Clopidogrel Preventive Effect Based on CYP2C19 Genotype in Ischemic Stroke

NCT04072705 | Completed DMC FDA Drug

• 1 other identifier: 3-2019-0195
• Study Type: observational
• Target: 2,927
• Locations: 1 country
• Sites: 37

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".

Conditions

Acute Ischemic Stroke

Keywords

Pharmacogenetics; Cytochrome P450 2C19; Clopidogrel; Stroke

Outcome Measures

Primary Outcomes (1)

• composite cardiovascular events

  Occurrence of composite cardiovascular events (recurrent stroke, myocardial infarction, cardiovascular death)

  up to 6 months

Secondary Outcomes (6)

• cardiovascular events

  up to 6 months

• cardiovascular events

  up to 6 months

• cardiovascular events

  up to 6 months

• cardiovascular events

  up to 6 months

• early neurological worsening

  up to 7 days

Other Outcomes (1)

• Incidence of major adverse events

  Tile frame: participants will be followed at 0, 1, 3, 6 months

Study Arms (2)

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.

Drug: 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.

Drug: General principles of care and judgement of researcher

Interventions

General principles of care and judgement of researcher 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.

1. Poor and intermediate metabolizer group; 2. Extensive metabolizer group

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with acute ischemic stroke who received clopidogrel 75 mg to 300 mg (in the case of loading dose) within 24 hours of symptom onset and who underwent Cytochrome P450 2C19 genotyping test

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Gangnam Severance Hospital: lead
• SAMJIN PHARM: collaborator

Study Sites (37)

Yongin Severance Hospital

Yongin-si, Gyeonggi-do, 16995, South Korea

Location

Department of Neurology Korea University Ansan Hospital

Ansan, 15355, South Korea

Location

Department of Neurology Hallym University Sacred Heart Hospital

Anyang, 14068, South Korea

Location

Department of Neurology Inje University Busan Paik Hospital

Busan, 47392, South Korea

Location

Department of Neurology Dong-A University Hospital

Busan, 49201, South Korea

Location

Department of Neurology Kosin University Gospel Hospital

Busan, 49267, South Korea

Location

Department of Neurology Changwon Fatima Hospital

Changwon, 51394, South Korea

Location

Department of Neurology Hallym University Chuncheon Sacred Heart Hospital

Chuncheon, 24253, South Korea

Location

Department of Neurology Kangwon National University Hospital

Chuncheon, 24289, South Korea

Location

Department of Neurology Keimyung University Dongsan Hospital

Daegu, 41931, South Korea

Location

Department of Neurology Kyungpook National University Hospital

Daegu, 41944, South Korea

Location

Department of Neurology Daejeon Eulji Medical Center Eulji University

Daejeon, 35233, South Korea

Location

Department of Neurology Gimpo Woori Hospital

Gimpo-si, 10099, South Korea

Location

Department of Neurology National Health Insurance Service Ilsan Hospital

Goyang, 10444, South Korea

Location

Department of Neurology Myongji Hospital

Goyang, 10475, South Korea

Location

Department of Neurology Chosun University Hospital

Gwangju, 61453, South Korea

Location

Department of Neurology Chonnam National University Hospital

Gwangju, 61469, South Korea

Location

Department of Neurology Hallym University Dongtan Sacred Heart Hospital

Hwaseong-si, 18450, South Korea

Location

Department of Neurology Wonkwang University Hospital

Iksan, 54538, South Korea

Location

Department of Neurology Gachon University Gil Medical Center

Incheon, 21565, South Korea

Location

Department of Neurology Inha University Hospital

Incheon, 22332, South Korea

Location

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

Incheon, 22711, South Korea

Location

Department of Neurology Seoul National University Bundang Hospital

Seongnam, 13620, South Korea

Location

Department of Neurology Inje University Sanggye Paik Hospital

Seoul, 01757, South Korea

Location

Department of Neurology Seoul Medical Center

Seoul, 02053, South Korea

Location

Department of Neurology KyungHee University Hospital

Seoul, 02447, South Korea

Location

Department of Neurology Korea University Anam Hospital

Seoul, 02841, South Korea

Location

Department of Neurology Seoul National University Hospital

Seoul, 03080, South Korea

Location

Department of Neurology Severance Hospital, Yonsei University College of Medicine

Seoul, 03722, South Korea

Location

Department of Neurology National Medical Center

Seoul, 04564, South Korea

Location

Department of Neurology Hanyang University Seoul Hospital

Seoul, 04763, South Korea

Location

Department of Neurology KyungHee University Hospital at Gangdong

Seoul, 05278, South Korea

Location

Department of Neurology Kangdong Sacred Heart Hospital

Seoul, 05355, South Korea

Location

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

Seoul, 06273, South Korea

Location

Department of Neurology Chung-Ang University Hospital

Seoul, 06973, South Korea

Location

Department of Neurology Ewha Womans University Seoul Hospital

Seoul, 07804, South Korea

Location

Department of Neurology Korea University Guro Hospital

Seoul, 08308, South Korea

Location

Related Publications (14)

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• 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.

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• 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.

  PMID: 19106084 BACKGROUND

• 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.

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• 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.

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• 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.

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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.

  PMID: 27806998 BACKGROUND

• 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.

  PMID: 27348249 BACKGROUND

• 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.

  PMID: 40184070 DERIVED

• 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.

  PMID: 32759249 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Cytochrome P450 2C19 genotype

MeSH Terms

Conditions

Ischemic Stroke; Stroke

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• KyungYul Lee

  Gangnam Severance Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: KyungYul Lee, Professor

Study Record Dates

• First Submitted: August 25, 2019
• First Posted: August 28, 2019
• Study Start: September 20, 2019
• Primary Completion: January 11, 2023
• Study Completion: July 7, 2023
• Last Updated: September 25, 2023

Record last verified: 2023-09

Locations

KR (37)