Personalization of Long-Term Antiplatelet Therapy Using a Novel Combined Demographic/Pharmacogenomic Strategy - The RAPID EXTEND Randomized Study
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 39
- 试验地点
- 2
- 主要终点
- Bleeding Academic Research Consortium (BARC) Bleeding
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Investigator, Outcomes Assessor)
盲法说明
Double (Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •>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.
排除标准
- •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.
研究组 & 干预措施
Ticagrelor Monotherapy
Patients will only receive ticagrelor 60mg twice daily.
干预措施: Ticagrelor Monotherapy: Ticagrelor 60 mg twice daily (Drug)
DAPT - Aspirin and Ticagrelor
As per results of the PEGASUS trial, patients will be treated with aspirin 81mg daily and ticagrelor 60mg twice daily
干预措施: Active Comparator: Dual Antiplatelet Therapy (DAPT) - Aspirin 81 mg + Ticagrelor 60mg twice daily (Drug)
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.
干预措施: Personalized Therapy Arm: Aspirin 81 mg or Ticagrelor 60mg twice daily or Clopidogrel 75 mg once daily (Drug)
结局指标
主要结局
Bleeding Academic Research Consortium (BARC) Bleeding
时间窗: 2 years post randomization
BARC bleeding types 2,3 or 5
Feasibility for Patient Enrollment and Follow-up - measured by number of patients enrolled and followed over 2 years
时间窗: 2 years
Number of participants enrolled and followed: Target of 260 patients over 2 years with over 90% follow-up (Vanguard Study target)
次要结局
- Thrombolysis in Myocardial Infarction (TIMI) bleeding(1-3 years post randomization)
- Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) bleeding(1-3 years post randomization)
- All Cause Mortality(1 - 3 years post randomization)
- Cardiovascular Mortality(1 -3 years post randomization)
- Myocardial Infarction(1 -3 years post randomization)
- Stroke(1-3 years)
- Stent Thrombosis(1 - 3 years post randomization)