Ignite Creation Date:
2025-12-24 @ 1:04 PM
Ignite Modification Date:
2025-12-28 @ 9:34 PM
Study NCT ID:
NCT02100761
Status:
UNKNOWN
Last Update Posted:
2014-04-01
First Post:
2014-03-03
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
CYP 2C19 Polymorphism and Voriconazole Trough Concentration in Chinese Adult Patients
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D055744', 'term': 'Invasive Pulmonary Aspergillosis'}], 'ancestors': [{'id': 'D055732', 'term': 'Pulmonary Aspergillosis'}, {'id': 'D001228', 'term': 'Aspergillosis'}, {'id': 'D009181', 'term': 'Mycoses'}, {'id': 'D001423', 'term': 'Bacterial Infections and Mycoses'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D000072742', 'term': 'Invasive Fungal Infections'}, {'id': 'D008172', 'term': 'Lung Diseases, Fungal'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D065819', 'term': 'Voriconazole'}], 'ancestors': [{'id': 'D014230', 'term': 'Triazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'The susceptibility test of aspergillosis strains to voriconazole, serum galactomannan (GM) test, voriconazole trough levels and genotyping of CYP2C19 will be measured.'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'CASE_ONLY'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 200}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2014-06'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2014-03', 'completionDateStruct': {'date': '2015-06', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2014-03-31', 'studyFirstSubmitDate': '2014-03-03', 'studyFirstSubmitQcDate': '2014-03-31', 'lastUpdatePostDateStruct': {'date': '2014-04-01', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2014-04-01', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2015-06', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'voriconazole trough level', 'timeFrame': 'one year'}], 'secondaryOutcomes': [{'measure': 'Overall mortality', 'timeFrame': 'one year'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Voriconazole', 'Invasive pulmonary aspergillosis', 'Therapeutic drug monitoring', 'CYP genetic polymorphism', 'Efficacy', 'Safety'], 'conditions': ['Invasive Pulmonary Aspergillosis']}, 'descriptionModule': {'briefSummary': 'To investigate the relationship between cytochrome P450 (CYP) 2C19 genetic polymorphism and the steady-state blood concentration of voriconazole in Chinese patients with invasive pulmonary aspergillosis (IPA), and to assess the effects of voriconazole trough concentration on the prognosis of IPA patients.', 'detailedDescription': 'Each isolate of aspergillosis will be recovered from clinical specimens (sputum, bronchoalveolar lavage fluid, lung biopsy tissue) and the identification of species level will also be performed in Qilu Hospital by using conventional methods (both macroscopic and microscopic characteristics). The aspergillosis strains will be stored in 10 % glycerol broth at -80 °C. The in vitro antifungal susceptibility test of aspergillosis strains to voriconazole will be performed in the Centre for Medical Mycology and Mycoses, First Hospital, Peking University, and the performance will be according to the Clinical and Laboratory Standards Institute (CLSI) standard M38-A2 microdilution methods.\n\nSerum galactomannan (GM) test will be performed twice per week for the first two weeks. A double-sandwich ELISA GM assay was used. A cut-off of optical density index (ODI) \\>0.5 was taken as positive.\n\nVoriconazole serum levels will be measured on day 4, day 7, day 10, and day 14 (all trough levels). In brief, quantitative analysis of voriconazole was performed using high-performance liquid chromatography coupled with tandem mass spectrometry.