Clopidogrel Preventive Effect Based on CYP2C19 Genotype in Ischemic Stroke

NCT ID: NCT04072705

Last Updated: 2023-09-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

2927 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-09-20

Study Completion Date

2023-07-07

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".

Conditions

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Acute Ischemic Stroke

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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1. Poor and intermediate metabolizer group

Poor and intermediate metabolizer group: acute ischemic stroke patients with poor and intermediate metabolizer genotype of cytochrome P450 2C19 for clopidogrel.

General principles of care and judgement of researcher

Intervention Type DRUG

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.

2. Extensive metabolizer group

Extensive metabolizer group: acute ischemic stroke patients with Extensive metabolizer genotype of cytochrome P450 2C19 for clopidogrel.

General principles of care and judgement of researcher

Intervention Type DRUG

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.

Interventions

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General principles of care and judgement of researcher

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.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

19 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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SAMJIN PHARM

UNKNOWN

Sponsor Role collaborator

Gangnam Severance Hospital

OTHER

Sponsor Role lead

Responsible Party

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Kyung-Yul Lee

KyungYul Lee, Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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KyungYul Lee

Role: PRINCIPAL_INVESTIGATOR

Gangnam Severance Hospital

Locations

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Yongin Severance Hospital

Yongin-si, Gyeonggi-do, South Korea

Site Status

Department of Neurology Korea University Ansan Hospital

Ansan, , South Korea

Site Status

Department of Neurology Hallym University Sacred Heart Hospital

Anyang, , South Korea

Site Status

Department of Neurology Inje University Busan Paik Hospital

Busan, , South Korea

Site Status

Department of Neurology Dong-A University Hospital

Busan, , South Korea

Site Status

Department of Neurology Kosin University Gospel Hospital

Busan, , South Korea

Site Status

Department of Neurology Changwon Fatima Hospital

Changwon, , South Korea

Site Status

Department of Neurology Hallym University Chuncheon Sacred Heart Hospital

Chuncheon, , South Korea

Site Status

Department of Neurology Kangwon National University Hospital

Chuncheon, , South Korea

Site Status

Department of Neurology Keimyung University Dongsan Hospital

Daegu, , South Korea

Site Status

Department of Neurology Kyungpook National University Hospital

Daegu, , South Korea

Site Status

Department of Neurology Daejeon Eulji Medical Center Eulji University

Daejeon, , South Korea

Site Status

Department of Neurology Gimpo Woori Hospital

Gimpo-si, , South Korea

Site Status

Department of Neurology National Health Insurance Service Ilsan Hospital

Goyang, , South Korea

Site Status

Department of Neurology Myongji Hospital

Goyang, , South Korea

Site Status

Department of Neurology Chosun University Hospital

Gwangju, , South Korea

Site Status

Department of Neurology Chonnam National University Hospital

Gwangju, , South Korea

Site Status

Department of Neurology Hallym University Dongtan Sacred Heart Hospital

Hwaseong-si, , South Korea

Site Status

Department of Neurology Wonkwang University Hospital

Iksan, , South Korea

Site Status

Department of Neurology Gachon University Gil Medical Center

Incheon, , South Korea

Site Status

Department of Neurology Inha University Hospital

Incheon, , South Korea

Site Status

Department of Neurology Catholic Kwandong University International St.Mary's Hospital

Incheon, , South Korea

Site Status

Department of Neurology Seoul National University Bundang Hospital

Seongnam, , South Korea

Site Status

Department of Neurology Inje University Sanggye Paik Hospital

Seoul, , South Korea

Site Status

Department of Neurology Seoul Medical Center

Seoul, , South Korea

Site Status

Department of Neurology KyungHee University Hospital

Seoul, , South Korea

Site Status

Department of Neurology Korea University Anam Hospital

Seoul, , South Korea

Site Status

Department of Neurology Seoul National University Hospital

Seoul, , South Korea

Site Status

Department of Neurology Severance Hospital, Yonsei University College of Medicine

