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

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ClinicalTrials.gov Identifier: NCT03729401
Recruitment Status : Not yet recruiting
First Posted : November 2, 2018
Last Update Posted : July 9, 2019
Sponsor:
Information provided by (Responsible Party):
Ottawa Heart Institute Research Corporation

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Coronary Artery Disease Myocardial Infarction Drug: Active Comparator: Dual Antiplatelet Therapy (DAPT) - Aspirin 81 mg + Ticagrelor 60mg twice daily Drug: Ticagrelor Monotherapy: Ticagrelor 60 mg twice daily Drug: Personalized Therapy Arm: Aspirin 81 mg or Ticagrelor 60mg twice daily or Clopidogrel 75 mg once daily Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 390 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Masking Description: Double (Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Personalization of Long-Term Antiplatelet Therapy Using a Novel Combined Demographic/Pharmacogenomic Strategy - The RAPID EXTEND Randomized Study
Estimated Study Start Date : July 2019
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : October 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Attack

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
Drug: Active Comparator: Dual Antiplatelet Therapy (DAPT) - Aspirin 81 mg + Ticagrelor 60mg twice daily
DAPT with aspirin and ticagrelor
Other Name: ASA, Brilinta

Experimental: Ticagrelor Monotherapy
Patients will only receive ticagrelor 60mg twice daily.
Drug: Ticagrelor Monotherapy: Ticagrelor 60 mg twice daily
Ticagrelor monotherapy
Other Name: 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.
Drug: Personalized Therapy Arm: Aspirin 81 mg or Ticagrelor 60mg twice daily or Clopidogrel 75 mg once daily
Personalized therapy based on risk score and genotyping
Other Name: ASA, Brilinta, Plavix




Primary Outcome Measures :
  1. Bleeding Academic Research Consortium (BARC) Bleeding [ Time Frame: 2 years post randomization ]
    BARC bleeding types 2,3 or 5

  2. 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)


Secondary Outcome Measures :
  1. Thrombolysis in Myocardial Infarction (TIMI) bleeding [ Time Frame: 1-3 years post randomization ]
    Incidence of TIMI bleeding - major and minor

  2. 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

  3. All Cause Mortality [ Time Frame: 1 - 3 years post randomization ]
    Death due to any cause

  4. Cardiovascular Mortality [ Time Frame: 1 -3 years post randomization ]
    Death due to cardiovascular cause

  5. Myocardial Infarction [ Time Frame: 1 -3 years post randomization ]
    Myocardial infarction as defined by the 3rd universal definition on infarction

  6. Stroke [ Time Frame: 1-3 years ]
    Strokes defined as focal neurological deficit of >24 hrs and confirmed by imaging

  7. Stent Thrombosis [ Time Frame: 1 - 3 years post randomization ]
    Probable and definite stent thrombosis per ARC definition



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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03729401


Contacts
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Contact: Poppy MacPhee, BScN 6136967000 ext 14646 pmacphee@ottawaheart.ca

Sponsors and Collaborators
Ottawa Heart Institute Research Corporation
Investigators
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Principal Investigator: Derek YF So, MD FRCPC Ottawa Heart Institute Research Corporation

Publications:
Levine GN, Bates ER, Bittl JA, Brindis RG, Fihn SD, Fleisher LA, Granger CB, Lange RA, Mack MJ, Mauri L, Mehran R, Mukherjee D, Newby LK, O'Gara PT, Sabatine MS, Smith PK, Smith SC Jr. 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease, 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction, 2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes, and 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery. Circulation. 2016 Sep 6;134(10):e123-55. doi: 10.1161/CIR.0000000000000404. Epub 2016 Mar 29. Review. Erratum in: Circulation. 2016 Sep 6;134(10):e192-4.

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Responsible Party: Ottawa Heart Institute Research Corporation
ClinicalTrials.gov Identifier: NCT03729401     History of Changes
Other Study ID Numbers: 20180593
First Posted: November 2, 2018    Key Record Dates
Last Update Posted: July 9, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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

Keywords provided by Ottawa Heart Institute Research Corporation:
1-year post myocardial infarction
P2Y12 inhibitor
antiplatelet regimen

Additional relevant MeSH terms:
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Aspirin
Clopidogrel
Infarction
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Ticagrelor
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors