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| ID | Type | Description | Link |
|---|---|---|---|
| 2024-A01425-42 | Other Identifier | ID RCB |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| individualized maintenance doses | Experimental | Individualization of first maintenance doses through a multiparametric algorithm integrating CYP2C19 genotype, C reactive protein level and age |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Individualization of first voriconazole maintenance doses | Drug | Individualization of first voriconazole maintenance doses |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of patients with initial plasma voriconazole trough concentration in the therapeutic range | Day 5 +/-2 |
| Measure | Description | Time Frame |
|---|---|---|
| Frequency of initial plasma voriconazole trough concentrations above the therapeutic range | Day 5 +/-2 | |
| Frequency of initial plasma voriconazole trough concentrations below the therapeutic range | Day 5 +/-2 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Gautier-Veyret Elodie, PharmD, PhD | Contact | +33476765492 | Egautier@chu-grenoble.fr | |
| Thiebaut-bertrand Anne, MD | Contact | Athiebaut@chu-grenoble.fr |
| Name | Affiliation | Role |
|---|---|---|
| Gautier-Veyret Elodie | Grenoble Alps University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Gautier-Veyret | Grenoble | 38043 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33217017 | Background | Gautier-Veyret E, Thiebaut-Bertrand A, Roustit M, Bolcato L, Depeisses J, Schacherer M, Schummer G, Fonrose X, Stanke-Labesque F. Optimization of voriconazole therapy for treatment of invasive aspergillosis: Pharmacogenomics and inflammatory status need to be evaluated. Br J Clin Pharmacol. 2021 Jun;87(6):2534-2541. doi: 10.1111/bcp.14661. Epub 2020 Dec 13. | |
| 34068031 |
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| ID | Term |
|---|---|
| D009181 | Mycoses |
| D019337 | Hematologic Neoplasms |
| ID | Term |
|---|---|
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| Voriconazole area under the curve (AUC0-12h) after the first maintenance dose individualized | Day 2 |
| Time to get the therapeutic range | through study completion, an average of 3 months |
| Treatment outcome in patients curatively treated | At month 3 +/- 15 days |
| Frequency of side effects | through study completion, an average of 3 months |
| Percentage of patients with initial plasma voriconazole trough concentration in the therapeutic range | comparison with an historic cohort | Day 5 +/-2 |
| Bolcato L, Khouri C, Veringa A, Alffenaar JWC, Yamada T, Naito T, Lamoureux F, Fonrose X, Stanke-Labesque F, Gautier-Veyret E. Combined Impact of Inflammation and Pharmacogenomic Variants on Voriconazole Trough Concentrations: A Meta-Analysis of Individual Data. J Clin Med. 2021 May 13;10(10):2089. doi: 10.3390/jcm10102089. |
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |