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)

• Sponsor: Amarin Pharma Inc.
• Information provided by (Responsible Party): Amarin Pharma Inc.

Tracking Information

• First Submitted Date: December 13, 2011
• First Posted Date: December 15, 2011
• Last Update Posted Date: October 16, 2018
• Actual Study Start Date: November 2011
• Actual Primary Completion Date: May 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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 (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 (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 Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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: 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: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Cardiovascular Diseases

Intervention

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 12, 2018): 8179
• Original Estimated Enrollment (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

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: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, India, Netherlands, New Zealand, Poland, Romania, Russian Federation, South Africa, Ukraine, United States

Administrative Information

• NCT Number: NCT01492361
• Other Study ID Numbers: 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: Amarin Pharma Inc.
• Collaborators: Not Provided

Investigators

• 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