- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04072705
Clopidogrel Preventive Effect Based on CYP2C19 Genotype in Ischemic Stroke
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
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Ansan, Korea, Republic of, 15355
- Department of Neurology Korea University Ansan Hospital
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Anyang, Korea, Republic of, 14068
- Department of Neurology Hallym University Sacred Heart Hospital
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Busan, Korea, Republic of, 47392
- Department of Neurology Inje University Busan Paik Hospital
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Busan, Korea, Republic of, 49201
- Department of Neurology Dong-A University Hospital
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Busan, Korea, Republic of, 49267
- Department of Neurology Kosin University Gospel Hospital
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Changwon, Korea, Republic of, 51394
- Department of Neurology Changwon Fatima Hospital
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Chuncheon, Korea, Republic of, 24253
- Department of Neurology Hallym University Chuncheon Sacred Heart Hospital
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Chuncheon, Korea, Republic of, 24289
- Department of Neurology Kangwon National University Hospital
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Daegu, Korea, Republic of, 41931
- Department of Neurology Keimyung University Dongsan Hospital
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Daegu, Korea, Republic of, 41944
- Department of Neurology Kyungpook National University Hospital
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Daejeon, Korea, Republic of, 35233
- Department of Neurology Daejeon Eulji Medical Center Eulji University
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Gimpo-si, Korea, Republic of, 10099
- Department of Neurology Gimpo Woori Hospital
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Goyang, Korea, Republic of, 10444
- Department of Neurology National Health Insurance Service Ilsan Hospital
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Goyang, Korea, Republic of, 10475
- Department of Neurology Myongji Hospital
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Gwangju, Korea, Republic of, 61453
- Department of Neurology Chosun University Hospital
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Gwangju, Korea, Republic of, 61469
- Department of Neurology Chonnam National University Hospital
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Hwaseong-si, Korea, Republic of, 18450
- Department of Neurology Hallym University Dongtan Sacred Heart Hospital
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Iksan, Korea, Republic of, 54538
- Department of Neurology Wonkwang University Hospital
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Incheon, Korea, Republic of, 21565
- Department of Neurology Gachon University Gil Medical Center
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Incheon, Korea, Republic of, 22332
- Department of Neurology Inha University Hospital
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Incheon, Korea, Republic of, 22711
- Department of Neurology Catholic Kwandong University International St.Mary's Hospital
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Seongnam, Korea, Republic of, 13620
- Department of Neurology Seoul National University Bundang Hospital
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Seoul, Korea, Republic of, 01757
- Department of Neurology Inje University Sanggye Paik Hospital
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Seoul, Korea, Republic of, 02053
- Department of Neurology Seoul Medical Center
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Seoul, Korea, Republic of, 02447
- Department of Neurology KyungHee University Hospital
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Seoul, Korea, Republic of, 02841
- Department of Neurology Korea University Anam Hospital
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Seoul, Korea, Republic of, 03080
- Department of Neurology Seoul National University Hospital
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Seoul, Korea, Republic of, 03722
- Department of Neurology Severance Hospital, Yonsei University College of Medicine
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Seoul, Korea, Republic of, 04564
- Department of Neurology National Medical Center
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Seoul, Korea, Republic of, 04763
- Department of Neurology Hanyang University Seoul Hospital
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Seoul, Korea, Republic of, 05278
- Department of Neurology KyungHee University Hospital at Gangdong
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Seoul, Korea, Republic of, 05355
- Department of Neurology Kangdong Sacred Heart Hospital
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Seoul, Korea, Republic of, 06273
- Department of Neurology, Gangnam Severance Hospital, Yonsei Univ. College of Medicine
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Seoul, Korea, Republic of, 06973
- Department of Neurology Chung-Ang University Hospital
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Seoul, Korea, Republic of, 07804
- Department of Neurology Ewha Womans University Seoul Hospital
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Seoul, Korea, Republic of, 08308
- Department of Neurology Korea University Guro Hospital
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Gyeonggi-do
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Yongin-si, Gyeonggi-do, Korea, Republic of, 16995
- Yongin Severance Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
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
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
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.
