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)

Tracking Information
First Submitted Date ICMJE	December 13, 2011
First Posted Date ICMJE	December 15, 2011
Last Update Posted Date	October 16, 2018
Actual Study Start Date ICMJE	November 2011
Actual Primary Completion Date	May 2018 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: October 12, 2018)	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.
Original Primary Outcome Measures ICMJE; (submitted: December 13, 2011)	Incidence of cardiovascular events, such as coronary revascularization. [ Time Frame: 4-6 years ]
Change History	Complete list of historical versions of study NCT01492361 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: October 12, 2018)	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.; 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).; 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).; 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.; CV death. [ Time Frame: 4-6 years ]Time from randomization to the occurrence of CV death.; 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.; Fatal or nonfatal stroke. [ Time Frame: 4-6 years ]Time from randomization to the first occurrence of fatal or nonfatal stroke.; 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.; Total mortality. [ Time Frame: 4-6 years. ]Time from randomization to the occurrence of death from any cause.
Original Secondary Outcome Measures ICMJE; (submitted: December 13, 2011)	Incidence of additional cardiovascular events, lipid and lipoprotein levels, subgroup analyses such as: diabetics, etc. [ Time Frame: 4-6 years ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	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.
Official Title ICMJE	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)
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.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Prevention
Condition ICMJE	Cardiovascular Diseases
Intervention ICMJE	Drug: AMR101 Parallel Assignment Other Name: VASCEPA® (icosapent ethyl); Drug: Placebo Parallel Assignment
Study Arms	Experimental: AMR101 Intervention: Drug: AMR101; Placebo Comparator: Placebo Intervention: Drug: Placebo
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.; 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.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: October 12, 2018)	8179
Original Estimated Enrollment ICMJE; (submitted: December 13, 2011)	8000
Actual Study Completion Date	May 2018
Actual Primary Completion Date	May 2018 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	45 Years and older (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Australia, Canada, India, Netherlands, New Zealand, Poland, Romania, Russian Federation, South Africa, Ukraine, United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01492361
Other Study ID Numbers ICMJE	AMR-01-01-0019
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Plan to Share IPD: Undecided
Responsible Party	Amarin Pharma Inc.
Study Sponsor ICMJE	Amarin Pharma Inc.
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Deepak L. Bhatt, MD, MPH Brigham and Women's Hospital, 75 Francis Street, Boston
PRS Account	Amarin Pharma Inc.
Verification Date	October 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP