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Genotype Guided Versus Conventional Approach in Selection of Oral P2Y12 Receptor Blocker in Chinese Patients Suffering From Acute Coronary Syndrome

Sponsor
The University of Hong Kong (Other)
Overall Status
Completed
CT.gov ID
NCT01994941
Collaborator
(none)
133
Enrollment
1
Location
2
Arms
24
Duration (Months)
5.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study aims to compare the outcome between genotype guided versus clinical guided approach in selection of oral P2Y12 receptor blocker in Chinese patients suffering from acute coronary syndrome.

Condition or Disease Intervention/Treatment Phase
Phase 4

Detailed Description

Acute coronary syndrome (ACS) is a disease with high mortality, morbidity and economic burden. Usually, it is caused by ischemic heart disease and atherosclerotic plaque rupture in the coronary arteries causing platelet activation, aggregation and thrombus formation. For decades, antiplatelet agents are the cornerstones of management of ACS and dual antiplatelet therapy with aspirin and P2Y12 receptor blocker are standard of care for patients with ACS with or without percutaneous coronary intervention. However, increasing evidence has shown that clopidogrel, which is a type of thienopyridine, has wide inter-individual variability in pharmacokinetic and pharmacodynamic actions which lead to suboptimal antiplatelet effect especially in Asian population. Cytochrome P450 2C19 is an important enzyme for thienopyridine metabolism and genetic polymorphisms of CYP2C19 have been demonstrated to be associated with clopidogrel resistance and ischemic event post percutaneous coronary intervention (1-3). The prevalence of the LOF allele of CYP2C19 is higher in Chinese than in Caucasians (4) and it may lead to the higher degree of clopidogrel resistance in Chinese patients as documented in our previous study (5) and study from another Asian country (6)

In view of the potential limitations of clopidogrel in ACS treatment, American and European guidelines recommend use of newer P2Y12 blockers such as ticagrelor (7) for ACS patients. Though these agents have better anti-ischemic effect, they are associated with increased bleeding risk especially in Chinese patients whom are considered to be more prone to bleeding complications. As a result, local physicians are reluctant in using these potent antiplatelet agents despite their proven clinical efficacy in Caucasian studies. Evidence has shown the correlation between CYP2C19 genotype, platelet reactivity, clinical outcome and currently CYP2C19 genotype is an emerging target in the pharmacogenomic approach in guiding the use of antiplatelet agents. With the advent of rapid genotyping technologies (8), it is anticipated that the appropriate drug can be given to the appropriate patient.

Verigene (Nanosphere, Northbrook, IL) is an FDA approved microarray-based genotyping assay for the rapid detection of cytochrome P450 2C19 polymorphisms from whole blood using nanoparticle probes. It utilises whole blood for detection of single nucleotide polymorphism and the results will be available in 2-4 hours. With proper training and handling, the accuracy is expected to be >99%. (9, 10)

Study Design

Study Type:
Interventional
Actual Enrollment :
133 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Genotype Guided Versus Conventional Approach in Selection of Oral P2Y12 Receptor Blocker in Chinese Patients Suffering From Acute Coronary Syndrome
Study Start Date :
Aug 1, 2013
Actual Primary Completion Date :
Aug 1, 2015
Actual Study Completion Date :
Aug 1, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: Genotype guided group

Patients are given standard doses of clopidogrel (either 300mg or 600mg according to clinical protocol). Blood will be drawn for rapid genetic testing (Verigene) and results will be expected in 2-4 hours. If patients are intermediate or poor clopidogrel metabolisers, loading dose of ticagrelor 180mg are given to enhance the antiplatelet response. Apart from the approach in guiding the use of P2Y12 receptor blocker, all patients will be treated according to usual clinical care including medications and coronary intervention. Blood will also be sent to standard laboratory for CYP2C19 genotyping using conventional polymerase chain reaction (PCR) method so as to confirm the accuracy of rapid genetic test. 24 hours after initial clopidogrel loading, blood will be taken to measure platelet reactivity by verifyNow P2Y12 assay (Accumetrics). In case glycoprotein IIbIIIa inhibitor (Integrilin) is used, verifyNow P2Y12 assay will be performed 48 hours after cessation of Integrilin.

