Related Experiment Video
Updated: Dec 7, 2025
Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance
Published on: December 28, 2017
Randomised multicentre clinical trial to evaluate voriconazole pre-emptive genotyping strategy in patients with risk
Jaime Monserrat Villatoro1, Irene García García1, David Bueno2
1Clinical Pharmacology Department, Hospital Universitario La Paz IdiPAZ, Madrid, Spain.
Introduction:
Invasive aspergillosis is the most important cause of morbidity and mortality in patients with haematological diseases. At present, voriconazole is the first-line treatment for invasive fungal disease. The pharmacokinetic interindividual variability of voriconazole depends on genetic factors. CYP450 is involved in 70%-75% of total metabolism of voriconazole, mainly CYP3A4 and CYP2C19, with the remaining 25%-30% of metabolism conducted by monooxygenase flavins. CYP2C19 single nucleotide polymorphisms could explain 50%-55% of variability in voriconazole metabolism.
Materials And Methods:
The main objective is to compare efficiency of pre-emptive voriconazole genotyping with routine practice. The primary outcome is serum voriconazole on the fifth day within the therapeutic range. The secondary outcome is the combined variables of therapeutic failure and adverse events within 90 days of first administration, associated with voriconazole. A total of 146 patients at risk of invasive aspergillosis who will potentially receive voriconazole will be recruited, and CYP2C19 will be genotyped. If the patient ultimately receives voriconazole, they will be randomised (1:1 experimental/control). In the experimental arm, patients will receive a dose according to a pharmacogenetic algorithm, including CYP2C19 genotype and clinical and demographic information. In the control arm, patients will receive a dose according to clinical practice guidelines. In addition, a Spanish National Healthcare System (NHS) point-of-view cost-effectiveness evaluation will be performed. Direct cost calculations for each arm will be performed.
Conclusion:
This trial will provide information about the viability and cost-effectiveness of the implementation of a pre-emptive voriconazole genotyping strategy in the Spanish NHS.
Ethics And Dissemination:
A Spanish version of this protocol has been evaluated and approved by the La Paz University Hospital Ethics Committee and the Spanish Agency of Medicines and Medical Devices. Trial results will be submitted for publication in an open peer-reviewed medical speciality-specific publication.
Trial Registration Number:
Eudra-CT: 2019-000376-41 and NCT04238884; Pre-results.
Insights
This study investigates using CYP2C19 genotyping to optimize voriconazole dosing for invasive aspergillosis in hematology patients. Pharmacogenetic algorithms may improve therapeutic drug monitoring and patient outcomes.
Area of Science:
- Pharmacogenomics
- Clinical Pharmacology
- Infectious Diseases
Background:
- Invasive aspergillosis poses significant risks for hematology patients.
- Voriconazole is a primary treatment, but its efficacy is limited by inter-individual pharmacokinetic variability.
- CYP2C19 genetic polymorphisms are key determinants of voriconazole metabolism, influencing treatment outcomes.
Purpose of the Study:
- To compare the efficacy of pre-emptive voriconazole genotyping versus standard practice in achieving therapeutic drug levels.
- To evaluate the impact of genotype-guided dosing on treatment failure and adverse events.
- To assess the cost-effectiveness of implementing a pharmacogenetic strategy within the Spanish National Healthcare System.
Main Methods:
- A randomized controlled trial involving 146 patients at risk for invasive aspergillosis.
- Patients receiving voriconazole will be randomized to receive dosing based on a pharmacogenetic algorithm (including CYP2C19 genotype) or standard clinical guidelines.
- Primary outcome: serum voriconazole levels on day 5. Secondary outcomes: therapeutic failure and adverse events within 90 days.
Main Results:
- The study aims to provide data on the clinical utility and cost-effectiveness of pre-emptive CYP2C19 genotyping for voriconazole therapy.
- Results will inform the potential implementation of pharmacogenetic-guided dosing in routine clinical practice.
Conclusions:
- Pre-emptive voriconazole genotyping may offer a viable strategy to optimize treatment in at-risk patient populations.
- This approach has the potential to improve therapeutic outcomes and manage healthcare costs effectively.
Related Concept Videos
01:11Clinical Trials: Overview
01:16Clinical Trials
There are four phases in a clinical trial. A phase one...
01:15Bioavailability Study Design: Healthy Subjects Versus Patients
01:11Bioavailability Study Design: Single Versus Multiple Dose Studies