Ignite Creation Date:
2025-12-24 @ 5:23 PM
Ignite Modification Date:
2026-04-08 @ 11:08 AM
Study NCT ID:
NCT03067350
Status:
COMPLETED
Last Update Posted:
2019-02-18
First Post:
2017-02-06
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Influence of a Combined Pharmacogenetic Score on Through Plasma Voriconazole Concentrations in Haematological Patients
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 47}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2015-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2019-02', 'completionDateStruct': {'date': '2019-01', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2019-02-15', 'studyFirstSubmitDate': '2017-02-06', 'studyFirstSubmitQcDate': '2017-02-28', 'lastUpdatePostDateStruct': {'date': '2019-02-18', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2017-03-01', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2019-01', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'number of initial voriconazole trough plasma concentration in the therapeutic range (1-4mg/l)', 'timeFrame': 'concentration measured between 5 to 10 days after voriconazole treatment initiation', 'description': 'Initial voriconazole trough plasma concentration'}], 'secondaryOutcomes': [{'measure': 'initial voriconazole trough plasma concentrations adjusted on the dose', 'timeFrame': 'concentration measured between 5 to 10 days after voriconazole treatment initiation', 'description': 'Initial voriconazole trough plasma concentration'}, {'measure': 'number of patients with therapeutic success', 'timeFrame': '3 months after voriconazole therapy initiation', 'description': 'treatment outcome determined 3 months after voriconazole initiation (failure, stable response, success)'}, {'measure': 'number of patients with adverse effects', 'timeFrame': 'duration of voriconazole treatment (maximum length of follow-up : 3 months)', 'description': 'adverse effects include neurological disorders such as visual disturbance and/or hallucinations and hepatotoxicity (evaluated by ALAT/ASAT, bilirubin and γ-GT levels),'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['voriconazole', 'pharmacogenetics', 'pharmacokinetics', 'therapeutic drug monitoring'], 'conditions': ['Invasive Aspergillosis', 'Haematological Cancer Patients', 'Voriconazole']}, 'referencesModule': {'references': [{'pmid': '25645831', 'type': 'BACKGROUND', 'citation': 'Gautier-Veyret E, Fonrose X, Tonini J, Thiebaut-Bertrand A, Bartoli M, Quesada JL, Bulabois CE, Cahn JY, Stanke-Labesque F. Variability of voriconazole plasma concentrations after allogeneic hematopoietic stem cell transplantation: impact of cytochrome p450 polymorphisms and comedications on initial and subsequent trough levels. Antimicrob Agents Chemother. 2015 Apr;59(4):2305-14. doi: 10.1128/AAC.04838-14. Epub 2015 Feb 2.'}, {'pmid': '27318623', 'type': 'BACKGROUND', 'citation': 'Gautier-Veyret E, Fonrose X, Stanke-Labesque F. A genetic score combining CYP450 2C19 and 3A4 genotypes to predict voriconazole plasma exposure? Int J Antimicrob Agents. 2016 Aug;48(2):221-2. doi: 10.1016/j.ijantimicag.2016.05.002. Epub 2016 Jun 7. No abstract available.'}, {'pmid': '26384041', 'type': 'BACKGROUND', 'citation': 'Tonini J, Bailly S, Gautier-Veyret E, Wambergue C, Pelloux H, Thiebaut-Bertrand A, Cornet M, Stanke-Labesque F, Maubon D. Contribution of a Simple Bioassay in Effective Therapeutic Drug Monitoring of Posaconazole and Voriconazole. Ther Drug Monit. 2015 Oct;37(5):685-8. doi: 10.1097/FTD.0000000000000199.'}, {'pmid': '22850515', 'type': 'BACKGROUND', 'citation': 'Tonini J, Thiebaut A, Jourdil JF, Berruyer AS, Bulabois CE, Cahn JY, Stanke-Labesque F. Therapeutic drug monitoring of posaconazole in allogeneic hematopoietic stem cell transplantation patients who develop gastrointestinal graft-versus-host disease. Antimicrob Agents Chemother. 2012 Oct;56(10):5247-52. doi: 10.1128/AAC.00815-12. Epub 2012 Jul 30.'}, {'pmid': '23384531', 'type': 'BACKGROUND', 'citation': 'Jourdil JF, Tonini J, Stanke-Labesque F. Simultaneous quantitation of azole antifungals, antibiotics, imatinib, and raltegravir in human plasma by two-dimensional high-performance liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Mar 1;919-920:1-9. doi: 10.1016/j.jchromb.2012.12.028. Epub 2013 Jan 9.'}]}, 'descriptionModule': {'briefSummary': '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.\n\nMain Objective: To determine predictive value of a combined pharmacogenetic score on onset of trough voriconazole plasma concentration inferior than lower therapeutic target.', 'detailedDescription': '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.\n\nThe 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'patients suffering from haematological cancer Followed at the hematolofic clinic of Grenoble University Hospital Starting treatment by voriconazole whatever the route of administration', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* patients suffering from haematological cancer\n\nExclusion Criteria:\n\n* less than 18-years old'}, 'identificationModule': {'nctId': 'NCT03067350', 'acronym': 'VORIGENE', 'briefTitle': 'Influence of a Combined Pharmacogenetic Score on Through Plasma Voriconazole Concentrations in Haematological Patients', 'organization': {'class': 'OTHER', 'fullName': 'University Hospital, Grenoble'}, 'officialTitle': 'Influence of a Combined Pharmacogenetic Score on Through Plasma Voriconazole Concentrations in Haematological Patients', 'orgStudyIdInfo': {'id': '38RC15.168'}}, 'contactsLocationsModule': {'locations': [{'zip': '38043', 'city': 'Grenoble', 'country': 'France', 'facility': 'University Hospital, Grenoble Alpes', 'geoPoint': {'lat': 45.17869, 'lon': 5.71479}}], 'overallOfficials': [{'name': 'Elodie GAUTIER', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University Hospital, Grenoble'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University Hospital, Grenoble', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}