NCT03872401已完成3 期
A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Impact of Evolocumab on Major Cardiovascular Events in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 12,301
- 试验地点
- 1,694
- 主要终点
- Time to Coronary Heart Disease Death, Myocardial Infarction, or Ischemic Stroke
研究概览
简要总结
This study will assess the effect of lowering low-density lipoprotein cholesterol (LDL-C) with evolocumab on major cardiovascular events in adults without a prior myocardial infarction (MI) or stroke who are at high risk of a cardiovascular event.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: Adult participants ≥ 50 (men) or ≥ 55 (women) to ˂ 80 years of age (either sex) and meeting lipid criteria.
- •Lipid Criteria: Low-density lipoprotein cholesterol (LDL-C) ≥ 90 mg/dL (≥ 2.3 mmol/L) or non high-density lipoprotein cholesterol (non-HDL)-C ≥ 120 mg/dL (≥ 3.1 mmol/L), or apolipoprotein B ≥ 80 mg/dL (≥ 1.56 µmol/L).
- •3.Diagnostic evidence of at least one of the following (A-D) at screening:
- •A.Significant coronary artery disease (CAD) meeting at least 1 of the following criteria:
- •History of coronary revascularization with multi-vessel coronary disease as evidenced by any of the following:
- •percutaneous coronary intervention (PCI) of 2 or more vessels, including branch arteries,
- •PCI or coronary artery bypass grafting (CABG) with residual 50% stenosis in a separate, unrevascularized vessel, or
- •multi-vessel CABG 5 years or more prior to screening.
- •Significant coronary disease without prior revascularization as evidenced by either a ≥70% stenosis of at least 1 coronary artery, ≥50% stenosis of 2 or more coronary arteries, or ≥50% stenosis of the left main coronary artery.
- •known coronary artery calcium score ≥100 in participants without a coronary artery revascularization prior to randomization.
- •B. Significant atherosclerotic cerebrovascular disease meeting at least 1 of the following criteria:
- •prior transient ischemic attack with ≥50% carotid stenosis.
- •internal or external carotid artery stenosis of ≥70% or 2 or more ≥50% stenoses.
- •prior internal or external carotid artery revascularization.
- •C. Significant peripheral arterial disease meeting at least 1 of the following criteria:
- •≥50% stenosis in a limb artery.
- •history of abdominal aorta treatment (percutaneous and surgical) due to atherosclerotic disease.
- •ankle brachial index (ABI) <0.
- •D. Diabetes mellitus with at least 1 of the following:
- •known microvascular disease, defined by diabetic nephropathy or treated retinopathy. Diabetic nephropathy defined as persistent microalbuminuria (urinary albumin to creatinine ratio ≥30mg/g) and/or persistent estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m^2 that is not reversible due to an acute illness.
- •chronic daily treatment with an intermediate or long-acting insulin.
- •diabetes diagnosis ≥10 years ago.
- •At least 1 of the following 1 high-risk criteria (most recent lab values within 6 months prior to screening, as applicable):
- •Polyvascular disease, defined as coronary, carotid, or peripheral artery stenosis ≥50% in a second distinct vascular location in a participant with coronary, cerebral or peripheral arterial disease (A, B, or C above).
- •Presence of either diabetes mellitus or metabolic syndrome in a participant with coronary, cerebral, or peripheral artery disease (A, B, or C above).
- •At least 1 coronary, carotid, or peripheral artery residual stenosis of ≥50% in a participant with diabetes meeting inclusion criterion (D above).
- •LDL-C ≥130 mg/dL (≥3.36 mmol/L), OR non-HDL-C ≥160 mg/dL (≥4.14 mmol/L), OR apolipoprotein B ≥120 mg/dL (2.3 µmol/L) if available.
- •Lipoprotein (a) >125 nmol/L (50 mg/dL).
- •Known familial hypercholesterolemia.
- •Family history of premature coronary artery disease defined as an MI or CABG in the participant's father or brother at age <55 years or an MI or CABG in the participant's mother or sister at age <60 years.
- •High sensitive c-reactive protein (hsCRP) ≥3.0 mg/L in the absence of an acute illness.
- •Current tobacco use.
- •≥65 years of age.
- •Menopause before 40 years of age.
- •eGFR 15 to <45 mL/min/1.73 m^
- •Coronary artery calcification score ≥300 in a participant without a coronary revascularization prior to randomization.
排除标准
- •MI or stroke prior to randomization.
- •CABG ˂ 3 months prior to screening.
- •eGFR ˂ 15 mL/min/1.73 m^
- •Uncontrolled or recurrent ventricular tachycardia in the absence of an implantable-cardioverter defibrillator.
- •Atrial fibrillation or atrial flutter not on anticoagulation therapy (vitamin K antagonist, heparin, low molecular weight heparin, fondaparinux,or non-Vitamin K antagonist oral anticoagulant).
- •Triglycerides ≥ 500 mg/dL (5.7 mmol/L) measured up to 3 months prior to screening. The most recent results must be used.
- •Last measured left-ventricular ejection fraction ˂ 30% or New York Heart Association (NYHA) Functional Class III/IV.
- •Planned arterial revascularization.
研究组 & 干预措施
Placebo
Placebo Comparator
Participants will receive placebo subcutaneous injection once every 2 weeks (Q2W).
干预措施: Placebo (Drug)
Evolocumab 140 mg Q2W
Experimental
Participants will receive 140 mg evolocumab by subcutaneous injection Q2W.
干预措施: Evolocumab (Drug)
结局指标
主要结局
Time to Coronary Heart Disease Death, Myocardial Infarction, or Ischemic Stroke
时间窗: From randomization; for approximately a median of 4.5 years
Time to coronary heart disease (CHD) death, myocardial infarction (MI), or ischemic stroke, whichever occurs first.
Time to Coronary Heart Disease Death, Myocardial Infarction, Ischemic Stroke, or Any Ischemia-driven Arterial Stroke
时间窗: From randomization; for approximately a median of 4.5 years
Time to CHD death, MI, ischemic stroke, or any ischemia-driven arterial revascularization, whichever occurs first.
次要结局
- Time to Cardiovascular Death(From randomization; for approximately a median of 4.5 years)
- Time to Ischemic Stroke(From randomization; for approximately a median of 4.5 years)
- Time to CHD Death, MI, or Any Ischemia-driven Arterial Revascularization(From randomization; for approximately a median of 4.5 years)
- Time to Cardiovascular Death, MI, or Ischemic Stroke(From randomization; for approximately a median of 4.5 years)
- Time to CHD Death or MI(From randomization; for approximately a median of 4.5 years)
- Time to All Cause of Death(From randomization; for approximately a median of 4.5 years)
- Time to CHD Death(From randomization; for approximately a median of 4.5 years)
- Time to MI, Ischemic Stroke, or Any Ischemia-driven Arterial Revascularization(From randomization; for approximately a median of 4.5 years)
- Time to Myocardial Infarction(From randomization; for approximately a median of 4.5 years)
- Time to Any Ischemia-driven Arterial Revascularization(From randomization; for approximately a median of 4.5 years)
研究者
研究点 (1694)
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