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

February 15, 2019 updated by: University Hospital, Grenoble

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.

Study Overview

Status

Completed

Conditions

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 >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 Type

Observational

Enrollment (Actual)

47

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Grenoble, France, 38043
        • University Hospital, Grenoble Alpes

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

patients suffering from haematological cancer Followed at the hematolofic clinic of Grenoble University Hospital Starting treatment by voriconazole whatever the route of administration

Description

Inclusion Criteria:

  • patients suffering from haematological cancer

Exclusion Criteria:

  • less than 18-years old

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
number of initial voriconazole trough plasma concentration in the therapeutic range (1-4mg/l)
Time Frame: concentration measured between 5 to 10 days after voriconazole treatment initiation
Initial voriconazole trough plasma concentration
concentration measured between 5 to 10 days after voriconazole treatment initiation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
initial voriconazole trough plasma concentrations adjusted on the dose
Time Frame: concentration measured between 5 to 10 days after voriconazole treatment initiation
Initial voriconazole trough plasma concentration
concentration measured between 5 to 10 days after voriconazole treatment initiation
number of patients with therapeutic success
Time Frame: 3 months after voriconazole therapy initiation
treatment outcome determined 3 months after voriconazole initiation (failure, stable response, success)
3 months after voriconazole therapy initiation
number of patients with adverse effects
Time Frame: 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),
duration of voriconazole treatment (maximum length of follow-up : 3 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Grenoble

Investigators

  • Principal Investigator: Elodie GAUTIER, University Hospital, Grenoble

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2015

Primary Completion (Actual)

January 1, 2019

Study Completion (Actual)

January 1, 2019

Study Registration Dates

First Submitted

February 6, 2017

First Submitted That Met QC Criteria

February 28, 2017

First Posted (Actual)

March 1, 2017

Study Record Updates

Last Update Posted (Actual)

February 18, 2019

Last Update Submitted That Met QC Criteria

February 15, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 38RC15.168

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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