Clopidogrel Pharmacogenetic Score System

NCT ID: NCT01990989

Last Updated: 2013-11-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

500 participants

Study Classification

OBSERVATIONAL

Study Start Date

2014-01-31

Study Completion Date

2015-01-31

Brief Summary

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The aim of the present study is to evaluate candidate variables,including Cytochrome P450 2C19(CYP2C19) genotypes, clinical and demographic variables,to establish a simple risk score that can be easily adopted by clinicians to identify patients who are at risk for HPR and composite cardiovascular outcomes in Chinese Han patients treated with dual antiplatelet therapy.

Detailed Description

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There is a large inter-individual variability of biological antiplatelet responsiveness in patients treated with clopidogrel. Our previous study suggested that in clopidogrel treated Chinese patients with acute coronary syndromes(ACS),carriers of at least one CYP2C19 loss-of-function allele could predict greater risk of high on-treatment platelet reactivity (HPR), with the impact mainly attributing to CYP2C19\*2. But as we know, CYP2C19\*2 could only explain a small proportion of the variability. Various clinical and demographic variables have been considered to influence response to antiplatelet therapy.

Study objectives:

The present study aims to evaluate candidate variables,including CYP2C19 gene polymorphisms, clinical and demographic variables,to establish a simple risk score to identify patients who are at risk for HPR and composite cardiovascular outcomes .

Study design:

Step 1: Population enrollment and medication This mono-center study will be conducted in General Hospital of Chinese People's Liberation Army. Consecutive patients more than 18 years old admitted for ACS will be recruited after giving informed consents. After admission, all enrolled patients will be treated with 100 mg aspirin and 75mg clopidogrel per day. A loading dose of 300 mg clopidogrel will be given to patients undergoing coronary angiography.

Step 2: Clinical and demographic data collection A detailed demographic and medical data will be extracted from medical charts and prescription records. For the development of the risk score system, we will chose variables that are available in routine clinical practice. Clinical candidate variables include smoking history, diabetes,hypertension, renal failure with a serum creatinine\>1.5mg/dL-1, hypercholesterolemia, left ventricular dysfunction, age, gender, acute coronary syndrome on admission and co-medication with statins, calcium channel inhibitor, and proton pump inhibitors.

Step 3 : Platelet function measurements and Genotyping After 5 days maintenance dose of clopidogrel administration, blood samples will be drawn for light transmittance aggregometry (LTA) testing, using an APACT-4 aggregometer (LABiTec, Germany). The magnitude of on-treatment platelet reactivity was quantified using LTA with 20µmol/L ADP(adenosine disphosphate) as the agonist. Aggregation was expressed as the maximal percentage change in light transmittance from baseline, with platelet-poor plasma as the reference.

Genomic DNA will be extracted from the peripheral blood leucocytes of each patient. The loss of function alleles, CYP2C19\*2 (rs4244285) and CYP2C19\*3 (rs4986893), will be genotyped by the polymerase chain reaction(PCR)-ligase detection reactions(LDR)sequencing method.

Step 4: Follow-up At one year, the incidence of composite cardiovascular outcomes will be assessed by review of the patients'charts on re-admission or by telephone interview. Telephone interviewers are blinded with respect to the results of platelet aggregation and genotypes.

Step 5: Statistical analysis and development of risk score Logistic regression and Cox proportional hazards survival regression will be used to develop the risk score system with the candidate variables including clinical and demographic variables, CYP2C19 genotypes, and platelet aggregation.

Conditions

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Acute Coronary Syndrome

Keywords

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clopidogrel pharmacogenomics CYP2C19 platelet aggregation score system ischemic cardiovascular outcomes hemorrhage complications

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Clopidogrel treated patients

A consecutive cohort with 500 cases treated with 75mg/day maintenance dose of clopidogrel.

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* Patients more than 18 years old
* Admitted for ACS to the Department of Geriatric Cardiology, General Hospital of Chinese People's Liberation Army
* The diagnosis of ACS according to the American Heart Association/American College of Cardiology (AHA/ACC) criteria, 2012

Exclusion Criteria

* Known contraindication to dual anti-platelet therapy
* History of chronic inflammatory disease
* Steroidal and non-steroidal anti-inflammatory drugs use
* Previous administration of antiplatelet drugs within 1 month before coronary artery angiography
* Illicit drug abuse
* Significant bleeding tendency
* Cerebrovascular events within 3months
* Major surgery within 4 weeks
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Chinese PLA General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Tong Yin

Research Associate of Institute of Geriatric Cardiology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Tong Yin, Dr.

Role: PRINCIPAL_INVESTIGATOR

Institute of Geriatric Cardiology, General Hospital of People's Liberation Army, Beijing China

Locations

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Institute of Geriatric Cardiology, General Hospital of Chinese People's Liberation Army

Beijing, Beijing Municipality, China

Site Status

Institute of Geriatric Cardiology

Beijing, Beijing Municipality, China

Site Status

Countries

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China

Central Contacts

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Tong Yin, Dr.

Role: CONTACT

Phone: 86-13693693085

Email: [email protected]

Lanning Zhang, Dr.

Role: CONTACT

Phone: 86-18611161208

Email: [email protected]

Facility Contacts

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Tong Yin, Doctor

Role: primary

Tong Yin, Dr.

Role: primary

References

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Zhang L, Chen Y, Jin Y, Qu F, Li J, Ma C, Yang J, Xu B, Wang H, Li X, Li Y, Zhang Y, Lu C, Yin T. Genetic determinants of high on-treatment platelet reactivity in clopidogrel treated Chinese patients. Thromb Res. 2013 Jul;132(1):81-7. doi: 10.1016/j.thromres.2013.05.006. Epub 2013 May 29.

Reference Type BACKGROUND
PMID: 23726091 (View on PubMed)

Other Identifiers

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2012042

Identifier Type: -

Identifier Source: org_study_id