Individualized First Maintenance Doses of Voriconazole Through a Multiparametric Algorithm (VORIPRECI)

Grenoble Alpes University Hospital Center (CHU)

Status and phase

Not yet enrolling

Phase 4

Conditions

Hematologic Malignancy

Fungal Infection

Aspergillosis Invasive

Study type

Interventional

Funder types

Other

Identifiers

NCT06582186

38RC23.0230

Details and patient eligibility

About

The goal of this interventional single-arm study is to evaluate the interest of a multiparametric algorithm for individualization of first voriconazole maintenance doses for improvement of initial voriconazole exposure in adult patients with haematological malignancies. The main objective it aims is to determine the percentage of patients with initial voriconazole trough concentrations in the therapeutic range after individualization of first maintenance doses.

Participants will benefited from individualization of first voriconazole maintenance doses through a previously developed and validated multiparametric algorithm (publication in progress) taking into account CYP2C19 genotype, C reactive protein level and age.

Full description

The currently recommended therapeutic drug monitoring of voriconazole has improved the efficacy of this treatment and reduced its adverse effects, especially for treatment and prophylaxis of invasive aspergillosis. However, dose adjustments made as part of this therapeutic drug monitoring only occur at the earliest 3 to 5 days after the initiation of treatment, whereas it is essential to achieve effective concentrations from the start of treatment. Simple a priori dose adjustment approaches based on CYP2C19 genotype have been shown to improve voriconazole exposure and treatment response. However other factors such as the patient's inflammatory status or age also influence voriconazole exposure, suggesting that strategies for individualizing initial voriconazole doses could be improved by integrating all covariates influencing voriconazole pharmacokinetics. In this line, a previous multicenter and international study has developped and validated an algorithm for calculating the first maintenance doses integrating not only the CYP2C19 genotype, but also the inflammatory status, the patient's age, and the presence (or not) of hematological malignancy. Here, the investigators propose to evaluate the interest of this multiparametric algorithm for improving initial exposure (within the first 4 days) to voriconazole in patients suffering from haematological malignancies.

Enrollment

30 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

adult patient suffering from haematological malignancy
followed in the clinical hematology department or in the hematology day hospital of the Grenoble Alps University Hospital
consenting to carrying out CYP2C19 genotyping
likely to start treatment with voriconazole (for curative or prophylactic purposes as part of care)
having signed a written consent to participate
affiliated to a social security system

Exclusion criteria

comedication with strong inhibitors/inducers (valproic acid, phenytoin, carbamazepine, rifampicin)
Subject during exclusion period from another study,
Persons referred to in articles L1121-5 to L1121-8 of the CSP (corresponds to all protected persons: pregnant woman, parturient woman, breastfeeding mother, person deprived of liberty by judicial or administrative decision, persons subject to care psychiatric pursuant to articles L. 3212-1 and L. 3213-1 who do not fall under the provisions of article L. 1121-8, persons admitted to a health or social establishment for purposes other than research , minors, person subject to a legal protection measure or unable to express their consent)