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Trial record 39 of 51 for:    "Invasive Aspergillosis" | "Anti-Infective Agents"

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

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ClinicalTrials.gov Identifier: NCT03067350
Recruitment Status : Completed
First Posted : March 1, 2017
Last Update Posted : February 18, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospital, Grenoble

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
Invasive Aspergillosis Haematological Cancer Patients Voriconazole

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.


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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 : January 2015
Actual Primary Completion Date : January 2019
Actual Study Completion Date : January 2019

Resource links provided by the National Library of Medicine





Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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. 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),



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Criteria

Inclusion Criteria:

  • patients suffering from haematological cancer

Exclusion Criteria:

  • less than 18-years old

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03067350


Locations
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France
University Hospital, Grenoble Alpes
Grenoble, France, 38043
Sponsors and Collaborators
University Hospital, Grenoble
Investigators
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Principal Investigator: Elodie GAUTIER University Hospital, Grenoble

Publications:

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Responsible Party: University Hospital, Grenoble
ClinicalTrials.gov Identifier: NCT03067350     History of Changes
Other Study ID Numbers: 38RC15.168
First Posted: March 1, 2017    Key Record Dates
Last Update Posted: February 18, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Anti-Infective Agents
Aspergillosis
Mycoses
Voriconazole
Antifungal Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors