Status:

COMPLETED

Effect of Evolocumab in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke

Lead Sponsor:

Amgen

Conditions:

Coronary Heart Disease (CHD)

Eligibility:

All Genders

50-79 years

Phase:

PHASE3

Brief Summary

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 ...

Eligibility Criteria

Inclusion

  • Inclusion criteria:
  • 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).
  • 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) \<0.85.
  • 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\^2.
  • Coronary artery calcification score ≥300 in a participant without a coronary revascularization prior to randomization.
  • Exclusion criteria
  • MI or stroke prior to randomization.
  • CABG ˂ 3 months prior to screening.
  • eGFR ˂ 15 mL/min/1.73 m\^2.
  • 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.

Exclusion

    Key Trial Info

    Start Date :

    June 11 2019

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ACTUAL

    End Date :

    July 25 2025

    Estimated Enrollment :

    12301 Patients enrolled

    Trial Details

    Trial ID

    NCT03872401

    Start Date

    June 11 2019

    End Date

    July 25 2025

    Last Update

    November 10 2025

    Active Locations (852)

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    Page 1 of 213 (852 locations)

    1

    North Alabama Research Center LLC

    Athens, Alabama, United States, 35611

    2

    Cardiovascular Associates

    Birmingham, Alabama, United States, 35243

    3

    Heart Center Research LLC

    Huntsville, Alabama, United States, 35801

    4

    Mobile Heart Specialists PC

    Mobile, Alabama, United States, 36608