Personalized Dosing for Fungal Infections

(PRAGMATIC Trial)

Recruiting at 6 trial locations

Overseen By Luminita Vlad

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: The University of Queensland

Must be taking: Voriconazole

Disqualifiers: Post-HCT without DNA, Imminent death, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 4 weeks

104 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of administering voriconazole, an antifungal medication, to individuals with blood cancer who have serious fungal infections. The goal is to determine if adjusting doses based on a genetic test and special software helps more patients receive the correct amount of medicine by day 8 compared to usual care. The study will also assess the practicality of this approach in real-world healthcare and its cost-effectiveness. Suitable participants include those with blood cancer already prescribed voriconazole. The trial consists of two groups: one receiving standard care and the other undergoing precision dosing with the new method. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It focuses on dosing voriconazole for fungal infections, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that voriconazole is likely to be safe for humans?

Research has shown that voriconazole is usually well-tolerated, though some people may experience side effects. In one study, about 18% of patients had treatment-related reactions. Another study found that adjusting doses based on therapeutic drug monitoring (TDM) can help manage safety. TDM involves checking drug levels in the blood to ensure they remain in the right range, which can better manage the risk of serious reactions.

Voriconazole is already used to treat fungal infections. This trial involves personalized dosing, aiming to enhance safety and effectiveness by tailoring treatment to individual needs. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about this trial because it explores a personalized approach to dosing voriconazole for fungal infections. Unlike standard methods, which adjust doses based on weight and routine drug monitoring, this approach incorporates genetic testing and advanced software to tailor dosages more precisely to each patient's unique profile. This could lead to more effective and safer treatments, reducing side effects and improving outcomes by ensuring patients receive the optimal dose faster.

What evidence suggests that voriconazole with precision dosing might be an effective treatment for fungal infections in blood cancer patients?

This trial will compare two approaches to voriconazole dosing for fungal infections. In the Standard Care arm, participants receive weight-based initial dosing of voriconazole, with dose adjustments based on standard therapeutic drug monitoring (TDM) and clinical judgment. In the Precision Care arm, participants also start with standard dosing, but their doses are adjusted using specialized software that incorporates TDM and genotype data. Research has shown that monitoring drug levels can help customize voriconazole treatment for each person. Studies have found that the amount of voriconazole in the blood is linked to treatment effectiveness. By using genetic testing, the dose can be adjusted to fit each patient, potentially improving results. Special tools and software help achieve the right drug levels more reliably. This personalized method aims to make voriconazole more effective against fungal infections, especially in patients with blood cancer. ^{2 6 7 8 9}

Who Is on the Research Team?

Jason A Roberts, PhD

Principal Investigator

The University of Queensland

Are You a Good Fit for This Trial?

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

Death is likely imminent within 7 days

Previously randomised to this trial

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline and Randomisation

Baseline data collection and randomisation of participants into standard care or precision care groups

1 week

1 visit (in-person)

Treatment

Participants receive voriconazole with dose adjustments based on TDM and genotype testing

4 weeks

Multiple visits for blood sampling and dose adjustments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Voriconazole

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.

How Is the Trial Designed?

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+

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+

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+

Published Research Related to This Trial

Voriconazole is an effective antifungal agent, showing at least equal efficacy to amphotericin B for treating acute invasive aspergillosis in immunocompromised patients, and similar effectiveness to fluconazole for esophageal candidiasis.

The drug is well-absorbed when taken orally and can penetrate the central nervous system, but it may cause side effects like visual disturbances and liver function test elevations, and it has potential drug interactions due to its metabolism through specific liver enzymes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Voriconazole: a new triazole antifungal agent. Pearson, MM., Rogers, PD., Cleary, JD., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8548711/

Predicting Voriconazole Outcome With PK/PD Model Therapeutic drug monitoring is considered to be an effective tool for the individualized use of voriconazole.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10520167/

Towards Model-Informed Precision Dosing of Voriconazole This approach aims to predict, individualize, and thereby optimize dosing and therapy outcomes based on patient characteristics and data from ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1198743X14617535

Voriconazole concentrations and outcome of invasive ... An association between poor outcome and voriconazole concentrations, varying from 0.25 to 2 mg/L, has been observed.

4. ascpt.onlinelibrary.wiley.com ascpt.onlinelibrary.wiley.com/doi/full/10.1111/cts.70317

CYP2C19‐Guided Voriconazole Therapy: A Precision ... The collected data included patient demographics, comorbidities, laboratory results, VRCZ dosage, duration, type of fungal infection, and ...

5. journals.asm.org journals.asm.org/doi/10.1128/AAC.02025-12

Software for Dosage Individualization of Voriconazole for ... We developed software to enable the individualization of voriconazole dosing to attain predefined serum concentration targets. The process of individualized ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3346940/

An observational efficacy and safety analysis of the ... Treatment-related adverse events were reported for 18% (22/119) of patients. This observational study confirms the results of previous clinical trials ...

7. bmcinfectdis.biomedcentral.com bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-017-2913-8

Meta-analysis of the safety of voriconazole in definitive ... The primary outcome was the proportion of patients who discontinued antifungal therapy due to adverse events. ... Another secondary outcome is ...

8. academic.oup.com academic.oup.com/cid/article/55/8/1080/339928

Effect of Therapeutic Drug Monitoring on Safety and Efficacy of ... Of 108 patients, overall mortality was 11 (20%) in the TDM group and 18 (34%) in the non-TDM group at 6 weeks after the initiation of voriconazole therapy and ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT00647907

A Study of the Efficacy and Safety of Voriconazole for ... Study Details | NCT00647907 | A Study of the Efficacy and Safety of Voriconazole for the Treatment of Fungal Infections | ClinicalTrials.gov.