Clopidogrel Preventive Effect Based on CYP2C19 Genotype in Ischemic Stroke
- Conditions
- Acute Ischemic Stroke
- Interventions
- Drug: General principles of care and judgement of researcher
- Registration Number
- NCT04072705
- Lead Sponsor
- Gangnam Severance Hospital
- Brief Summary
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
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".
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 2927
- 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.
- 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
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description 1. Poor and intermediate metabolizer group General principles of care and judgement of researcher Poor and intermediate metabolizer group: acute ischemic stroke patients with poor and intermediate metabolizer genotype of cytochrome P450 2C19 for clopidogrel. 2. Extensive metabolizer group General principles of care and judgement of researcher Extensive metabolizer group: acute ischemic stroke patients with Extensive metabolizer genotype of cytochrome P450 2C19 for clopidogrel.
- Primary Outcome Measures
Name Time Method composite cardiovascular events up to 6 months Occurrence of composite cardiovascular events (recurrent stroke, myocardial infarction, cardiovascular death)
- Secondary Outcome Measures
Name Time Method cardiovascular events up to 6 months Occurrence of myocardial infarction
Prognosis 3 months ratio of modified Rankin scale (0 - 2) at 3 months
early neurological worsening up to 7 days increased National Institutes of Health Stroke Scale within 7 day after admission)
Trial Locations
- Locations (37)
Department of Neurology Dong-A University Hospital
🇰🇷Busan, Korea, Republic of
Department of Neurology Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Department of Neurology Severance Hospital, Yonsei University College of Medicine
🇰🇷Seoul, Korea, Republic of
Department of Neurology Kangdong Sacred Heart Hospital
🇰🇷Seoul, Korea, Republic of
Department of Neurology Kosin University Gospel Hospital
🇰🇷Busan, Korea, Republic of
Department of Neurology Changwon Fatima Hospital
🇰🇷Changwon, Korea, Republic of
Department of Neurology Kangwon National University Hospital
🇰🇷Chuncheon, Korea, Republic of
Department of Neurology Chosun University Hospital
🇰🇷Gwangju, Korea, Republic of
Department of Neurology, Gangnam Severance Hospital, Yonsei Univ. College of Medicine
🇰🇷Seoul, Korea, Republic of
Department of Neurology Chung-Ang University Hospital
🇰🇷Seoul, Korea, Republic of
Department of Neurology Ewha Womans University Seoul Hospital
🇰🇷Seoul, Korea, Republic of
Department of Neurology Inje University Busan Paik Hospital
🇰🇷Busan, Korea, Republic of
Yongin Severance Hospital
🇰🇷Yongin-si, Gyeonggi-do, Korea, Republic of
Department of Neurology Hallym University Sacred Heart Hospital
🇰🇷Anyang, Korea, Republic of
Department of Neurology Hallym University Chuncheon Sacred Heart Hospital
🇰🇷Chuncheon, Korea, Republic of
Department of Neurology Keimyung University Dongsan Hospital
🇰🇷Daegu, Korea, Republic of
Department of Neurology Gimpo Woori Hospital
🇰🇷Gimpo-si, Korea, Republic of
Department of Neurology Myongji Hospital
🇰🇷Goyang, Korea, Republic of
Department of Neurology Hallym University Dongtan Sacred Heart Hospital
🇰🇷Hwaseong-si, Korea, Republic of
Department of Neurology Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Department of Neurology KyungHee University Hospital at Gangdong
🇰🇷Seoul, Korea, Republic of
Department of Neurology Kyungpook National University Hospital
🇰🇷Daegu, Korea, Republic of
Department of Neurology National Health Insurance Service Ilsan Hospital
🇰🇷Goyang, Korea, Republic of
Department of Neurology Wonkwang University Hospital
🇰🇷Iksan, Korea, Republic of
Department of Neurology Catholic Kwandong University International St.Mary's Hospital
🇰🇷Incheon, Korea, Republic of
Department of Neurology Seoul National University Bundang Hospital
🇰🇷Seongnam, Korea, Republic of
Department of Neurology Korea University Ansan Hospital
🇰🇷Ansan, Korea, Republic of
Department of Neurology Daejeon Eulji Medical Center Eulji University
🇰🇷Daejeon, Korea, Republic of
Department of Neurology Chonnam National University Hospital
🇰🇷Gwangju, Korea, Republic of
Department of Neurology Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
Department of Neurology Inha University Hospital
🇰🇷Incheon, Korea, Republic of
Department of Neurology Inje University Sanggye Paik Hospital
🇰🇷Seoul, Korea, Republic of
Department of Neurology Seoul Medical Center
🇰🇷Seoul, Korea, Republic of
Department of Neurology KyungHee University Hospital
🇰🇷Seoul, Korea, Republic of
Department of Neurology National Medical Center
🇰🇷Seoul, Korea, Republic of
Department of Neurology Hanyang University Seoul Hospital
🇰🇷Seoul, Korea, Republic of
Department of Neurology Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of