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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by The University of Hong Kong
Sponsor:
Information provided by (Responsible Party):
Prof. Stephen Lee, The University of Hong Kong
ClinicalTrials.gov Identifier:
NCT01994941
First received: November 20, 2013
Last updated: November 28, 2013
Last verified: November 2013
  Purpose

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 Intervention Phase
Acute Coronary Syndrome
Drug: Clopidogrel
Drug: Ticagrelor
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by The University of Hong Kong:

Primary Outcome Measures:
  • Platelet reactivity 24 hours after initial loading of clopidogrel measured by verifyNow P2Y12 assay [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Platelet reactivity 1 month after initial loading of clopidogrel measured by verifyNow P2Y12 assay


Estimated Enrollment: 200
Study Start Date: August 2013
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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

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)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01994941

Contacts
Contact: Shun Ling Kong, MN MSc(Stat) (852) 6087 2006 kongsl@hku.hk

Locations
Hong Kong
Department of Medicine, the University of Hong Kong, Queen Mary Hospital, Hospital Authority Recruiting
Hong Kong, Hong Kong
Contact: Shun Ling Kong, MN MSc(Stat)    (852) 6087 2006    kongsl@hku.hk   
Principal Investigator: Stephen WL Lee, MD FRCP FACC         
Sub-Investigator: Frankie CC Tam, MD         
Sub-Investigator: Kelvin KW Chan, MD         
Sub-Investigator: Michael PH Chan, MD         
Sub-Investigator: David CW Siu, MD         
Sub-Investigator: Janette SY Kwok, MD         
Sub-Investigator: Linda LT Lam, MD         
Sub-Investigator: Yui Ming Lam, MD         
Sub-Investigator: Raymond HW Chan, MD         
Sponsors and Collaborators
The University of Hong Kong
  More Information

Publications:

Responsible Party: Prof. Stephen Lee, The University of Hong Kong
ClinicalTrials.gov Identifier: NCT01994941     History of Changes
Other Study ID Numbers: UW 13-402
Study First Received: November 20, 2013
Last Updated: November 28, 2013
Health Authority: Hong Kong: Ethics Committee

Keywords provided by The University of Hong Kong:
Acute Coronary Syndrome
Platelet Reactivity
P2Y12 Receptor Blocker
CYP2C19 Genotyping

Additional relevant MeSH terms:
Platelet Aggregation Inhibitors
Acute Coronary Syndrome
Syndrome
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Angina Pectoris
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms
Disease
Pathologic Processes
Clopidogrel
Ticagrelor
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 16, 2014