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

Sponsor
University Hospital, Grenoble (Other)
Overall Status
Completed
CT.gov ID
NCT03067350
Collaborator
(none)
47
Enrollment
1
Location
48
Actual Duration (Months)
1
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase

    Detailed 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

    1. 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

    Study Type:
    Observational
    Actual Enrollment :
    47 participants
    Observational Model:
    Cohort
    Time Perspective:
    Prospective
    Official Title:
    Influence of a Combined Pharmacogenetic Score on Through Plasma Voriconazole Concentrations in Haematological Patients
    Actual Study Start Date :
    Jan 1, 2015
    Actual Primary Completion Date :
    Jan 1, 2019
    Actual Study Completion Date :
    Jan 1, 2019

    Outcome Measures

    Primary Outcome Measures

    1. number of initial voriconazole trough plasma concentration in the therapeutic range (1-4mg/l) [concentration measured between 5 to 10 days after voriconazole treatment initiation]

      Initial voriconazole trough plasma concentration

    Secondary Outcome Measures

    1. initial voriconazole trough plasma concentrations adjusted on the dose [concentration measured between 5 to 10 days after voriconazole treatment initiation]

      Initial voriconazole trough plasma concentration

    2. number of patients with therapeutic success [3 months after voriconazole therapy initiation]

      treatment outcome determined 3 months after voriconazole initiation (failure, stable response, success)

    3. number of patients with adverse effects [duration of voriconazole treatment (maximum length of follow-up : 3 months)]

      adverse effects include neurological disorders such as visual disturbance and/or hallucinations and hepatotoxicity (evaluated by ALAT/ASAT, bilirubin and γ-GT levels),

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • patients suffering from haematological cancer
    Exclusion Criteria:
    • less than 18-years old

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University Hospital, Grenoble Alpes Grenoble France 38043

    Sponsors and Collaborators

    • University Hospital, Grenoble

    Investigators

    • Principal Investigator: Elodie GAUTIER, University Hospital, Grenoble

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    University Hospital, Grenoble
    ClinicalTrials.gov Identifier:
    NCT03067350
    Other Study ID Numbers:
    • 38RC15.168
    First Posted:
    Mar 1, 2017
    Last Update Posted:
    Feb 18, 2019
    Last Verified:
    Feb 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by University Hospital, Grenoble
    voriconazole
    pharmacogenetics
    pharmacokinetics
    therapeutic drug monitoring
    Additional relevant MeSH terms:
    Aspergillosis

    Study Results

    No Results Posted as of Feb 18, 2019