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

NCT01994941 | Completed Phase 4 DMC

• 1 other identifier: UW 13-402
• Study Type: interventional
• Target: 133
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Coronary Syndrome

Keywords

Acute Coronary Syndrome; Platelet Reactivity; P2Y12 Receptor Blocker; CYP2C19 Genotyping

Outcome Measures

Primary Outcomes (2)

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

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

  24 hours

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

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

  1 month

Study Arms (2)

Genotype guided group

EXPERIMENTAL

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; Drug: Ticagrelor

Clinical guided group

ACTIVE COMPARATOR

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

Interventions

Clopidogrel DRUG

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.

Also known as: Plavix

Clinical guided group; Genotype guided group

Ticagrelor DRUG

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.

Also known as: Brilinta

Genotype guided group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

Department of Medicine, the University of Hong Kong, Queen Mary Hospital, Hospital Authority

Hong Kong, Hong Kong

Location

Related Publications (9)

• Mega JL, Simon T, Collet JP, Anderson JL, Antman EM, Bliden K, Cannon CP, Danchin N, Giusti B, Gurbel P, Horne BD, Hulot JS, Kastrati A, Montalescot G, Neumann FJ, Shen L, Sibbing D, Steg PG, Trenk D, Wiviott SD, Sabatine MS. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA. 2010 Oct 27;304(16):1821-30. doi: 10.1001/jama.2010.1543.

  PMID: 20978260 BACKGROUND

• Shuldiner AR, O'Connell JR, Bliden KP, Gandhi A, Ryan K, Horenstein RB, Damcott CM, Pakyz R, Tantry US, Gibson Q, Pollin TI, Post W, Parsa A, Mitchell BD, Faraday N, Herzog W, Gurbel PA. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA. 2009 Aug 26;302(8):849-57. doi: 10.1001/jama.2009.1232.

  PMID: 19706858 BACKGROUND

• Simon T, Verstuyft C, Mary-Krause M, Quteineh L, Drouet E, Meneveau N, Steg PG, Ferrieres J, Danchin N, Becquemont L; French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) Investigators. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med. 2009 Jan 22;360(4):363-75. doi: 10.1056/NEJMoa0808227. Epub 2008 Dec 22.

  PMID: 19106083 BACKGROUND

• Myrand SP, Sekiguchi K, Man MZ, Lin X, Tzeng RY, Teng CH, Hee B, Garrett M, Kikkawa H, Lin CY, Eddy SM, Dostalik J, Mount J, Azuma J, Fujio Y, Jang IJ, Shin SG, Bleavins MR, Williams JA, Paulauskis JD, Wilner KD. Pharmacokinetics/genotype associations for major cytochrome P450 enzymes in native and first- and third-generation Japanese populations: comparison with Korean, Chinese, and Caucasian populations. Clin Pharmacol Ther. 2008 Sep;84(3):347-61. doi: 10.1038/sj.clpt.6100482. Epub 2008 Mar 19.

  PMID: 18231117 BACKGROUND

• Chan MY, Tan K, Tan HC, Huan PT, Li B, Phua QH, Lee HK, Lee CH, Low A, Becker RC, Ong WC, Richards MA, Salim A, Tai ES, Koay E. CYP2C19 and PON1 polymorphisms regulating clopidogrel bioactivation in Chinese, Malay and Indian subjects. Pharmacogenomics. 2012 Apr;13(5):533-42. doi: 10.2217/pgs.12.24.

  PMID: 22462746 BACKGROUND

• Chae H, Kim M, Koh YS, Hwang BH, Kang MK, Kim Y, Park HI, Chang K. Feasibility of a microarray-based point-of-care CYP2C19 genotyping test for predicting clopidogrel on-treatment platelet reactivity. Biomed Res Int. 2013;2013:154073. doi: 10.1155/2013/154073. Epub 2013 Mar 28.

  PMID: 23607088 BACKGROUND

• Buchan BW, Peterson JF, Cogbill CH, Anderson DK, Ledford JS, White MN, Quigley NB, Jannetto PJ, Ledeboer NA. Evaluation of a microarray-based genotyping assay for the rapid detection of cytochrome P450 2C19 *2 and *3 polymorphisms from whole blood using nanoparticle probes. Am J Clin Pathol. 2011 Oct;136(4):604-8. doi: 10.1309/AJCPCPU9Q2IRNYXC.

  PMID: 21917683 BACKGROUND

• Bernlochner I, Mayer K, Morath T, Orban M, Schulz S, Schomig A, Braun S, Kastrati A, Sibbing D. Antiplatelet efficacy of prasugrel in patients with high on-clopidogrel treatment platelet reactivity and a history of coronary stenting. Thromb Haemost. 2013 Mar;109(3):517-24. doi: 10.1160/TH12-08-0552. Epub 2013 Jan 17.

  PMID: 23328965 BACKGROUND

• Tam CC, Kwok J, Wong A, Yung A, Shea C, Kong SL, Tang WH, Siu D, Chan R, Lee S. Genotyping-guided approach versus the conventional approach in selection of oral P2Y12 receptor blockers in Chinese patients suffering from acute coronary syndrome. J Int Med Res. 2017 Feb;45(1):134-146. doi: 10.1177/0300060516677190. Epub 2016 Dec 22.

  PMID: 28222641 DERIVED

MeSH Terms

Conditions

Acute Coronary Syndrome

Interventions

Clopidogrel; Ticagrelor

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Adenosine; Purine Nucleosides; Purines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Stephen Lee

Study Record Dates

• First Submitted: November 20, 2013
• First Posted: November 26, 2013
• Study Start: August 1, 2013
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: December 2, 2015

Record last verified: 2015-11

Locations

HK (1)