A Study of AMR101 to Evaluate Its Ability to Reduce Cardiovascular Events in High Risk Patients With Hypertriglyceridemia and on Statin. The Primary Objective is to Evaluate the Effect of 4 g/Day AMR101 for Preventing the Occurrence of a First Major Cardiovascular Event. (REDUCE-IT)

Study Description

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Brief Summary:

AMR101 (icosapent ethyl [ethyl-EPA]) is a highly purified ethyl ester of eicosapentaenoic acid (EPA) being developed by Amarin Pharma Inc. for the treatment of cardiovascular disease in statin-treated patients with hypertriglyceridemia. The purpose of this study is 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.

Condition or disease	Intervention/treatment	Phase
Cardiovascular Diseases	Drug: AMR101; Drug: Placebo	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	8179 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:	Prevention
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)
Actual Study Start Date :	November 2011
Actual Primary Completion Date :	May 2018
Actual Study Completion Date :	May 2018

Arms and Interventions

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Arm	Intervention/treatment
Experimental: AMR101	Drug: AMR101; Parallel Assignment; Other Name: VASCEPA® (icosapent ethyl)
Placebo Comparator: Placebo	Drug: Placebo; Parallel Assignment

Outcome Measures

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Primary Outcome Measures :

1. Composite of CV death, nonfatal MI (including silent MI), nonfatal stroke, coronary revascularization, and unstable angina determined to be caused by myocardial ischemia by invasive / non-invasive testing and requiring emergent hospitalization. [ Time Frame: 4-6 years ]
   Time from randomization to the first occurrence of any component of the composite of the following clinical events: CV death, nonfatal MI (including silent MI), nonfatal stroke, coronary revascularization, and unstable angina determined to be caused by myocardial ischemia by invasive / non-invasive testing and requiring emergent hospitalization.

Secondary Outcome Measures :

1. Composite of CV death, nonfatal MI (including silent MI), or nonfatal stroke. [ Time Frame: 4-6 years ]
   Key secondary outcome measure is the time from randomization to the first occurrence of the composite of CV death, nonfatal MI (including silent MI), or nonfatal stroke.
2. Composite of CV death or nonfatal MI (including silent MI). [ Time Frame: 4-6 years ]
   Time from randomization to the first occurrence of the composite of CV death or nonfatal MI (including silent MI).
3. Fatal or nonfatal MI (including silent MI). [ Time Frame: 4-6 years ]
   Time from randomization to the first occurrence of fatal or nonfatal MI (including silent MI).
4. Non-elective coronary revascularization represented as the composite of emergent or urgent classifications. [ Time Frame: 4-6 years ]
   Time from randomization to the first occurrence of non-elective coronary revascularization represented as the composite of emergent or urgent classifications.
5. CV death. [ Time Frame: 4-6 years ]
   Time from randomization to the occurrence of CV death.
6. Unstable angina determined to be caused by myocardial ischemia by invasive / non-invasive testing and requiring emergent hospitalization. [ Time Frame: 4-6 years ]
   Time from randomization to the first occurrence of unstable angina determined to be caused by myocardial ischemia by invasive / non-invasive testing and requiring emergent hospitalization.
7. Fatal or nonfatal stroke. [ Time Frame: 4-6 years ]
   Time from randomization to the first occurrence of fatal or nonfatal stroke.
8. Total mortality, nonfatal MI (including silent MI), or nonfatal stroke. [ Time Frame: 4-6 years ]
   Time from randomization to the first occurrence of the composite of total mortality, nonfatal MI (including silent MI), or nonfatal stroke.
9. Total mortality. [ Time Frame: 4-6 years. ]
   Time from randomization to the occurrence of death from any cause.

Eligibility Criteria

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Ages Eligible for Study:	45 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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  Show 410 Study Locations

Sponsors and Collaborators

Amarin Pharma Inc.

Investigators

Principal Investigator:	Deepak L. Bhatt, MD, MPH	Brigham and Women's Hospital, 75 Francis Street, Boston

More Information

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Publications:

Bhatt DL, Steg PG, Brinton EA, Jacobson TA, Miller M, Tardif JC, Ketchum SB, Doyle RT Jr, Murphy SA, Soni PN, Braeckman RA, Juliano RA, Ballantyne CM; REDUCE-IT Investigators. Rationale and design of REDUCE-IT: Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial. Clin Cardiol. 2017 Mar;40(3):138-148. doi: 10.1002/clc.22692. Epub 2017 Mar 15.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT Jr, Juliano RA, Jiao L, Granowitz C, Tardif JC, Ballantyne CM; REDUCE-IT Investigators. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019 Jan 3;380(1):11-22. doi: 10.1056/NEJMoa1812792. Epub 2018 Nov 10.

Responsible Party:	Amarin Pharma Inc.
ClinicalTrials.gov Identifier:	NCT01492361 History of Changes
Other Study ID Numbers:	AMR-01-01-0019
First Posted:	December 15, 2011
Last Update Posted:	October 16, 2018
Last Verified:	October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

Keywords provided by Amarin Pharma Inc.:

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; EPA; Docosahexaenoic Acid; Fish; Fatty acids; Fibrates; Niacin; Lipids; Lipoprotein; Atorvastatin; Lovaza; Simvastatin; Lovastatin

Additional relevant MeSH terms:

Cardiovascular Diseases; Hypertriglyceridemia; Hyperlipidemias; Dyslipidemias	Lipid Metabolism Disorders; Metabolic Diseases; Eicosapentaenoic acid ethyl ester; Platelet Aggregation Inhibitors