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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.
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2. Extensive metabolizer group
Extensive metabolizer group: acute ischemic stroke patients with Extensive metabolizer genotype of cytochrome P450 2C19 for clopidogrel.
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
composite cardiovascular events
Time Frame: up to 6 months
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Occurrence of composite cardiovascular events (recurrent stroke, myocardial infarction, cardiovascular death)
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up to 6 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
cardiovascular events
Time Frame: up to 6 months
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Occurrence of ischemic stroke
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up to 6 months
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cardiovascular events
Time Frame: up to 6 months
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Occurrence of transient ischemic attack
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up to 6 months
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cardiovascular events
Time Frame: up to 6 months
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Revascularization of cerebral, coronary, peripheral artery or aorta
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up to 6 months
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cardiovascular events
Time Frame: up to 6 months
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Occurrence of myocardial infarction
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up to 6 months
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early neurological worsening
Time Frame: up to 7 days
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increased National Institutes of Health Stroke Scale within 7 day after admission)
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up to 7 days
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Prognosis
Time Frame: 3 months
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ratio of modified Rankin scale (0 - 2) at 3 months
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3 months
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of major adverse events
Time Frame: Tile frame: participants will be followed at 0, 1, 3, 6 months
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Occurrence of major bleeding (fatal bleeding, symptomatic cerebral hemorrhage, ocular hemorrhage, bleeding which needs absolute bed rest or hospitalization or transfusion (more than 2 pack of whole blood or RBC). Occurrence of all-causes mortality |
Tile frame: participants will be followed at 0, 1, 3, 6 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: KyungYul Lee, Gangnam Severance Hospital
Publications and helpful links
General Publications
- Nguyen TA, Diodati JG, Pharand C. Resistance to clopidogrel: a review of the evidence. J Am Coll Cardiol. 2005 Apr 19;45(8):1157-64. doi: 10.1016/j.jacc.2005.01.034.
- Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, Walker JR, Antman EM, Macias W, Braunwald E, Sabatine MS. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009 Jan 22;360(4):354-62. doi: 10.1056/NEJMoa0809171. Epub 2008 Dec 22.
- Simon T, Verstuyft C, Mary-Krause M, Quteineh L, Drouet E, Meneveau N, Steg PG, Ferrieres J, Danchin N, Becquemont L; French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) Investigators. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med. 2009 Jan 22;360(4):363-75. doi: 10.1056/NEJMoa0808227. Epub 2008 Dec 22.
- Shuldiner AR, O'Connell JR, Bliden KP, Gandhi A, Ryan K, Horenstein RB, Damcott CM, Pakyz R, Tantry US, Gibson Q, Pollin TI, Post W, Parsa A, Mitchell BD, Faraday N, Herzog W, Gurbel PA. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA. 2009 Aug 26;302(8):849-57. doi: 10.1001/jama.2009.1232.
- Mitsios JV, Papathanasiou AI, Rodis FI, Elisaf M, Goudevenos JA, Tselepis AD. Atorvastatin does not affect the antiplatelet potency of clopidogrel when it is administered concomitantly for 5 weeks in patients with acute coronary syndromes. Circulation. 2004 Mar 23;109(11):1335-8. doi: 10.1161/01.CIR.0000124581.18191.15. Epub 2004 Mar 15.
- Lau WC, Waskell LA, Watkins PB, Neer CJ, Horowitz K, Hopp AS, Tait AR, Carville DG, Guyer KE, Bates ER. Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation: a new drug-drug interaction. Circulation. 2003 Jan 7;107(1):32-7. doi: 10.1161/01.cir.0000047060.60595.cc.
- Collet JP, Hulot JS, Pena A, Villard E, Esteve JB, Silvain J, Payot L, Brugier D, Cayla G, Beygui F, Bensimon G, Funck-Brentano C, Montalescot G. Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study. Lancet. 2009 Jan 24;373(9660):309-17. doi: 10.1016/S0140-6736(08)61845-0. Epub 2008 Dec 26.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 3-2019-0195
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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