ReAssessment of Anti-Platelet Therapy Using an InDividualized Strategy Based on GENetic Evaluation

NCT01184300 | Completed Phase 2

• 1 other identifier: HC-9427-U0143-43C
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of the RAPID GENE study is to evaluate the feasibility, efficacy and safety of a pharmacogenomic approach to anti-platelet therapy following coronary artery stenting using a CYP2C19\*2 point-of-care genetic test.

Conditions

Stable Coronary Artery Disease; Acute Coronary Syndrome; Percutaneous Coronary Intervention

Keywords

CYP2C19*2; Pharmacogenomics; Clopidogrel; Prasugrel; Percutaneous Coronary Intervention

Outcome Measures

Primary Outcomes (1)

• Clopidogrel response status as measured by the VerifyNow P2Y12 assay (Accumetrics, San Diego, CA) in CYP2C19*2 carriers.

  Response status defined in P2Y12 Reaction Units (PRU) and percent platelet inhibition.

  1 week

Secondary Outcomes (6)

• Concordance of point-of-care genetic screening with laboratory based genotyping methods

  1 week

• Composite of death from cardiovascular causes, non-fatal myocardial infarction, and re-hospitalization

  1 week and 6 months

• Bleeding risk

  1 week and 6 months

• Incidence of stent thrombosis

  1 week and 6 months

• Feasibility of point-of-care genotyping in randomized setting

  1 week

Study Arms (2)

Rapid Genotyping

EXPERIMENTAL

Patients randomized to the Rapid Genotyping arm will have their CYP2C19\*2 carrier status determined at the time of percutaneous coronary intervention with subsequent alteration in anti-platelet therapy for \*2 carriers.

Genetic: Point-of-care genetic screening with subsequent prasugrel administration to CYP2C19*2 carriers

Standard Therapy

NO INTERVENTION

Patients randomized to the Standard Therapy arm will not undergo genotyping at the time of percutaneous coronary intervention. All patients will receive clopidogrel 75 mg daily for 1 week. At the end of the 1 week period, their CYP2C19\*2 carrier status will be verified.

Interventions

Point-of-care genetic screening with subsequent prasugrel administration to CYP2C19*2 carriers GENETIC

Patients found to carry the CYP2C19\*2 allele will receive prasugrel 10 mg daily for 1 week. Non-carriers will receive clopidogrel 75 mg daily.

Also known as: Prasugrel (Effient)

Rapid Genotyping

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and Females between the ages of 18 and 75 years
• Patients undergoing percutaneous coronary intervention in the context of a non-ST-elevation acute coronary syndrome or stable coronary artery disease
• Able to provide informed consent
• Able to comply with assigned treatment strategy and attend 1 week follow-up visit

You may not qualify if:

• Receiving anti-platelet therapy other than aspirin and clopidogrel
• Receiving anti-coagulation with warfarin
• History of stroke or transient ischemic attack
• Platelet count \< 100 000/μL
• Known Bleeding Diathesis
• Hematocrit \<32% or \>52%
• Severe Liver Dysfunction
• Renal Insufficiency (Creatinine Clearance \< 30ml/min)
• Pregnant females

Sponsors & Collaborators

• Ottawa Heart Institute Research Corporation: lead
• Spartan Bioscience Inc.: collaborator

Study Sites (1)

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y 4W7, Canada

Location

Related Publications (8)

• Damani SB, Topol EJ. The case for routine genotyping in dual-antiplatelet therapy. J Am Coll Cardiol. 2010 Jul 6;56(2):109-11. doi: 10.1016/j.jacc.2010.03.029. Epub 2010 May 13.

  PMID: 20471193 BACKGROUND

• Hulot JS, Collet JP, Silvain J, Pena A, Bellemain-Appaix A, Barthelemy O, Cayla G, Beygui F, Montalescot G. Cardiovascular risk in clopidogrel-treated patients according to cytochrome P450 2C19*2 loss-of-function allele or proton pump inhibitor coadministration: a systematic meta-analysis. J Am Coll Cardiol. 2010 Jul 6;56(2):134-43. doi: 10.1016/j.jacc.2009.12.071.

  PMID: 20620727 BACKGROUND

• Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, Walker JR, Antman EM, Macias W, Braunwald E, Sabatine MS. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009 Jan 22;360(4):354-62. doi: 10.1056/NEJMoa0809171. Epub 2008 Dec 22.

  PMID: 19106084 BACKGROUND

• Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, Walker JR, Antman EM, Macias WL, Braunwald E, Sabatine MS. Cytochrome P450 genetic polymorphisms and the response to prasugrel: relationship to pharmacokinetic, pharmacodynamic, and clinical outcomes. Circulation. 2009 May 19;119(19):2553-60. doi: 10.1161/CIRCULATIONAHA.109.851949. Epub 2009 May 4.

  PMID: 19414633 BACKGROUND

• Price MJ, Endemann S, Gollapudi RR, Valencia R, Stinis CT, Levisay JP, Ernst A, Sawhney NS, Schatz RA, Teirstein PS. Prognostic significance of post-clopidogrel platelet reactivity assessed by a point-of-care assay on thrombotic events after drug-eluting stent implantation. Eur Heart J. 2008 Apr;29(8):992-1000. doi: 10.1093/eurheartj/ehn046. Epub 2008 Feb 10.

  PMID: 18263931 BACKGROUND

• Trenk D, Hochholzer W, Fromm MF, Chialda LE, Pahl A, Valina CM, Stratz C, Schmiebusch P, Bestehorn HP, Buttner HJ, Neumann FJ. Cytochrome P450 2C19 681G>A polymorphism and high on-clopidogrel platelet reactivity associated with adverse 1-year clinical outcome of elective percutaneous coronary intervention with drug-eluting or bare-metal stents. J Am Coll Cardiol. 2008 May 20;51(20):1925-34. doi: 10.1016/j.jacc.2007.12.056.

  PMID: 18482659 BACKGROUND

• Sibbing D, Stegherr J, Latz W, Koch W, Mehilli J, Dorrler K, Morath T, Schomig A, Kastrati A, von Beckerath N. Cytochrome P450 2C19 loss-of-function polymorphism and stent thrombosis following percutaneous coronary intervention. Eur Heart J. 2009 Apr;30(8):916-22. doi: 10.1093/eurheartj/ehp041. Epub 2009 Feb 4.

  PMID: 19193675 BACKGROUND

• Roberts JD, Wells GA, Le May MR, Labinaz M, Glover C, Froeschl M, Dick A, Marquis JF, O'Brien E, Goncalves S, Druce I, Stewart A, Gollob MH, So DY. Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): a prospective, randomised, proof-of-concept trial. Lancet. 2012 May 5;379(9827):1705-11. doi: 10.1016/S0140-6736(12)60161-5. Epub 2012 Mar 29.

  PMID: 22464343 DERIVED

MeSH Terms

Conditions

Acute Coronary Syndrome

Interventions

Prasugrel Hydrochloride

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Derek Y.F. So, MD

  Ottawa Heart Institute Research Corporation

  PRINCIPAL INVESTIGATOR

• Jason D. Roberts, MD

  Ottawa Heart Institute Research Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2010
• First Posted: August 18, 2010
• Study Start: August 1, 2010
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: November 11, 2011

Record last verified: 2011-11

Locations

CA (1)