Clopidogrel Pharmacogenetic Score System

Acute Coronary Syndrome Clinical Trial

— CPASS  

Official title:

Clopidogrel Pharmacogenetic Score System Established for Chinese Patients

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01990989
• Other study ID #: 2012042
• Status: Not yet recruiting
• Phase: N/A
• First received: November 18, 2013
• Last updated: November 18, 2013
• Start date: January 2014
• Est. completion date: January 2015

Study information

• Verified date: November 2013
• Source: Chinese PLA General Hospital
• Contact: Tong Yin, Dr.
• Phone: 86-13693693085
• Email: yintong2000[@]yahoo.com
• Is FDA regulated: No
• Health authority: China: National Natural Science Foundation
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 500
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Acute Coronary Syndrome

Locations

Country	Name	City	State
China	Institute of Geriatric Cardiology	Beijing	Beijing
China	Institute of Geriatric Cardiology, General Hospital of Chinese People's Liberation Army	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Chinese PLA General Hospital

Country where clinical trial is conducted

China, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	high on-treatment platelet reactivity (HPR)	A threshold of 50% maximal post-procedural aggregation was chosen to define HPR.	After 30 days maintenance dose of clopidogrel administration	No
Secondary	Composite ischemia cardiovascular outcomes	The composite of death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke , urgent coronal revascularization,and stent thrombosis.	1 year	No
Secondary	Hemorrhagic complications	The primary clinical safety end point of the study is the 1-year incidence of combined major and minor bleeding events defined according to the Thrombolysis in Myocardial Infarction (TIMI) criteria . TIMI major bleedings include hemoglobin reduction >5 g/dL(with or without obvious bleeding spots) , intracranial hemorrhages, and cardiac tamponade.TIMI minor bleedings include hemoglobin reduction >3 g/dL but =5 g/dL ,macroscopic hematuria,hemoptysis,hematemesis,ecchymoma,mucous membrane and other minor bleedings.	1 year	Yes