Personalization of Long-Term Antiplatelet Therapy - RAPID EXTEND

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Coronary Artery Disease, Myocardial Infarction

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: DAPT - Aspirin and Ticagrelor<br>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<br>* DAPT with aspirin and ticagrelor<br>* Other names: ASA, Brilinta;|
| Experimental: Ticagrelor Monotherapy<br>Patients will only receive ticagrelor 60mg twice daily. | Drug: Ticagrelor Monotherapy: Ticagrelor 60 mg twice daily<br>* Ticagrelor monotherapy<br>* Other names: Brilinta;|
| Experimental: Personalized Therapy Arm<br>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<br>* Personalized therapy based on risk score and genotyping<br>* Other names: ASA, Brilinta, Plavix;|

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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1-year post myocardial infarction, P2Y12 inhibitor, antiplatelet regimen