Clopidogrel Preventive Effect Based on CYP2C19 Genotype in Ischemic Stroke

Completed

• 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".

Study Timeline

• Study First Submitted: 2019-08-25
• Study First Submitted QC: 2019-08-27
• Study First Posted: 2019-08-28
• Study Start: 2019-09-20
• Primary Completion: 2023-01-11
• Study Completion: 2023-07-07
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-22
• Last Update Posted: 2023-09-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 2927

Inclusion Criteria

1. Ischemic stroke confirmed by brain CT or MRI
2. Patient who received clopidogrel within 72 hours after onset of ischemic stroke
3. Adults over 19 years
4. Patients who agreed to participate in this study within 7 days after ischemic stroke
5. Patients who underwent Cytochrome P450 2C19 genotype test.

Exclusion Criteria

1. Patients who currently take anticoagulation or is expected to take anticoagulation with 6 months from the screening date
2. Patients who need other antiplatelet drugs except aspirin and clopidogrel
3. Patients who were taking clopidogrel prior to ischemic stroke
4. Patients scheduled for coronary artery stenting, coronary artery bypass surgery, carotid endarterectomy, carotid and cerebral artery stenting
5. Patients with severe comorbidities or active cancer with an estimated life expectancy of less than two years
6. Patients who participated in other drug clinical trials within the past 30 days
7. Patients with high risk source of potential cardiac source of embolism in TOAST classification
8. 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)

Yongin Severance Hospital; 🇰🇷 Yongin-si, Gyeonggi-do, Korea, Republic of

Department of Neurology Korea University Ansan Hospital; 🇰🇷 Ansan, Korea, Republic of

Department of Neurology Hallym University Sacred Heart Hospital; 🇰🇷 Anyang, Korea, Republic of

Department of Neurology Inje University Busan Paik Hospital; 🇰🇷 Busan, Korea, Republic of

Department of Neurology Dong-A University Hospital; 🇰🇷 Busan, 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 Hallym University Chuncheon Sacred Heart Hospital; 🇰🇷 Chuncheon, Korea, Republic of

Department of Neurology Kangwon National University Hospital; 🇰🇷 Chuncheon, Korea, Republic of

Department of Neurology Keimyung University Dongsan Hospital; 🇰🇷 Daegu, Korea, Republic of

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