Influence of a Combined Pharmacogenetic Score on Through Plasma

Status Completed

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

Clinical Trial Details

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

View Details

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

Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.

Phase 1: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase 2: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
Phase 3: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
Phase 4: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.

Influence of a Combined Pharmacogenetic Score on Through Plasma Voriconazole Concentrations in Haematological Patients — VORIGENE

Clinical Trial Summary

Clinical Trial Description

Study Design

Related Conditions & MeSH terms