Genotype Guided Versus Conventional Approach in Selection of Oral P2Y12 Receptor Blocker in Chinese Patients Suffering From Acute Coronary Syndrome
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| ClinicalTrials.gov Identifier: NCT01994941 |
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Recruitment Status :
Completed
First Posted : November 26, 2013
Last Update Posted : December 2, 2015
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Acute Coronary Syndrome | Drug: Clopidogrel Drug: Ticagrelor | Phase 4 |
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 Type : | Interventional (Clinical Trial) |
| 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 : | August 2013 |
| Actual Primary Completion Date : | August 2015 |
| Actual Study Completion Date : | August 2015 |
| Arm | Intervention/treatment |
|---|---|
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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 Name: 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 Name: Brilinta |
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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 Name: Plavix |
- Platelet reactivity 24 hours after initial loading of clopidogrel measured by verifyNow P2Y12 assay [ Time Frame: 24 hours ]Platelet reactivity 24 hours after initial loading of clopidogrel measured by verifyNow P2Y12 assay
- Platelet reactivity 1 month after initial loading of clopidogrel measured by verifyNow P2Y12 assay [ Time Frame: 1 month ]Platelet reactivity 1 month after initial loading of clopidogrel measured by verifyNow P2Y12 assay
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01994941
| Hong Kong | |
| Department of Medicine, the University of Hong Kong, Queen Mary Hospital, Hospital Authority | |
| Hong Kong, Hong Kong | |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| 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: | November 26, 2013 Key Record Dates |
| Last Update Posted: | December 2, 2015 |
| Last Verified: | November 2015 |
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Acute Coronary Syndrome Platelet Reactivity P2Y12 Receptor Blocker CYP2C19 Genotyping |
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Acute Coronary Syndrome Syndrome Disease Pathologic Processes Myocardial Ischemia Heart Diseases Cardiovascular Diseases Vascular Diseases Clopidogrel |
Ticagrelor Platelet Aggregation Inhibitors Purinergic P2Y Receptor Antagonists Purinergic P2 Receptor Antagonists Purinergic Antagonists Purinergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs |