An observational study in Invasive Aspergillosis, Haematological Cancer Patients and Voriconazole, sponsored by University Hospital, Grenoble. Completed at 1 site in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-02-18.
Sponsored by University Hospital, Grenoble · Observational
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.
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.
201 studies on the registry are indexed under Aspergillosis; 22 are open to participants now.
This study's enrollment of 47 is below the median of 150 across 81 observational studies indexed under Aspergillosis.
Browse Aspergillosis studies →University Hospital, Grenoble is the lead sponsor of 815 studies on the registry; 205 are open to participants now.
Counted across the registry records on this site, refreshed daily.
patients suffering from haematological cancer Followed at the hematolofic clinic of Grenoble University Hospital Starting treatment by voriconazole whatever the route of administration
Exclusion Criteria:
number of initial voriconazole trough plasma concentration in the therapeutic range (1-4mg/l)
Initial voriconazole trough plasma concentration
Time frame: concentration measured between 5 to 10 days after voriconazole treatment initiation
initial voriconazole trough plasma concentrations adjusted on the dose
Initial voriconazole trough plasma concentration
Time frame: concentration measured between 5 to 10 days after voriconazole treatment initiation
number of patients with therapeutic success
treatment outcome determined 3 months after voriconazole initiation (failure, stable response, success)
Time frame: 3 months after voriconazole therapy initiation
number of patients with adverse effects
adverse effects include neurological disorders such as visual disturbance and/or hallucinations and hepatotoxicity (evaluated by ALAT/ASAT, bilirubin and γ-GT levels),
Time frame: duration of voriconazole treatment (maximum length of follow-up : 3 months)
Plan to share: No
This study is completed, as verified in Feb 2019. You cannot join it, but the record below documents what was studied.
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University Hospital, Grenoble