Seoul, , South Korea

Site Status

Department of Neurology National Medical Center

Seoul, , South Korea

Site Status

Department of Neurology Hanyang University Seoul Hospital

Seoul, , South Korea

Site Status

Department of Neurology KyungHee University Hospital at Gangdong

Seoul, , South Korea

Site Status

Department of Neurology Kangdong Sacred Heart Hospital

Seoul, , South Korea

Site Status

Department of Neurology, Gangnam Severance Hospital, Yonsei Univ. College of Medicine

Seoul, , South Korea

Site Status

Department of Neurology Chung-Ang University Hospital

Seoul, , South Korea

Site Status

Department of Neurology Ewha Womans University Seoul Hospital

Seoul, , South Korea

Site Status

Department of Neurology Korea University Guro Hospital

Seoul, , South Korea

Site Status

Countries

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South Korea

References

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Pan Y, Chen W, Xu Y, Yi X, Han Y, Yang Q, Li X, Huang L, Johnston SC, Zhao X, Liu L, Zhang Q, Wang G, Wang Y, Wang Y. Genetic Polymorphisms and Clopidogrel Efficacy for Acute Ischemic Stroke or Transient Ischemic Attack: A Systematic Review and Meta-Analysis. Circulation. 2017 Jan 3;135(1):21-33. doi: 10.1161/CIRCULATIONAHA.116.024913. Epub 2016 Nov 2.

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Han SW, Kim YJ, Ahn SH, Seo WK, Yu S, Oh SH, Nam HS, Choi HY, Yoon SS, Kim SH, Lee JY, Lee JH, Hwang YH, Lee KO, Jung YH, Lee J, Sohn SI, Kim YN, Lee KA, Bushnell CD, Lee KY. Effects of Triflusal and Clopidogrel on the Secondary Prevention of Stroke Based on Cytochrome P450 2C19 Genotyping. J Stroke. 2017 Sep;19(3):356-364. doi: 10.5853/jos.2017.01249. Epub 2017 Sep 29.

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Lee SS, Lee SJ, Gwak J, Jung HJ, Thi-Le H, Song IS, Kim EY, Shin JG. Comparisons of CYP2C19 genetic polymorphisms between Korean and Vietnamese populations. Ther Drug Monit. 2007 Aug;29(4):455-9. doi: 10.1097/FTD.0b013e31811f383c.

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Wang Y, Zhao X, Lin J, Li H, Johnston SC, Lin Y, Pan Y, Liu L, Wang D, Wang C, Meng X, Xu J, Wang Y; CHANCE investigators. Association Between CYP2C19 Loss-of-Function Allele Status and Efficacy of Clopidogrel for Risk Reduction Among Patients With Minor Stroke or Transient Ischemic Attack. JAMA. 2016 Jul 5;316(1):70-8. doi: 10.1001/jama.2016.8662.

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CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet. 1996 Nov 16;348(9038):1329-39. doi: 10.1016/s0140-6736(96)09457-3.

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Jung YH, Song TJ, Kim J, Park HK, Han SW, Kim YD, Park JH, Cha JK, Park HY, Sohn SI, Yu S, Lee JH, Shin DH, Kim EG, Lee HS, Lee KY; PLATELET Trial Investigators. Cytochrome P450 2C19 Genotypes and Clopidogrel in Patients With Ischemic Stroke: A Nonrandomized Clinical Trial. JAMA Netw Open. 2025 Apr 1;8(4):e250398. doi: 10.1001/jamanetworkopen.2025.0398.

Reference Type DERIVED
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Song TJ, Kim J, Han SW, Kim YD, Lee JY, Ahn SH, Lee HS, Jung YH, Lee KY. Clopidogrel preventive effect based on cytochrome P450 2C19 genotype in ischaemic stroke: protocol for multicentre observational study. BMJ Open. 2020 Aug 5;10(8):e038031. doi: 10.1136/bmjopen-2020-038031.

Reference Type DERIVED
PMID: 32759249 (View on PubMed)

Other Identifiers

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3-2019-0195

Identifier Type: -

Identifier Source: org_study_id

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