Pharmacogenetic Approach to Anti-platelet Therapy for the Treatment of ST-segment Elevation Myocardial Infarction (STEMI)

NCT01452139 | Completed Phase 2 DMC

• 1 other identifier: 2010364-01H
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of the RAPID STEMI study is to evaluate the feasibility, efficacy, and safety of a pharmacogenetic approach to anti-platelet therapy for the treatment of ST-segment elevation myocardial infarction (STEMI) patients following percutaneous coronary intervention (PCI) using point-of-care genetic testing for the CYP2C19\*2, \*17, and ABCB1 3435 C\>T alleles.

Conditions

STEMI

Keywords

STEMI; Pharmacogenetics; Prasugrel; Clopidogrel; Percutaneous Coronary Intervention

Outcome Measures

Primary Outcomes (1)

• The rates of high on-treatment platelet reactivity as measured by the VerifyNow P2Y12 assay (Accumetrics, San Diego, CA) in CYP2C19*2 and ABCB1 3435 TT carriers treated with prasugrel relative to clopidogrel.

  High on-treatment platelet reactivity as measured by the VerifyNow P2Y12 assay with evidence based cutoffs.

  1 month

Secondary Outcomes (7)

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

  1 month

• Bleeding risk

  1 month

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

  1 month

• Effect of the CYP2C19*17 allele on platelet inhibition.

  1 month

• Effect of CYP2C19*17 allele on bleeding events

  1 month

Study Arms (3)

At-Risk Genetics Arm: Prasugrel

EXPERIMENTAL

Treatment of STEMI patients carrying at least 1 at-risk genetic variant with prasugrel 10mg daily for 1 month.

Genetic: Point-of-Care Genetic Testing; Drug: Prasugrel

At-Risk Genetics Arm: Clopidogrel

ACTIVE COMPARATOR

Treatment of STEMI patients carrying at least 1 at-risk genetic variant with clopidogrel 150mg daily for 1 week followed by 75mg daily.

Genetic: Point-of-Care Genetic Testing

Low Risk Genetics Arm: Clopidogrel

ACTIVE COMPARATOR

Treatment of STEMI patients with no at-risk genetic variants with clopidogrel 75mg daily.

Genetic: Point-of-Care Genetic Testing

Interventions

Point-of-Care Genetic Testing GENETIC

Point-of-Care Genetic Testing for Genetic Variants Linked to Adverse Outcomes with Clopidogrel (CYP2C19\*2 \& ABCB1 3435 TT)

Also known as: Spartan RX

At-Risk Genetics Arm: Clopidogrel; At-Risk Genetics Arm: Prasugrel; Low Risk Genetics Arm: Clopidogrel

Prasugrel DRUG

Treatment of STEMI patients carrying at least one high risk genetic variant with prasugrel 10mg daily.

Also known as: Effient

At-Risk Genetics Arm: Prasugrel

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
• STEMI patients treated with percutaneous coronary intervention
• Able to provide informed consent
• Able to comply with assigned treatment strategy and attend 1 month follow-up visit

You may not qualify if:

• Receiving anti-platelet therapy other than aspirin and clopidogrel
• Receiving anti-coagulation with warfarin or dabigatran
• History of stroke or transient ischemic attack
• Platelet count \< 100 000/μL
• Known Bleeding Diathesis
• Hematocrit \<30% 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, K1N 4W7, Canada

Location

Related Publications (9)

• 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

• 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

• 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

• Mega JL, Close SL, Wiviott SD, Shen L, Walker JR, Simon T, Antman EM, Braunwald E, Sabatine MS. Genetic variants in ABCB1 and CYP2C19 and cardiovascular outcomes after treatment with clopidogrel and prasugrel in the TRITON-TIMI 38 trial: a pharmacogenetic analysis. Lancet. 2010 Oct 16;376(9749):1312-9. doi: 10.1016/S0140-6736(10)61273-1.

  PMID: 20801494 BACKGROUND

• 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

• 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

• Marcucci R, Gori AM, Paniccia R, Giusti B, Valente S, Giglioli C, Buonamici P, Antoniucci D, Abbate R, Gensini GF. Cardiovascular death and nonfatal myocardial infarction in acute coronary syndrome patients receiving coronary stenting are predicted by residual platelet reactivity to ADP detected by a point-of-care assay: a 12-month follow-up. Circulation. 2009 Jan 20;119(2):237-42. doi: 10.1161/CIRCULATIONAHA.108.812636. Epub 2008 Dec 31.

  PMID: 19118249 BACKGROUND

• Sibbing D, Koch W, Gebhard D, Schuster T, Braun S, Stegherr J, Morath T, Schomig A, von Beckerath N, Kastrati A. Cytochrome 2C19*17 allelic variant, platelet aggregation, bleeding events, and stent thrombosis in clopidogrel-treated patients with coronary stent placement. Circulation. 2010 Feb 2;121(4):512-8. doi: 10.1161/CIRCULATIONAHA.109.885194. Epub 2010 Jan 18.

  PMID: 20083681 BACKGROUND

MeSH Terms

Conditions

ST Elevation Myocardial Infarction

Interventions

Prasugrel Hydrochloride

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

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: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 27, 2011
• First Posted: October 14, 2011
• Study Start: September 1, 2011
• Primary Completion: September 1, 2012
• Study Completion: March 1, 2013
• Last Updated: April 25, 2013

Record last verified: 2013-04

Locations

CA (1)