Drug: Clopidogrel
A platelet aggregation inhibitor. Also a P2Y12 Receptor Blocker of a drug class Thienopyridine. Increasing evidence has shown that clopidogrel has wide inter-individual variability in pharmacokinetic and pharmacodynamic actions which lead to suboptimal antiplatelet effect especially in Asian population. A standard loading dose of 300mg or 600mg(according to clinical protocol) will be given to patients.
Other Names:
  • Plavix

    • Drug: Ticagrelor
    A platelet aggregation inhibitor. Though this agent has better anti-ischemic effects, it is associated with increased bleeding risk especially in Chinese patients whom are considered to be more prone to bleeding complications. A loading dose of 180mg will be used.
    Other Names:
  • Brilinta

    		•
    Active Comparator: Clinical guided group

    Patients are given standard doses of clopidogrel (either 300mg or 600mg according to clinical protocol). Apart from the approach in guiding the use of P2Y12 receptor blocker, all patients will be treated according to usual clinical care including medications and coronary intervention. Blood will also be sent to standard laboratory for CYP2C19 genotyping using conventional polymerase chain reaction (PCR) method so as to confirm the accuracy of rapid genetic test. 24 hours after initial clopidogrel loading, blood will be taken to measure platelet reactivity by verifyNow P2Y12 assay (Accumetrics) which is an FDA approved, point-of-care device using light-transmission based optical detection which measures platelet aggregation. In case glycoprotein IIbIIIa inhibitor (Integrilin) is used, verifyNow P2Y12 assay will be performed 48 hours after cessation of Integrilin.

    Drug: Clopidogrel
    A platelet aggregation inhibitor. Also a P2Y12 Receptor Blocker of a drug class Thienopyridine. Increasing evidence has shown that clopidogrel has wide inter-individual variability in pharmacokinetic and pharmacodynamic actions which lead to suboptimal antiplatelet effect especially in Asian population. A standard loading dose of 300mg or 600mg(according to clinical protocol) will be given to patients.
    Other Names:
  • Plavix

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Platelet reactivity 24 hours after initial loading of clopidogrel measured by verifyNow P2Y12 assay [24 hours]

      Platelet reactivity 24 hours after initial loading of clopidogrel measured by verifyNow P2Y12 assay

    2. Platelet reactivity 1 month after initial loading of clopidogrel measured by verifyNow P2Y12 assay [1 month]

      Platelet reactivity 1 month after initial loading of clopidogrel measured by verifyNow P2Y12 assay

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Age of 18 years or above

    • Diagnosis of Acute Coronary Syndrome

    • P2Y12 receptor blocker naïve and planning for a loading dose of P2Y12 receptor blocker

    Exclusion Criteria:

    • Chronic renal failure on dialysis or plan for dialysis within 1 year

    • Serious hepatic disease

    • Active bleeding disorder

    • Contraindicated or allergic to Clopidogrel or ticagrelor

    • History of intracranial bleeding

    • Women who are pregnant or who are of childbearing potential who do not use adequate contraception

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Department of Medicine, the University of Hong Kong, Queen Mary Hospital, Hospital Authority Hong Kong Hong Kong

    Sponsors and Collaborators

    • The University of Hong Kong

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Professor Stephen Lee, Prof. Stephen Lee, The University of Hong Kong
    ClinicalTrials.gov Identifier:
    NCT01994941
    Other Study ID Numbers:
    • UW 13-402
    First Posted:
    Nov 26, 2013
    Last Update Posted:
    Dec 2, 2015
    Last Verified:
    Nov 1, 2015
    Keywords provided by Professor Stephen Lee, Prof. Stephen Lee, The University of Hong Kong
    Acute Coronary Syndrome
    Platelet Reactivity
    P2Y12 Receptor Blocker
    CYP2C19 Genotyping
    Additional relevant MeSH terms:
    Acute Coronary Syndrome
    Syndrome
    Clopidogrel
    Ticagrelor

    Study Results

    No Results Posted as of Dec 2, 2015