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)

• ClinicalTrials.gov Identifier: NCT01492361
• Recruitment Status: Completed
• First Posted: December 15, 2011
• Last Update Posted: June 6, 2019
• 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: June 6, 2019
• 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 ]

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.
• Peterson BE, Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Juliano RA, Jiao L, Doyle RT Jr, Granowitz C, Gibson CM, Pinto D, Giugliano RP, Budoff MJ, Tardif JC, Verma S, Ballantyne CM; REDUCE-IT Investigators. Reduction in Revascularization with Icosapent Ethyl: Insights from REDUCE-IT REVASC. Circulation. 2020 Nov 5. doi: 10.1161/CIRCULATIONAHA.120.050276. [Epub ahead of print]
• Bhatt DL, Miller M, Brinton EA, Jacobson TA, Steg PG, Ketchum SB, Doyle RT Jr, Juliano RA, Jiao L, Granowitz C, Tardif JC, Olshansky B, Chung MK, Gibson CM, Giugliano RP, Budoff MJ, Ballantyne CM; REDUCE-IT Investigators. REDUCE-IT USA: Results From the 3146 Patients Randomized in the United States. Circulation. 2020 Feb 4;141(5):367-375. doi: 10.1161/CIRCULATIONAHA.119.044440. Epub 2019 Nov 11.
• Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT Jr, Juliano RA, Jiao L, Granowitz C, Tardif JC, Gregson J, Pocock SJ, Ballantyne CM; REDUCE-IT Investigators. Effects of Icosapent Ethyl on Total Ischemic Events: From REDUCE-IT. J Am Coll Cardiol. 2019 Jun 11;73(22):2791-2802. doi: 10.1016/j.jacc.2019.02.032. Epub 2019 Mar 18.
• 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: June 2019