The Influence of CYP2C19 Polymorphism and Clinical Outcomes in Stroke Patients

Platelet Aggregation Inhibitors Clinical Trial

Official title:

The Influence of CYP2C19 Polymorphism on Antiplatelet Effects and Clinical Outcomes in Non-acute Stroke Patients Treated With Clopidogrel: The Contribution of Genetic Analysis to the Efficacy of Clopidogrel (Cognac) Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02711410
• Other study ID #: NationalCardioCenterCognac
• Status: Completed
• Phase: N/A
• First received: March 9, 2016
• Last updated: March 17, 2016
• Start date: October 2009
• Est. completion date: October 2015

Study information

• Verified date: March 2016
• Source: National Cerebral and Cardiovascular Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Institutional Review Board
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 518
• Est. completion date: October 2015
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Platelet Aggregation Inhibitors

Intervention

Drug:
• Clopidogrel

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
National Cerebral and Cardiovascular Center

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary outcome of the study was recurrent cardiovascular event (CVEs), including ischemic stroke, transient ischemic attack (TIA), acute myocardial infarction, urgent revascularization, other thromboembolic disease, and cardiovascular death.	Ischemic stroke was defined as a new neurologic deficit of cardiovascular origin lasting at least > 24 hours based on radiological evidence of stroke. TIA was defined as a transient episode of neurologic dysfunction caused by focal brain ischemia and improving within 24 hours. Urgent revascularization was defined as emergent revascularization for unexpected hospitalization. Acute myocardial infarction was defined as myocardial cell necrosis in the setting of ischemic symptoms and electrocardiogram changes (ST segment elevation or depression, development of Q waves) and/or rising specific cardiac biomarkers. Cardiovascular death was defined as death due to stroke, myocardial infarction or documented sudden cardiac death.	Two Years	Yes
Secondary	Secondary outcome was major bleeding (intracranial haemorrhage, documented retroperitoneal bleed, and any red blood cell transfusion rates or proportion with bleeding associated with a ?2g/dl hemoglobin drop).	Intracranial haemorrhage retroperitoneal bleed were defined on radiological evidence. Proportion with bleeding associated with a ?2g/dl hemoglobin drop was assessed by Blood laboratory test.	two years	Yes