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

April 23, 2013 updated by: Derek So, Ottawa Heart Institute Research Corporation

ReAssessment of Anti-Platelet Therapy Using an InDividualized Strategy in Patients With ST-segment Elevation Myocardial Infarction

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Dual anti-platelet therapy following percutaneous coronary intervention (PCI) for the treatment of STEMI has traditionally consisted of aspirin and clopidogrel. Despite this treatment approach, a substantial portion of patients experience recurrent adverse cardiovascular events including death, myocardial infarction, and stent thrombosis. This persistent vulnerability has been associated with inadequate platelet inhibition in response to clopidogrel administration, a phenomenon referred to as high on-treatment platelet reactivity. Although multiple variables have been implicated in altered clopidogrel response, mounting evidence has suggested a crucial role for common genetic variants including: CYP2C19*2, *17, and ABCB1 3435 C>T alleles.

Presence of the CYP2C19*2 allele has been associated with a 1.5- to 6-fold increased risk of cardiovascular death, myocardial infarction, and stent thrombosis following PCI in patients treated with clopidogrel. These findings, recently bolstered by 2 separate meta-analyses, led the American Food and Drug Administration to issue a boxed warning for clopidogrel stating that poor metabolizers may not receive the full benefit of the drug. The ABCB1 3435 TT genotype has also been linked with increased adverse cardiovascular events in individuals treated with clopidogrel following PCI for an acute coronary syndrome. In contrast, the CYP2C19*17 gain-of-function allele appears to enhance the activity of clopidogrel and has been associated with reduced ischemic events but increased bleeding.

As a result of these findings, experts have begun to advocate for routine genotyping in the context of PCI. A personalized approach to dual anti-platelet therapy following PCI is feasible given the presence of treatment alternatives such as prasugrel that are capable of overcoming clopidogrel resistance. Selective administration of prasugrel to patients at increased risk of clopidogrel resistance has the potential to successfully minimize adverse ischemic events, while simultaneously minimizing associated bleeding events and health care costs. A prospective pharmacogenomic approach to anti-platelet therapy has been previously hampered by limited access and the time-delay associated with genetic testing. The development of point-of-care genetic testing for the CYP2C19*2, *17, and ABCB1 3435 C>T alleles that requires minimal training to perform carries the potential to overcome these obstacles and may facilitate the incorporation of pharmacogenetic strategies into routine clinical practice.

Patients receiving PCI in the context of STEMI will undergo point-of-care genetic testing for the CYP2C19*2, *17, and ABCB1 3435 C>T alleles. CYP2C19*2 carriers and individuals homozygous for the ABCB1 3435 T allele will subsequently be randomized to prasugrel 10mg daily for 1 month or clopidogrel 150mg daily for 1 week followed by 75mg daily. The remaining individuals without an at-risk genotype will receive standard therapy with clopidogrel. At the end of the 1 month period, efficacy of the treatment strategies will be evaluated using VerifyNow platelet function testing. The effect of the CYP2C19*17 allele will be prospectively evaluated during the treatment period.

Study Type

Interventional

Enrollment (Actual)

102

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Ottawa, Ontario, Canada, K1N 4W7
        • University of Ottawa Heart Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: At-Risk Genetics Arm: Prasugrel
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
Point-of-Care Genetic Testing for Genetic Variants Linked to Adverse Outcomes with Clopidogrel (CYP2C19*2 & ABCB1 3435 TT)
Other Names:
  • Spartan RX
Drug: Prasugrel
Treatment of STEMI patients carrying at least one high risk genetic variant with prasugrel 10mg daily.
Other Names:
  • Effient
Active Comparator: At-Risk Genetics Arm: Clopidogrel
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
Point-of-Care Genetic Testing for Genetic Variants Linked to Adverse Outcomes with Clopidogrel (CYP2C19*2 & ABCB1 3435 TT)
Other Names:
  • Spartan RX
Active Comparator: Low Risk Genetics Arm: Clopidogrel
Treatment of STEMI patients with no at-risk genetic variants with clopidogrel 75mg daily.
Genetic: Point-of-Care Genetic Testing
Point-of-Care Genetic Testing for Genetic Variants Linked to Adverse Outcomes with Clopidogrel (CYP2C19*2 & ABCB1 3435 TT)
Other Names:
  • Spartan RX

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Time Frame: 1 month
High on-treatment platelet reactivity as measured by the VerifyNow P2Y12 assay with evidence based cutoffs.
1 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite of death from cardiovascular causes, non-fatal myocardial infarction, and re-hospitalization.
Time Frame: 1 month
1 month
Bleeding risk
Time Frame: 1 month
Defined by TIMI major/minor
1 month
Concordance of point-of-care genetic screening with laboratory based genotyping methods
Time Frame: 1 month
Genotyping results from the Spartan RX device will be compared with the results of direct DNA sequencing.
1 month
Effect of the CYP2C19*17 allele on platelet inhibition.
Time Frame: 1 month
As measured by VerifyNow in P2Y12 Reaction Units (PRU) and percent platelet inhibition.
1 month
Effect of CYP2C19*17 allele on bleeding events
Time Frame: 1 month
Comparison of TIMI major & minor bleeding rates in carriers and non-carriers of the CYP2C19*17 allele.
1 month
Mean PRU and percent platelet inhibition in CYP2C19*2 and ABCB1 3435 TT carriers treated with prasugrel relative to clopidogrel
Time Frame: 1 month
1 month
Between-group change in PRU and percent platelet inhibition in CYP2C19*2 and ABCB1 3435 TT carriers treated with prasugrel relative to clopidogrel.
Time Frame: 1 month
1 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ottawa Heart Institute Research Corporation

Collaborators

Spartan Bioscience Inc.

Investigators

  • Principal Investigator: Derek Y F So, MD, Ottawa Heart Institute Research Corporation
  • Study Director: Jason D Roberts, MD, Ottawa Heart Institute Research Corporation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2011

Primary Completion (Actual)

September 1, 2012

Study Completion (Actual)

March 1, 2013

Study Registration Dates

First Submitted

September 27, 2011

First Submitted That Met QC Criteria

October 11, 2011

First Posted (Estimate)

October 14, 2011

Study Record Updates

Last Update Posted (Estimate)

April 25, 2013

Last Update Submitted That Met QC Criteria

April 23, 2013

Last Verified

April 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2010364-01H

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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