CYP 2C19 Polymorphism and Voriconazole Trough Concentration in Chinese Adult Patients
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|ClinicalTrials.gov Identifier: NCT02100761|
Recruitment Status : Unknown
Verified March 2014 by dingshifang, Qilu Hospital of Shandong University.
Recruitment status was: Not yet recruiting
First Posted : April 1, 2014
Last Update Posted : April 1, 2014
|Condition or disease||Intervention/treatment|
|Invasive Pulmonary Aspergillosis||Drug: Voriconazole|
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.
Serum 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.
Voriconazole 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.
Genotyping 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)
|Study Type :||Observational|
|Estimated Enrollment :||200 participants|
|Official Title:||Impact of Cytochrome P450 2C19 Genotype Polymorphism on Voriconazole Trough Concentration in Chinese Adult Patients With Invasive Pulmonary Aspergillosis: a Prospective Multicenter Research|
|Study Start Date :||June 2014|
|Estimated Primary Completion Date :||June 2015|
|Estimated Study Completion Date :||June 2015|
invasive pulmonary aspergillosis
Patients with invasive pulmonary aspergillosis and will be treated with voriconazole according to their physician decision in five hospital, Jinan, China
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).
- voriconazole trough level [ Time Frame: one year ]
- Overall mortality [ Time Frame: one year ]
Biospecimen Retention: Samples With DNA
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): NCT02100761
|Contact: Shifang Ding, Ph.D.||18560081003 ext +firstname.lastname@example.org|
|Qilu Hospital||Not yet recruiting|
|Jinan, Shandong, China, 250012|
|Contact: Shifang Ding, Ph.D. 18560081003 ext +86 email@example.com|
|Principal Investigator: Shifang Ding, Ph.D.|
|Study Chair:||Shifang Ding, Ph.D.||Qilu Hospital of Shandong University|