\n\nGenotyping of CYP2C19 will be performed using 3 ml of peripheral blood sampled into EDTA (ethylenediaminetetraacetic acid) tubes at day 4. Genomic DNA was extracted from blood leukocytes with the use of a DNA extraction kit. Genotyping was confirmed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis. Individuals can be divided into three groups according to the CYP2C19 genotype. Those who inherit two mutant CYP2C19 alleles (\\*2 and/or \\*3) have a reduced capacity to metabolize CYP2C19 substrates and are defined as poor metabolizers (PMs). Individuals who are homozygous (\\*1/\\*1) for wild-type CYP2C19\\*1 or 1 wild-type allele and 1 CY¬P2C19\\*17 have efficient enzymes to metabolize CYP2C19 substrates and are defined as extensive metabolizers (EMs). Subjects who are heterozygous (\\*1/\\*2, \\*1/\\*3) for wild-type CYP2C19\\*1 are defined as intermediate metabolizers (IMs)'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '18 Years', 'samplingMethod': 'PROBABILITY_SAMPLE', 'studyPopulation': 'Patients with invasive pulmonary aspergillosis and will be treated with voriconazole according to their physician decision', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Proven, probable, or possible invasive pulmonary aspergillosis (IPA)\n* Acute IPA defined as duration of clinical syndrome of \\<30 days.\n* Treatment with voriconazole\n* At least 18 years and older\n* Weight \\>40 kg and ≤120 kg\n* Given the informed consent\n\nExclusion Criteria:\n\n* Patients allergic to azole(s)\n* Patients who heve been prescribed voriconazole before\n* Positive urine pregnancy test (if female)\n* Patients with aspergilloma or chronic aspergillosis ( \\>1 month duration )\n* Anticipated survival of less than 5 days or Karnofsky score \\<=20'}, 'identificationModule': {'nctId': 'NCT02100761', 'briefTitle': 'CYP 2C19 Polymorphism and Voriconazole Trough Concentration in Chinese Adult Patients', 'organization': {'class': 'OTHER', 'fullName': 'Qilu Hospital of Shandong University'}, 'officialTitle': 'Impact of Cytochrome P450 2C19 Genotype Polymorphism on Voriconazole Trough Concentration in Chinese Adult Patients With Invasive Pulmonary Aspergillosis: a Prospective Multicenter Research', 'orgStudyIdInfo': {'id': 'KYLL-2014(KS)-085'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'invasive pulmonary aspergillosis', 'description': 'Patients with invasive pulmonary aspergillosis and will be treated with voriconazole according to their physician decision in five hospital, Jinan, China', 'interventionNames': ['Drug: Voriconazole']}], 'interventions': [{'name': 'Voriconazole', 'type': 'DRUG', 'otherNames': ['Voriconazole Intravenous Solution 200 mg', 'Voriconazole Tablet 50 mg / Voriconazole Tablet 200 mg'], 'description': 'Patients with creatinine clearance at least 50 ml/min will be treated with voriconazole by intravenous drip infusion at the dose of 6 mg/kg twice daily on the first day (Day 1) and 4 mg/kg twice daily from day 2 onward. The IV treatment is at least 7 days. Then switch to 200 mg orally twice daily between meals. The total treatment duration is at least 14 days Patients with creatinine clearance \\<50 ml/min will be treated with oral voriconazole (loading dose of 400 mg twice daily followed by maintenance dose of 200 mg twice daily between meals for at least 14.0 days).', 'armGroupLabels': ['invasive pulmonary aspergillosis']}]}, 'contactsLocationsModule': {'locations': [{'zip': '250012', 'city': 'Jinan', 'state': 'Shandong', 'country': 'China', 'contacts': [{'name': 'Shifang Ding, Ph.D.', 'role': 'CONTACT', 'email': 'dingshifang@sdu.edu.cn', 'phone': '18560081003', 'phoneExt': '+86'}, {'name': 'Shifang Ding, Ph.D.', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Qilu Hospital', 'geoPoint': {'lat': 36.66833, 'lon': 116.99722}}], 'centralContacts': [{'name': 'Shifang Ding, Ph.D.', 'role': 'CONTACT', 'email': 'dingshifang@sdu.edu.cn', 'phone': '18560081003', 'phoneExt': '+86'}], 'overallOfficials': [{'name': 'Shifang Ding, Ph.D.', 'role': 'STUDY_CHAIR', 'affiliation': 'Qilu Hospital of Shandong University'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'dingshifang', 'class': 'OTHER'}, 'collaborators': [{'name': 'Shandong Provincial Hospital', 'class': 'OTHER_GOV'}, {'name': 'Qianfoshan Hospital', 'class': 'OTHER'}, {'name': 'Shandong thorax hospital', 'class': 'UNKNOWN'}, {'name': 'Jinan Military General Hospital', 'class': 'OTHER'}, {'name': 'Jinan Central Hospital', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'Professor', 'investigatorFullName': 'dingshifang', 'investigatorAffiliation': 'Qilu Hospital of Shandong University'}}}}