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Trial record 19 of 58 for:    "Aspergillosis" | "Cytochrome P-450 CYP3A Inhibitors"

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
Sponsor:
Collaborators:
Shandong Provincial Hospital
Qianfoshan Hospital
Shandong thorax hospital
Jinan Military General Hospital
Jinan Central Hospital
Information provided by (Responsible Party):
dingshifang, Qilu Hospital of Shandong University

Brief Summary:
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.

Condition or disease Intervention/treatment
Invasive Pulmonary Aspergillosis Drug: Voriconazole

Detailed Description:

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)


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Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Case-Only
Time Perspective: Prospective
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Aspergillosis

Group/Cohort Intervention/treatment
invasive pulmonary aspergillosis
Patients with invasive pulmonary aspergillosis and will be treated with voriconazole according to their physician decision in five hospital, Jinan, China
Drug: Voriconazole
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).
Other Names:
  • Voriconazole Intravenous Solution 200 mg
  • Voriconazole Tablet 50 mg / Voriconazole Tablet 200 mg




Primary Outcome Measures :
  1. voriconazole trough level [ Time Frame: one year ]

Secondary Outcome Measures :
  1. Overall mortality [ Time Frame: one year ]

Biospecimen Retention:   Samples With DNA
The susceptibility test of aspergillosis strains to voriconazole, serum galactomannan (GM) test, voriconazole trough levels and genotyping of CYP2C19 will be measured.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients with invasive pulmonary aspergillosis and will be treated with voriconazole according to their physician decision
Criteria

Inclusion Criteria:

  • Proven, probable, or possible invasive pulmonary aspergillosis (IPA)
  • Acute IPA defined as duration of clinical syndrome of <30 days.
  • Treatment with voriconazole
  • At least 18 years and older
  • Weight >40 kg and ≤120 kg
  • Given the informed consent

Exclusion Criteria:

  • Patients allergic to azole(s)
  • Patients who heve been prescribed voriconazole before
  • Positive urine pregnancy test (if female)
  • Patients with aspergilloma or chronic aspergillosis ( >1 month duration )
  • Anticipated survival of less than 5 days or Karnofsky score <=20

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): NCT02100761


Contacts
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Contact: Shifang Ding, Ph.D. 18560081003 ext +86 dingshifang@sdu.edu.cn

Locations
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China, Shandong
Qilu Hospital Not yet recruiting
Jinan, Shandong, China, 250012
Contact: Shifang Ding, Ph.D.    18560081003 ext +86    dingshifang@sdu.edu.cn   
Principal Investigator: Shifang Ding, Ph.D.         
Sponsors and Collaborators
dingshifang
Shandong Provincial Hospital
Qianfoshan Hospital
Shandong thorax hospital
Jinan Military General Hospital
Jinan Central Hospital
Investigators
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Study Chair: Shifang Ding, Ph.D. Qilu Hospital of Shandong University

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Responsible Party: dingshifang, Professor, Qilu Hospital of Shandong University
ClinicalTrials.gov Identifier: NCT02100761     History of Changes
Other Study ID Numbers: KYLL-2014(KS)-085
First Posted: April 1, 2014    Key Record Dates
Last Update Posted: April 1, 2014
Last Verified: March 2014
Keywords provided by dingshifang, Qilu Hospital of Shandong University:
Voriconazole
Invasive pulmonary aspergillosis
Therapeutic drug monitoring
CYP genetic polymorphism
Efficacy
Safety
Additional relevant MeSH terms:
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Aspergillosis
Pulmonary Aspergillosis
Invasive Pulmonary Aspergillosis
Cytochrome P-450 CYP3A Inhibitors
Mycoses
Lung Diseases, Fungal
Lung Diseases
Respiratory Tract Diseases
Invasive Fungal Infections
Voriconazole
Antifungal Agents
Anti-Infective 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