Personalization of Long-Term Antiplatelet Therapy - RAPID EXTEND (RAPID EXTEND)

January 12, 2024 updated by: Ottawa Heart Institute Research Corporation

Personalization of Long-Term Antiplatelet Therapy Using a Novel Combined Demographic/Pharmacogenomic Strategy - The RAPID EXTEND Randomized Study

In patients after myocardial infarction (MI) (heart attacks) and treated with percutaneous coronary intervention (PCI), the current standard is dual antiplatelet therapy (DAPT), with aspirin and a P2Y12 receptor inhibitor, for 1 year of treatment. At 1 year, there are several options including: i) Ongoing DAPT (with aspirin and ticagrelor), ii) Selective treatment use of a P2Y12 inhibitor based on risk profiles.

This study is a pilot vanguard study to evaluate several strategies for choosing anti-platelet regimen among patients post MI and PCI at 1 year.

Study Overview

Detailed Description

The present study is a pilot/vanguard 3-arm study that seeks to compare 3 possible strategies for patients that are 1 year post MI and PCI. The 3 randomized groups include: i) aspirin and ticagrelor 60 mg twice daily, ii) monotherapy with ticagrelor 60 mg twice daily and iii) a personalized arm (PA), where patients will get selective therapy based on demographic and genetic risks.

The PA group will use a modified DAPT score based on patient demographics to decide whether P2Y12 treatment is warranted. For those patients where treatment is warranted, a bedside genetic test will be used to determine whether they are carriers of at-risk genotypes, which put them at risk for under-responsiveness to clopidogrel (one of the specific P2Y12 inhibitors). Those identified as carriers will be treated with ticagrelor while non-carriers will be treated with clopidogrel.

The study will act as a vanguard study to prove feasibility of enrollment and document overall bleeding rates. The long-term goal of the study is determine whether a personalized approach will decrease bleeding versus an approach of DAPT with ticagrelor and versus an approach with ticagrelor monotherapy.

Study Type

Interventional

Enrollment (Estimated)

390

Phase

  • Phase 4

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

    • Ontario
      • Ottawa, Ontario, Canada, K1Y4W7
        • 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

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • >50 years old at 1-year after myocardial infarction (non-ST-elevation myocardial infarction (NSTEMI) or ST-elevation myocardial infarction (STEMI)) during which they had percutaneous coronary intervention (PCI)
  • Compliant with dual antiplatelet therapy (DAPT) for ≥ 1 year without an ischemic or bleeding complication after PCI
  • Still on DAPT regimen at enrollment
  • Patients must have 1 of the following atherothrombotic risk enrichment criteria:

    i) Age≥ 65 years ii) Diabetes iii) 2nd Prior MI (>1 year ago) iv) multi-vessel coronary disease v) creatinine clearance (CrCl) <60 mL/min.

Exclusion Criteria:

  • Intolerance to ticagrelor or clopidogrel
  • >18 months post percutaneous coronary intervention (PCI) and myocardial infarction (MI)
  • Requirement of a P2Y12 inhibitor
  • Requirement of oral anticoagulation
  • Take concurrent CYP3A inducing drugs which may interact with ticagrelor (e.g. anti-epileptic drugs)
  • History of stroke, TIA or intracranial bleed
  • Recent GI bleed or major surgery
  • Life expectancy of < 1 year
  • Platelet count < 100,000/μl
  • Bleeding diathesis
  • On dialysis
  • Severe liver disease
  • At risk for bradycardia.

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: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: DAPT - Aspirin and Ticagrelor
As per results of the PEGASUS trial, patients will be treated with aspirin 81mg daily and ticagrelor 60mg twice daily
DAPT with aspirin and ticagrelor
Other Names:
  • ASA, Brilinta
Experimental: Ticagrelor Monotherapy
Patients will only receive ticagrelor 60mg twice daily.
Ticagrelor monotherapy
Other Names:
  • Brilinta
Experimental: Personalized Therapy Arm
Patients allocated to the personalized arm (PA) will have a DAPT score calculated. For those with a score of < 2, only aspirin at 81 mg daily will be prescribed. For those with a score of ≥ 2, P2Y12 inhibitor choice will be dependent on carrier status of CYP2C19 LOF alleles. Heterozygous or homozygous carriers will receive be prescribed ticagrelor 60mg twice daily and non-carriers with will be prescribed clopidogrel 75mg daily.
Personalized therapy based on risk score and genotyping
Other Names:
  • ASA, Brilinta, Plavix

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bleeding Academic Research Consortium (BARC) Bleeding
Time Frame: 2 years post randomization
BARC bleeding types 2,3 or 5
2 years post randomization
Feasibility for Patient Enrollment and Follow-up - measured by number of patients enrolled and followed over 2 years
Time Frame: 2 years
Number of participants enrolled and followed: Target of 260 patients over 2 years with over 90% follow-up (Vanguard Study target)
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Thrombolysis in Myocardial Infarction (TIMI) bleeding
Time Frame: 1-3 years post randomization
Incidence of TIMI bleeding - major and minor
1-3 years post randomization
Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) bleeding
Time Frame: 1-3 years post randomization
Incidence of GUSTO bleeding - severe, moderate, mild
1-3 years post randomization
All Cause Mortality
Time Frame: 1 - 3 years post randomization
Death due to any cause
1 - 3 years post randomization
Cardiovascular Mortality
Time Frame: 1 -3 years post randomization
Death due to cardiovascular cause
1 -3 years post randomization
Myocardial Infarction
Time Frame: 1 -3 years post randomization
Myocardial infarction as defined by the 3rd universal definition on infarction
1 -3 years post randomization
Stroke
Time Frame: 1-3 years
Strokes defined as focal neurological deficit of >24 hrs and confirmed by imaging
1-3 years
Stent Thrombosis
Time Frame: 1 - 3 years post randomization
Probable and definite stent thrombosis per ARC definition
1 - 3 years post randomization

Collaborators and Investigators

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

Investigators

  • Principal Investigator: Derek YF So, MD FRCPC, 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 (Actual)

August 22, 2019

Primary Completion (Estimated)

March 1, 2024

Study Completion (Estimated)

September 1, 2024

Study Registration Dates

First Submitted

October 15, 2018

First Submitted That Met QC Criteria

November 1, 2018

First Posted (Actual)

November 2, 2018

Study Record Updates

Last Update Posted (Actual)

January 16, 2024

Last Update Submitted That Met QC Criteria

January 12, 2024

Last Verified

January 1, 2024

More Information

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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