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Outcomes Study to Assess STatin Residual Risk Reduction With EpaNova in HiGh CV Risk PatienTs With Hypertriglyceridemia (STRENGTH)

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ClinicalTrials.gov Identifier: NCT02104817
Recruitment Status : Completed
First Posted : April 4, 2014
Results First Posted : July 28, 2021
Last Update Posted : August 17, 2021
Sponsor:
Collaborators:
The Cleveland Clinic
IQVIA RDS Inc.
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE April 2, 2014
First Posted Date  ICMJE April 4, 2014
Results First Submitted Date  ICMJE May 25, 2021
Results First Posted Date  ICMJE July 28, 2021
Last Update Posted Date August 17, 2021
Actual Study Start Date  ICMJE October 30, 2014
Actual Primary Completion Date May 27, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 8, 2021)
The Composite of Major Adverse Cardiovascular Events (MACE) [ Time Frame: From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure ]
MACE components include: cardiovascular (CV) death, nonfatal myocardial infarction (MI), nonfatal stroke, emergent/elective coronary revascularization, or hospitalization for unstable angina. Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed).
Original Primary Outcome Measures  ICMJE
 (submitted: April 2, 2014)
The primary outcome measure is the time to the first occurrence of any component of the composite of MACE. [ Time Frame: Patients will remain in the study until the required number of MACE has occurred. We anticipate that patients will be in the study for up to 5 years. ]
MACE components include: (cardiovascular death, nonfatal MI, nonfatal stroke, emergent/elective coronary revascularization, or hospitalization for unstable angina) in patients with persistent hypertriglyceridemia. The primary outcome measure is the time to first occurrence of any component of the composite of MACE (cardiovascular death, nonfatal MI, nonfatal stroke, emergent/elective coronary revascularization, or hospitalization for unstable angina) as estimated by a time to event analysis. The primary outcome will be analyzed for the intent-to-treat (ITT) population using adjudicated events.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 8, 2021)
  • The Composite of MACE in the Subgroup of Participants With Established CV Disease(CVD) at Baseline [ Time Frame: From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure ]
    MACE components include: cardiovascular (CV) death, nonfatal myocardial infarction (MI), nonfatal stroke, emergent/elective coronary revascularization, or hospitalization for unstable angina. Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed).
  • The Composite of CV Events [ Time Frame: From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure ]
    CV events include: cardiovascular (CV) death, non-fatal myocardial infarction (MI) and non-fatal stroke. Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed).
  • The Composite of CV Events in the Subgroup of Participants With Established CV Disease (CVD) at Baseline [ Time Frame: From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure ]
    CV events include: cardiovascular (CV) death, non-fatal myocardial infarction (MI) and non-fatal stroke. Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed).
  • The Composite of Coronary Events [ Time Frame: From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure ]
    Coronary events include: cardiac death (including death due to acute myocardial infarction, sudden cardiac death and death due to cardiovascular procedures), non-fatal myocardial infarction (MI), emergent/elective coronary revascularization and hospitalization for unstable angina. Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed).
  • The Composite of Coronary Events in the Subgroup of Participants With Established CVD at Baseline [ Time Frame: From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure ]
    Coronary events include: cardiac death (including death due to acute myocardial infarction, sudden cardiac death and death due to cardiovascular procedures), non-fatal myocardial infarction (MI), emergent/elective coronary revascularization and hospitalization for unstable angina. Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed) in the subgroup of participants with established CVD at baseline
  • CV Death [ Time Frame: From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure ]
    Participants with no observed events are censored at the latest of the date of last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed), last date known to be alive, and date of non-cardiovascular death.
  • CV Death in the Subgroup of Participants With Established CVD at Baseline [ Time Frame: From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure ]
    Participants with no observed events are censored at the latest of the date of last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed), last date known to be alive, and date of non-cardiovascular death in the subgroup of participants with established CVD at baseline
  • All-cause Death [ Time Frame: From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure ]
    Participants with no observed events are censored at the latest of the date of last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed) and last date known to be alive.
  • All-cause Death in the Subgroup of Participants With Established CVD at Baseline [ Time Frame: From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure ]
    Participants with no observed events are censored at the latest of the date of last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed) and last date known to be alive in the subgroup of participants with established CVD at baseline
Original Secondary Outcome Measures  ICMJE
 (submitted: April 2, 2014)
  • The first occurrence of any component of cardiovascular death, nonfatal MI, or nonfatal stroke [ Time Frame: We anticipate that patients will be in the study for up to 5 years. ]
    The secondary outcome measures will be analyzed the same as outlined above for the primary outcome measures. The secondary outcomes will be analyzed for the ITT population. If the primary endpoint objective is met, the secondary outcomes will be evaluated hierarchically at an alpha of 0.05 for each comparison.
  • The composite measure of coronary events that include the first occurrence of cardiovascular death, nonfatal MI, emergent/elective coronary revascularization, or hospitalization for unstable angina. [ Time Frame: We anticipate that patients will be in the study for up to 5 years. ]
    The secondary outcome measures will be analyzed the same as outlined above for the primary outcome measures. The secondary outcomes will be analyzed for the ITT population. If the primary endpoint objective is met, the secondary outcomes will be evaluated hierarchically at an alpha of 0.05 for each comparison.
  • The first occurrence of individual components of MACE: emergent/elective coronary revascularization, hospitalization for unstable angina, fatal or nonfatal MI, fatal or nonfatal stroke, cardiovascular death. [ Time Frame: We anticipate that patients will be in the study for up to 5 years ]
    MACE components include: (cardiovascular death, nonfatal MI, nonfatal stroke, emergent/elective coronary revascularization, or hospitalization for unstable angina) in patients with persistent hypertriglyceridemia. The secondary outcome measures will be analyzed the same as outlined above for the primary outcome measures. The secondary outcomes will be analyzed for the ITT population. If the primary endpoint objective is met, the secondary outcomes will be evaluated hierarchically at an alpha of 0.05 for each comparison.
  • All cause mortality [ Time Frame: We anticipate that patients will be in the study for up to 5 years. ]
    "All cause mortality" is defined in the protocol as "death from any cause". The secondary outcome measures will be analyzed the same as outlined above for the primary outcome measures. The secondary outcomes will be analyzed for the ITT population. If the primary endpoint objective is met, the secondary outcomes will be evaluated hierarchically at an alpha of 0.05 for each comparison.
Current Other Pre-specified Outcome Measures
 (submitted: July 8, 2021)
  • Emergent/Elective Coronary Revascularization [ Time Frame: From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure ]
    Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed).
  • Hospitalization for Unstable Angina [ Time Frame: From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure ]
    Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed).
  • Non-fatal Myocardial Infarction [ Time Frame: From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure ]
    Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed).
  • Non-fatal Stroke [ Time Frame: From the date of randomization and up to completion of the end-of-treatment visit (Month 60) or at study closure ]
    Participants with no observed events are censored at the earliest of withdrawal of consent date and last study contact (defined as the latest of the dates of assessments contributing to an opportunity to assess as to whether the participant has had every component of the endpoint being analyzed).
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Outcomes Study to Assess STatin Residual Risk Reduction With EpaNova in HiGh CV Risk PatienTs With Hypertriglyceridemia
Official Title  ICMJE A Long-Term Outcomes Study to Assess STatin Residual Risk Reduction With EpaNova in HiGh Cardiovascular Risk PatienTs With Hypertriglyceridemia (STRENGTH)
Brief Summary The study is a randomized, double-blind, placebo-controlled (corn oil), parallel group design that will enroll approximately 13,000 patients with hypertriglyceridemia and low HDL and high risk for CVD to be randomized 1:1 to either corn oil + statin or Epanova + statin, once daily, for approximately 3-5 years as determined when the number of MACE outcomes is reached.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Eligible Men or Women Considered High Risk for Atherosclerotic Cardiovascular Disease (CVD)
Intervention  ICMJE
  • Drug: Epanova® (omega-3 carboxylic acids)
    Adjunct to statin therapy and diet in high risk adult patients for the prevention and reduction of major adverse cardiovascular events (MACE)
    Other Name: omega-3 carboxylic acids
  • Drug: corn oil control
    corn oil control arm
Study Arms  ICMJE
  • Experimental: EPANOVA
    Epanova + statin, once daily
    Intervention: Drug: Epanova® (omega-3 carboxylic acids)
  • Active Comparator: Corn oil
    Corn oil + Statin
    Intervention: Drug: corn oil control
Publications *

