The Influence of CYP2C19 Polymorphism and Clinical Outcomes in Stroke Patients

NCT ID: NCT02711410

Last Updated: 2016-03-18

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 518 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2015-10-31

Brief Summary

Background:

Clopidogrel, an antiplatelet prodrug, is widely used for prevention of the recurrent cardiovascular events. CYP2C19 is one of the crucial enzymes for the activation of clopidogrel. Recent studies, mostly done in cardiovascular patients, showed association of the CYP2C19 genotypes with recurrent cardiovascular events. However, prospective data on the impact of the genetic variants in stroke patients are limited.

Methods:

Five hundred and eighteen Japanese non-acute stroke patients treated with clopidogrel were registered at 14 institutions. Three CYP2C19 variants (CYP2C19*2, *3, *17) were genotyped and the patients were classified into three clopidogrel metabolizer groups inferred from the CYP2C19 genotypes: extensive (EM: *1/*1), intermediate (IM: *1/*2 or *1/*3), and poor (PM: *2/*2, *2/*3, or *3/*3). The CYP2C19*17 carriers were excluded from the analysis. The antiplatelet effects of clopidogrel were assessed by Adenosine diphosphate (ADP) -induced platelet aggregation and vasodilator-stimulated phosphoprotein (VASP) phosphorylation, expressed as VASP index. The endpoint was the composite incidence of stroke, transient ischemic attack, myocardial infarction, revascularization, other thromboembolic disease, or cardiovascular death during 2 years of follow-up.

Conditions

Platelet Aggregation Inhibitors

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

Clopidogrel

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients who had received long-term clopidogrel therapy (once a day for at least one month) with a minimum one-month interval between enrollment and the last cerebral ischemic or TIA event.
• Males and females aged 20 years or older who were prescribed clopidogrel for the secondary prevention of cerebral infarction or transient ischemic attack and who were willing and able to give written informed consent.

Exclusion Criteria

• Malignancies
• Congenital bleeding tendency
• Atrial fibrillation
• Concomitant use of an oral anticoagulant agent
• a platelet count of < 100 x 109/L or > 450 x 109/L within 3 months of enrollment
• Modified rankin scale > 4

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cerebral and Cardiovascular Center, Japan

OTHER

Sponsor Role: lead

Responsible Party

Tomotaka Tanaka

Medical Researcher, Department of Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Other Identifiers

NationalCardioCenterCognac

Identifier Type: -

Identifier Source: org_study_id