Clinical Trials Logo

Clinical Trial Summary

Hypothesis: A pharmacogenetic score integrating both CYP3A genotypes could be influence initial trough voriconazole plasma concentrations and thus useful to adapt a priori voriconazole dosing in order to get adequate voriconazole exposure as possible after starting treatment.

Main Objective: To determine predictive value of a combined pharmacogenetic score on onset of trough voriconazole plasma concentration inferior than lower therapeutic target.


Clinical Trial Description

Voriconazole (VRC), the gold-standard treatment of invasive aspergillosis is characterized by variables and nonlinear pharmacokinetics, causing many under- or over-dosing. A link exist between trough plasma concentrations (Cmin) of VRC and effectiveness but also its toxicity. Thus the longitudinal therapeutic drug monitoring of VRC is now recommended with a therapeutic range between 1 and 5 mg/L. The pharmacokinetic variability of VRC is in part explained by its metabolism, mainly dependent on cytochrome P 450 (CYP), particularly CYP2C19, 3A4, 3A5; all these CYP exhibiting genetic polymorphisms. The authors, recently shown, and for the first time , in a retrospective study conducted in 29 patients allogeneic hematopoietic stem cell that initial VRC Cmin adjusted the dose was not only influenced by the route of administration but also by a pharmacogenetics score whose determination is to assign each genotype CYP2C19 and CYP3A a score expressed in a arbitrary units.

The combined pharmacogenetic score was strongly correlated with the original Cmin (r= -0.748; p = 0.002) and was the only independent predictor of initial Cmin (after adjusting the dose and the route of administration). In addition, none of the patients having a genetic score <2 (ie metabolizing capacity of reduced VRC) did not show an initial Cmin below 1 mg/L, while the initial Cmin was below this threshold efficiency in 47% of patients with a genetic score >2. The aim of this new study is to confirm the impact of the pharmacogenetic score on the initial VRC Cmin over a larger prospective cohort of 60 adult patients with onco-hematological diseases. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT03067350
Study type Observational
Source University Hospital, Grenoble
Contact
Status Completed
Phase
Start date January 2015
Completion date January 2019

See also
  Status Clinical Trial Phase
Recruiting NCT06028451 - ManagemEnt of Antifungal Drug in Invasive Aspergillosis:a Real-word Study
Completed NCT00163722 - A Multicentre Randomised Controlled Trial Comparing Two Strategies for the Diagnosis of Invasive Aspergillosis in High-risk Haematology Patients Phase 3
Completed NCT02394483 - Single Ascending Oral Dose Study of F901318 Phase 1
Completed NCT01128907 - Galactomannan Antigen in Bronchoalveolar Lavage in the Diagnosis of Invasive Aspergillosis in Neutropenic Patients N/A
Completed NCT00404092 - Caspofungin Maximum Tolerated Dose in Patients With Invasive Aspergillosis Phase 2
Recruiting NCT01386437 - Natural History of Individuals With Immune System Problems That Lead to Fungal Infections
Withdrawn NCT02912026 - Radiolabelled IV and Oral Metabolism Study of F901318 Phase 1
Withdrawn NCT03095547 - Drug/Drug Interactions With F901318 Phase 1
Withdrawn NCT03076905 - Pharmacokinetics of IV Formulation Phase 1
Completed NCT02737371 - Multiple Ascending Oral Dose Study of F901318 in Healthy Subjects Phase 1
Terminated NCT00836875 - A Study To Evaluate The Safety Of Voriconazole As Treatment Of Invasive Aspergillosis (Fungal Infection) And Other Rare Molds In Children Phase 3
Active, not recruiting NCT00838643 - Invasive Aspergillosis After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) N/A
Terminated NCT04876716 - Azole-echinocandin Combination Therapy for Invasive Aspergillosis Phase 3
Recruiting NCT05101187 - Olorofim Aspergillus Infection Study Phase 3
Enrolling by invitation NCT02104479 - Diagnostic Accuracy of Pleural Effusion Aspergillosis Biomarker Testing
Not yet recruiting NCT05707832 - A Study of ABCD for Injection in Subjects With Invasive Candidiasis and Invasive Aspergillus Phase 3
Recruiting NCT06382922 - Role of Antifungal Prophylaxis in Elderly Patients With Acute Myeloid Leukemia During Consolidation Therapy
Terminated NCT02396225 - Concentrations of Voriconazole in Blood and BAL-fluid After Inhalation and Oral Administration N/A
Recruiting NCT00843804 - Surveillance for Nosocomial Infections in Pediatric Cancer Patients N/A
Completed NCT00334412 - COMBISTRAT: AmBisome® in Combination With Caspofungin for the Treatment of Invasive Aspergillosis Phase 4