and 5 mgL maximum safe concentration are defined as the therapeutic range Treating clinicians may nominate an individualised patient target within this range prior to randomisation and that range will be applied during the trial Where dosing software is being applied the software will be programmed to target 25 mgL
Trial procedures following baseline data collection and randomisation genotype testing will be performed on Day 1 The precision care group have dose adjustment performed on Days 5 9 15 and 22 using genotype andor TDM results in dosing software The standard care group will have TDM performed and dose adjustments in accordance with usual clinical practice Blood sampling for TDM will be performed 24-hours prior to dose adjustment with additional blood samples collected on Days 1 and 2 in both standard care and precision care groups All blood sampling genotype testing and dose adjustments will be performed - day to support feasibility
The primary objective is to compare the proportion of patients achieving therapeutic voriconazole exposure at Day 8 when using precision care compared to standard care
Secondary objectives are
1 Clinical comparison of clinical success of voriconazole treatment between precision care and standard care groups where clinical success is defined as an absence of clinical deterioration or event that requires a change of therapy
2 Antifungal exposure to compare antifungal exposure over the first 28 days of therapy between precision care and standard care groups
3 Comparative precision care methodologies compare if there is a difference in daily dose recommendations between using a genotype nomogram dosing software with TDM or a combination of dose adjustment in precision care
4 Feasibility of precision care interventions to determine if it is feasible to perform the measurement of voriconazole concentrations and genotype testing for use in dosing software in time to intervene prior to Day 5 andor Day 9 dose adjustment
5 Genotype describe clinical success of voriconazole between genotypes
The implementation feasibility sub-study will assess the scalability of precision care to support optimal voriconazole dosing by tailoring the intervention to each trial setting and measuring outcomes with the involvement of key stakeholders end-users health administrators consumers community members
Data will be collected to ascertain Fidelity including 1 assess barriers and enablers 2 identify prioritise the factors influencing delivery and tailor these to fit local settings 3 assess intended fidelity to the precision care intervention
Data will be collected to ascertain Feasibility or the extent to which precision care can be successfully used in each study setting via completion of the feasibility implementation measure FIM at baselines and quarterly thereafter including qualitative interviews at the end of the study
Data will be collected to ascertain Acceptability or whether end-users perceive precision care as agreeable or satisfactory by survey and qualitative interviews with pharmacists physicians and health administrators
Data will be collected to undertake an economic evaluation to determine the cost-effectiveness of precision versus standard care exploring individual level data incremental cost effectiveness ratios ICERs at day 14 and 30 and cost-utility analysis to demonstrate if precision care offers value for money at Day 30 in the Australian setting The health economic evaluation will include use of surveys to capture 1 healthcare usage of trial participants 2 implementation feasibility measures and 3 implementation costs
Data will be collected to ascertain scalability or the ability to expand the efficacy of precision care on a small scale in controlled conditions to real world conditions to a greater proportion of the population
Therapeutic trough voriconazole exposures concentrations In this trial serum concentrations 1 mgL minimum effective concentration and 5 mgL maximum safe concentration are defined as the therapeutic range Treating clinicians may nominate an individualised patient target within this range prior to randomisation and that range will be applied during the trial Where dosing software is being applied the software will be programmed to target 25 mgL
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None