Clopidogrel Preventive Effect Based on CYP2C19 Genotype in Ischemic Stroke

Study Overview
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Brief Summary
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The hypothesis of this study is that the poor metabolizer or intermediate metabolizer of the cytochrome P450 2C19 genotype in patients with acute ischemic stroke is associated with increased risk of composite cardiovascular events (recurrent stroke, myocardial infarction, cardiovascular death) compared to those who of extensive metabolizer of the cytochrome P450 2C19 genotype.

Detailed Description
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Clopidogrel, one of the antiplatelet agents used for secondary prevention in patients with ischemic stroke and coronary artery disease, has been shown to have a superior antiplatelet effect compared to aspirin, and is therefore being administered to many patients with stroke and coronary artery disease. Clopidogrel inhibits platelet-derived ADP receptor, P2Y12, in the liver to produce an anti-platelet effect. It has been suggested that clopidogrel resistance could be occurred from drug-drug interaction via the same pharmacological metabolic pathway. Previous studies reported that the genotypes of Cytochrome P450 2C19, which is involved in the metabolism of clopidogrel in the liver, lead to differences in drug response and recurrence rates of cardiovascular disease. The risk of recurrence of ischemic stroke was reported to be about 4 times higher in patients with a poor metabolizer or intermediate metabolizer genotype of the Cytochrome P450 2C19 genotype compared to the extensive metabolizer genotype. This genotypes of Cytochrome P450 2C19 were also different according to race. The researches about cytochrome P450 2C19 genotype and clopidogrel resistance have been conducted mainly in patients with coronary artery disease and are not known in stroke patients. Few studies have examined whether the resistance of clopidogrel according to the genotype of cytochrome P450 2C19 in stroke patients is related to the occurrence and/or recurrence of cardiovascular disease. The hypothesis of this study is that the poor metabolizer or intermediate metabolizer of the cytochrome P450 2C19 genotype in patients with acute ischemic stroke is associated with increased risk of cardiovascular disease and mortality compared to those who of extensive metabolizer of the cytochrome P450 2C19 genotype.

Official Title
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A Multicenter Prospective observationaL Study to evAluate the effecT of Clopidogrel on the prEvention of Major vascuLar Events According to the gEnotype of Cytochrome P450 2C19 in Ischemic Stroke paTients; PLATELET Study

Conditions
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Acute Ischemic Stroke

Intervention / Treatment
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* Drug: General principles of care and judgement of researcher


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ischemic stroke confirmed by brain CT or MRI Patient who received clopidogrel within 72 hours after onset of ischemic stroke Adults over 19 years Patients who agreed to participate in this study within 7 days after ischemic stroke Patients who underwent Cytochrome P450 2C19 genotype test. Exclusion Criteria: Patients who currently take anticoagulation or is expected to take anticoagulation with 6 months from the screening date Patients who need other antiplatelet drugs except aspirin and clopidogrel Patients who were taking clopidogrel prior to ischemic stroke Patients scheduled for coronary artery stenting, coronary artery bypass surgery, carotid endarterectomy, carotid and cerebral artery stenting Patients with severe comorbidities or active cancer with an estimated life expectancy of less than two years Patients who participated in other drug clinical trials within the past 30 days Patients with high risk source of potential cardiac source of embolism in TOAST classification Patients who are expected to unable to participate or continue the study

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1. Poor and intermediate metabolizer group<br>Poor and intermediate metabolizer group: acute ischemic stroke patients with poor and intermediate metabolizer genotype of cytochrome P450 2C19 for clopidogrel. | Drug: General principles of care and judgement of researcher<br>* Because our study will be performed by observational design, there will be no intervention for our study. Because it is a registry-based study, overall decision making for medications will be performed according to the general principles of care and judgement of researcher.<br>|
| 2. Extensive metabolizer group<br>Extensive metabolizer group: acute ischemic stroke patients with Extensive metabolizer genotype of cytochrome P450 2C19 for clopidogrel. | Drug: General principles of care and judgement of researcher<br>* Because our study will be performed by observational design, there will be no intervention for our study. Because it is a registry-based study, overall decision making for medications will be performed according to the general principles of care and judgement of researcher.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| composite cardiovascular events | Occurrence of composite cardiovascular events (recurrent stroke, myocardial infarction, cardiovascular death) | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cardiovascular events | Occurrence of ischemic stroke | up to 6 months | 
| cardiovascular events | Occurrence of transient ischemic attack | up to 6 months | 
| cardiovascular events | Revascularization of cerebral, coronary, peripheral artery or aorta | up to 6 months | 
| cardiovascular events | Occurrence of myocardial infarction | up to 6 months | 
| early neurological worsening | increased National Institutes of Health Stroke Scale within 7 day after admission) | up to 7 days | 
| Prognosis | ratio of modified Rankin scale (0 - 2) at 3 months | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacogenetics, Cytochrome P450 2C19, Clopidogrel, Stroke