Effect of Vascepa on Improving Coronary Atherosclerosis in People With High Triglycerides Taking Statin Therapy (EVAPORATE)

• ClinicalTrials.gov Identifier: NCT02926027
• Recruitment Status: Active, not recruiting
• First Posted: October 6, 2016
• Last Update Posted: February 15, 2019
• Sponsor: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
• Collaborator: Intermountain Research and Medical Foundation
• Information provided by (Responsible Party): Matthew J. Budoff, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Study Description

Brief Summary:

Effect of Vascepa on Progression of Coronary Atherosclerosis in Persons with Elevated Triglycerides (200-499) on Statin Therapy. The study is to determine progression rates of low attenuation plaque under influence of Vascepa as compared to placebo.

Condition or disease	Intervention/treatment	Phase
Hypertriglyceridemia	Drug: Vascepa; Drug: placebo	Phase 4

Detailed Description:

Residual cardiovascular (CV) risk remains in dyslipidemic patients despite intensive statin therapy, underscoring the need for additional intervention. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, is incorporated into membrane phospholipids and atherosclerotic plaques and exerts beneficial effects on the pathophysiologic cascade from onset of plaque formation through rupture. EPA also improves atherogenic dyslipidemia characterized by reduction of triglycerides without raising low-density lipoprotein cholesterol. All of this data supports the biologic plausibility of EPA as an anti-atherosclerotic agent. The goal of this study is to evaluate whether treatment with Vascepa (4 grams) results in a greater change from baseline in low attenuation plaque than placebo in subjects with elevated triglycerides (200-499 mg/dl).

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Effect of Vascepa on Progression of Coronary Atherosclerosis in Persons With Elevated Triglycerides (200-499) on Statin Therapy
• Actual Study Start Date: September 14, 2016
• Estimated Primary Completion Date: September 2019
• Estimated Study Completion Date: September 2019

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Active subjects; Vascepa (4 gm/day), oral dose	Drug: Vascepa; Vascepa is a an Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid.
Placebo Comparator: Placebo subject; oral dose of placebo	Drug: placebo; placebo

Outcome Measures

Primary Outcome Measures :

1. Progression rates of low attenuation plaque under influence of Vascepa as compared to placebo. [ Time Frame: 18 months ]

Secondary Outcome Measures :

1. The morphology of non-calcified coronary atherosclerotic plaque (NCP) [ Time Frame: 18 months ]
2. markers of inflammation (Lp-PLA2) [ Time Frame: 18 months ]
   changes in markers of inflammation
3. changes in markers of LDL and HDL cholesterol [ Time Frame: 18 months ]
   changes in markers of cholesterol
4. The composition of non-calcified coronary atherosclerotic plaque (NCP) [ Time Frame: 18 months ]

Eligibility Criteria

• Ages Eligible for Study: 30 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Elevated triglycerides (fasting value between 200-499 mg/dl) at qualifying or baseline visit.
• LDL-C ≤115 mg/dL on appropriate statin therapy
• LDL-C >40 mg/dL
• Stable diet and exercise, as defined as the same pattern for the previous 4 weeks
• Stable treatment with a statin+/- ezetimibe for at least 4 weeks
• Patients with at least 1 angiographic stenosis with at least 20% narrowing by coronary computed tomography angiography (CTA).
• Willingness to be on birth control for women of childbearing age or established post-menopausal

Exclusion Criteria:

• A contraindication to fish or fish oils including: known hypersensitivity to drug or fish.
• Any unstable medical, psychiatric or substance abuse disorder that in the opinion of the investigator or principal investigator is likely to affect the subject's ability to complete the study or precludes the subject's participation in the study.
• Non-study lipid altering medications or supplements (ie - Niacin, PCSK9, fibrates, bile acid Sequestrants, dietary fish oil supplement capsules, orlistat [OTC (Alli®) as well as Rx (Xenical®)] or other drugs used for weight loss).
• Stable (same daily dose for the last 4 weeks) on medications that can affect lipids (retinoids, hormones, steroids, HIV medications, chemotherapy, thyroid medications).
• BMI > 40
• Bleeding disorder
• Uncontrolled hypertension (SBP≥ 180 mmHg or DBP≥100 mmHg)
• History of known myocardial infarction, stroke or life-threatening arrhythmia within the prior six months.
• NYHA Class III- IV heart failure
• History of malignancy within the last 5 years (other than skin cancer) or evidence of active cancer which would require concomitant cancer chemotherapy.
• Serum creatinine > 1.4 mg/dl
• Drug or alcohol abuse, or current intake of more than 14 ounces of alcohol per week for men and 10 ounces for women
• Concurrent enrollment in another placebo-controlled trial or within 30 days of finishing another trial
• Partial ileal bypass or known gastrointestinal disease limiting drug absorption
• History of hypertensive encephalopathy or cerebrovascular accident
• Hematological or biochemical values at screening outside the reference ranges considered as clinically significant in the opinion of the investigator or PI
• Pregnancy
• Genetic mutations/polymorphisms having an effect on blood lipids
• History of coronary artery bypass surgery
• Allergy to contrast material
• Allergy to beta-blocker in subjects with resting heart rate >70 bpm

Contacts and Locations

Locations

United States, California

Los Angeles Biomedical Research Institute

Torrance, California, United States, 90502

United States, Utah

Intermountain Medical Center, Intermountain Heart Institute

Murray, Utah, United States, 84157

Sponsors and Collaborators

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Intermountain Research and Medical Foundation

Investigators

• Principal Investigator: Matthew Budoff, MD; Los Angeles Biomedical Research Institute (LABioMed)

More Information

• Responsible Party: Matthew J. Budoff, Principal Investigator, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
• ClinicalTrials.gov Identifier: NCT02926027
• Other Study ID Numbers: 21733-01
• First Posted: October 6, 2016
• Last Update Posted: February 15, 2019
• Last Verified: February 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Data will be tabulated and analysed. Study site will not share any of the subject identifiers.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Atherosclerosis; Coronary Artery Disease; Myocardial Ischemia; Hypertriglyceridemia; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Coronary Disease; Heart Diseases; Eicosapentaenoic acid ethyl ester; Platelet Aggregation Inhibitors