Platelet Aggregation InhibitorsNCT02711410
The Influence of CYP2C19 Polymorphism and Clinical Outcomes in Stroke Patients
An observational study of Platelet Aggregation Inhibitors, run by National Cerebral and Cardiovascular Center, Japan.
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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Platelet Aggregation Inhibitors
- What is being tested?
- Clopidogrel
- How many people
- 518 participants
- Where
- No sites listed yet
- Study dates
- Oct 2009to Oct 2015
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients were recruited at each institution between October 2009 and March 2012. The investigators enrolled males and females aged 20 years or older who had experienced cerebral infarction or transient ischemic attack (TIA) (except for cardiogenic embolism) in the prior 3 years but not in the last one month, who received long-term clopidogrel therapy (75 mg once a day) for the secondary prevention (for at least one month), and who were willing and able to give written informed consent.
Who may be able to join
- 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.
Who cannot join
- 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
About this study
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
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.
Read more
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
- Being tested
- Clopidogrel
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClopidogrelDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Two Years
Secondary outcomes (1)
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.
Measured: two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2016 (estimated)
- Study startOct 2009
- Primary completionApr 2014
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Platelet Aggregation InhibitorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 518 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cerebral and Cardiovascular Center, Japan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tomotaka Tanaka, National Cerebral and Cardiovascular Center, Japan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02711410
- Sponsor's protocol ID
- NationalCardioCenterCognac
- Status last verified
- Mar 2016
- First submitted
- 9 Mar 2016
- Last updated
- 18 Mar 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02711410
- Acronym / sponsor ID
- NationalCardioCenterCognac
- Conditions
- Platelet Aggregation Inhibitors
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 518 participants (actual)
- Lead sponsor
- National Cerebral and Cardiovascular Center, JapanUniversity, hospital or other
- Study start
- Oct 2009
- Primary completion
- Apr 2014 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 17 Mar 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients were recruited at each institution between October 2009 and March 2012. The investigators enrolled males and females aged 20 years or older who had experienced cerebral infarction or transient ischemic attack (TIA) (except for cardiogenic embolism) in the prior 3 years but not in the last one month, who received long-term clopidogrel therapy (75 mg once a day) for the secondary prevention (for at least one month), and who were willing and able to give written informed consent.
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Clopidogrel | Drug | – |
Primary outcome
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.
Time frame: Two Years
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.
1 secondary outcome
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).
Time frame: two years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2016.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
An observational study of Platelet Aggregation Inhibitors, run by National Cerebral and Cardiovascular Center, Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: Two Years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2016.