A Study of AMR101 to Evaluate Its Ability to Reduce Cardiovascular Events in High-Risk Patients With Hypertriglyceridemia and on Statin

Study Overview
=================
Brief Summary
-----------------
AMR101 (icosapent ethyl [ethyl-EPA]) is a highly purified ethyl ester of eicosapentaenoic acid (EPA) developed by Amarin Pharma Inc. for the treatment of cardiovascular disease in statin-treated patients with hypertriglyceridemia. The purpose of this study was to evaluate whether this drug, combined with a statin therapy, will be superior to the statin therapy alone, when used as a prevention in reducing long-term cardiovascular events in high-risk patients with mixed dyslipidemia.

Official Title
-----------------
Evaluation of the Effect of AMR101 on Cardiovascular Health and Mortality in Hypertriglyceridemic Patients With Cardiovascular Disease or at High Risk for Cardiovascular Disease: REDUCE-IT (Reduction of Cardiovascular Events With EPA - Intervention Trial)

Conditions
-----------------
Cardiovascular Diseases

Intervention / Treatment
-----------------
* Drug: AMR101
* Drug: Placebo
* Drug: Statin therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and non-pregnant or sterile women ages 45 and older Hypertriglyceridemia On statin therapy for at least four weeks Either having established cardiovascular disease or at high risk for cardiovascular disease Exclusion Criteria: Severe heart failure Any life-threatening disease other than cardiovascular disease Active severe liver disease Hemoglobin A1c >10.0% Poorly controlled hypertension Planned coronary intervention (such as stent placement or heart bypass) or any non-cardiac major surgical procedure Known familial lipoprotein lipase deficiency (Fredrickson Type I), apolipoprotein C-II deficiency, or familial dysbetalipoproteinemia (Fredrickson Type III) Known hypersensitivity to the study product, fish and/or shellfish, or placebo History of acute or chronic pancreatitis Patients are excluded if using the following medications: PCSK9 inhibitors niacin >200 mg/day or fibrates; any omega-3 fatty acid medications ; dietary supplements containing omega-3 fatty acids (e.g., flaxseed oil, fish oil, krill oil, or algal oil); bile acid sequestrants

Ages Eligible for Study
-----------------
Minimum Age: 45 Years

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

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

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

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMR101<br>AMR101 (icosapent ethyl) + statin therapy, daily | Drug: AMR101<br>* Parallel Assignment<br>* Other names: VASCEPA® (icosapent ethyl);Drug: Statin therapy<br>* Stable statin therapy (± ezetimibe) for at least 28 days before lipid qualification measurement (LDL-C >40 mg/dL and ≤100 mg/dL)<br>|
| Placebo Comparator: Placebo<br>Placebo + statin therapy, daily | Drug: Placebo<br>* Parallel Assignment<br>* Other names: matching placebo;Drug: Statin therapy<br>* Stable statin therapy (± ezetimibe) for at least 28 days before lipid qualification measurement (LDL-C >40 mg/dL and ≤100 mg/dL)<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of CV Death, Nonfatal MI (Including Silent MI), Nonfatal Stroke, Coronary Revascularization, or Unstable Angina Determined to be Caused by Myocardial Ischemia by Invasive / Non-invasive Testing and Requiring Emergent Hospitalization. | The primary outcome measure was the number of patients with a first occurrence of any component of the composite of CV death, nonfatal MI (including silent MI), nonfatal stroke, coronary revascularization, or unstable angina determined to be caused by myocardial ischemia by invasive / non-invasive testing and requiring emergent hospitalization during the follow-up period. | Total follow-up time of up to approximately 6 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of CV Death, Nonfatal MI (Including Silent MI), or Nonfatal Stroke. | The key secondary outcome measure was the number of patients with a first occurrence of any component of the composite of CV death, nonfatal MI (including silent MI), or nonfatal stroke during the follow-up period. | Total follow-up time of up to approximately 6 years. | 
| Composite of CV Death or Nonfatal MI (Including Silent MI). | Number of patients with a first occurrence of any component of the composite of CV death or nonfatal MI (including silent MI) during the follow-up period. | Total follow-up time of up to approximately 6 years. | 
| Fatal or Nonfatal MI (Including Silent MI). | Number of patients with a first occurrence of fatal or nonfatal MI (including silent MI) during the follow-up period. | Total follow-up time of up to approximately 6 years. | 
| Non-elective Coronary Revascularization Represented as the Composite of Emergent or Urgent Classifications. | Number of patients with a first occurrence of non-elective coronary revascularization represented as the composite of emergent or urgent classifications during the follow-up period. | Total follow-up time of up to approximately 6 years. | 
| CV Death. | Number of patients with an occurrence of CV death during the follow-up period. | Total follow-up time of up to approximately 6 years. | 
| Unstable Angina Determined to be Caused by Myocardial Ischemia by Invasive / Non-invasive Testing and Requiring Emergent Hospitalization. | Number of patients with a first occurrence of unstable angina determined to be caused by myocardial ischemia by invasive / non-invasive testing and requiring emergent hospitalization during the follow-up period. | Total follow-up time of up to approximately 6 years. | 
| Fatal or Nonfatal Stroke. | Number of patients with a first occurrence of fatal or nonfatal stroke during the follow-up period. | Total follow-up time of up to approximately 6 years. | 
| Total Mortality, Nonfatal MI (Including Silent MI), or Nonfatal Stroke. | Number of patients with a first occurrence of any component of the composite of total mortality, nonfatal MI (including silent MI), or nonfatal stroke during the follow-up period. | Total follow-up time of up to approximately 6 years. | 
| Total Mortality. | Number of patients with an occurrence of death from any cause during the follow-up period. | Total follow-up time of up to approximately 6 years. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
EPA, Rosuvastatin, Coronary Artery Disease, Myocardial Ischemia, Coronary Disease, Heart Diseases, Acute Coronary Syndrome, Cardiovascular Diseases, Arteriosclerosis, Arterial Occlusive Diseases, Vascular Diseases, Angina Pectoris, Chest Pain, Anticholesteremic Agents, Hypolipidemic Agents, Lipid Regulating Agents, Hypertriglyceridemia, Omega-3 Fatty Acids, Statin, Triglycerides, Docosahexaenoic Acid, Fish, Fatty acids, Fibrates, Niacin, Lipids, Lipoprotein, Atorvastatin, Lovaza, Simvastatin, Lovastatin, Pravastatin, Fluvastatin, Trilipix, Vytorin, Simcor, Ezetimibe, Zetia, Ethyl-EPA, Ethyl Icosapentate, Crestor, Zocor, Lipitor, LDL, HDL, Cholesterol, Dyslipidemia, AMR101, Cardiovascular Disease, Unspecified, VASCEPA, Icosapent Ethyl