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

Study Overview
=================
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 who are at high risk of a cardiovascular event.

Official Title
-----------------
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

Conditions
-----------------
Coronary Heart Disease (CHD)

Intervention / Treatment
-----------------
* Drug: Evolocumab
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Age: Adult subjects ≥ 50 (men) or ≥ 55 (women) to ˂ 80 years of age (either sex) and meeting lipid criteria Low-density lipoprotein cholesterol (LDL-C) ≥ 90 mg/dL (≥ 2.3 mmol/L) or non-high-density lipoprotein cholesterol (non-HDL) ≥ 120 mg/dL (≥ 3.1 mmol/L), or apolipoprotein B ≥ 80 mg/dL (≥ 1.56 µmol/L) Evidence of at least one of the following at screening (without prior myocardial infarction or stroke): A. Significant coronary artery disease (CAD) B. Significant atherosclerotic cerebrovascular disease C. Significant peripheral arterial disease D. Diabetes mellitus At least 1 high-risk feature Exclusion criteria MI or stroke prior to randomization Coronary artery bypass grafting (CABG) ˂ 3 months prior to screening Estimated glomerular filtration rate (eGFR) ˂ 15 mL/min/1.73 m² 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

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 79 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants will receive placebo subcutaneous injection once every 2 weeks (Q2W). | Drug: Placebo<br>* Administered subcutaneously using an autoinjector pen.<br>|
| Experimental: Evolocumab 140 mg Q2W<br>Participants will receive 140 mg evolocumab by subcutaneous injection Q2W. | Drug: Evolocumab<br>* Administered subcutaneously using an autoinjector pen.<br>* Other names: Repatha;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Coronary Heart Disease Death, Myocardial Infarction, or Ischemic Stroke | Time to coronary heart disease (CHD) death, myocardial infarction (MI), or ischemic stroke, whichever occurs first. | From randomization; for approximately a median of 4.5 years | 
| Time to Coronary Heart Disease Death, Myocardial Infarction, Ischemic Stroke, or Any Ischemia-driven Arterial Sroke | Time to CHD death, MI, ischemic stroke, or any ischemia-driven arterial revascularization, whichever occurs first. | From randomization; for approximately a median of 4.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to MI, Ischemic Stroke, or Any Ischemia-driven Arterial Revascularization |  | 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 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 | 
| Time to CHD Death |  | From randomization; for approximately a median of 4.5 years | 
| Time to Cardiovascular Death |  | 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 Ischemic Stroke |  | From randomization; for approximately a median of 4.5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
High Cardiovascular Risk, No prior Myocardial Infarction stroke, >= 50 years of age (men), >= 55 years of age (women), lipid-lowering therapy