*   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: July 8, 2021)
13078
Original Estimated Enrollment  ICMJE
 (submitted: April 2, 2014)
28890
Actual Study Completion Date  ICMJE May 27, 2020
Actual Primary Completion Date May 27, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Men or women, ≥18 years of age.
  2. Patient must be on a stable diet and statin* therapy at least 4 weeks prior to randomization (Visit 2) and meet the following criteria:

    1. LDL-C <100 mg/dL
    2. TG level ≥180 and <500 mg/dL and HDL-C <42 mg/dL for men or HDL-C <47 mg/dL for women
  3. Patient is at high risk for a future cardiovascular event if at least one of the following criteria (3a, 3b or 3c)* is present via patient history, physical exam, or medical records at the time of screening:

    1. Any atherosclerotic CVD as defined in protocol.
    2. History of diabetes mellitus (type 1 or 2) and ≥40 years of age for men and ≥50 years of age for women, plus one of the risk factors defined in protocol.
    3. Male patients >50 years of age or females >60 years of age, with at least one of the risk factors defined in protocol.

Key Exclusion Criteria:

1. Allergy or intolerance to omega-3 carboxylic acids, omega-3 fatty acids, omega-3-acid ethyl esters, or corn oil. 2.Use of fibrates, bile acid sequestrants, or niacin or its analogues (>250 mg/day) within 4 weeks prior to Visit 2. 3.Statin naïve at Visit 1.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   China,   Czechia,   Denmark,   Estonia,   Hungary,   Italy,   Japan,   Korea, Republic of,   Lithuania,   Mexico,   Netherlands,   New Zealand,   Poland,   Russian Federation,   South Africa,   Taiwan,   Ukraine,   United Kingdom,   United States
Removed Location Countries Argentina,   Brazil,   Czech Republic,   Latvia
 
Administrative Information
NCT Number  ICMJE NCT02104817
Other Study ID Numbers  ICMJE D5881C00004
2014-001069-28 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE
  • The Cleveland Clinic
  • IQVIA RDS Inc.
Investigators  ICMJE
Principal Investigator: Steven Nissen, MD The Cleveland Clinic
Principal Investigator: Michael Lincoff, MD The Cleveland Clinic
Principal Investigator: Stephen Nicholls, MD MonashHeart
PRS Account AstraZeneca
Verification Date August 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP