A Long-Term Outcomes Study to Assess STatin Residual Risk Reduction with EpaNova in HiGh Cardiovascular Risk PatienTs with Hypertriglyceridemia (STRENGTH)
- Conditions
- Severe persistent Hypertriglyceridemia in High Cardiovascular RiskPatientsMedDRA version: 17.1Level: LLTClassification code 10020870Term: HypertriglyceridemiaSystem Organ Class: 100000004861Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2014-001069-28-IT
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 13000
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 where the qualifying lipid parameters should be obtained from the same visit:
a. LDL-C <100 mg/dL (<2.59 mmol/L). Patient will also qualify if LDL-C =100 mg/dL (=2.59 mmol/L) and if on a high-intensity or maximum tolerated moderate- or lowintensity statin dose, with or without ezetimibe therapy, for at least 4 weeks (see Appendix D). The maximum tolerated dosage of a statin is defined as the approved dose
per local label that the patient can tolerate without unacceptable adverse effects such as muscle aches/pain/weakness or elevations in liver enzymes or creatine kinase (CK) that are determined by the investigator to be clinically relevant and due to statin therapy.
b. TG level =200 and <500 mg/dL (=2.26 and <5.65 mmol/L) and HDL-C <40 mg/dL (1.03 mmol/L) for men or HDL-C <45 mg/dL (1.16 mmol/L) for women. *co-administration with ezetimibe or fixed-dose ezetimibe/simvastatin 10/10, 10/20, 10/40 mg (see restrictions regarding 80 mg simvastatin in Section 7.4) or fixed-dose
ezetimibe/atorvastatin 10/10, 10/20, 10/40, or 10/80 mg is allowed.
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:
a. Any atherosclerotic CVD as defined by one or more of the following:
- previous clinical myocardial infarction (MI) =30 days prior to randomization
- percutaneous coronary intervention (PCI) including balloon angioplasty and coronary stenting = 6 months prior to randomization
- coronary artery bypass grafting (CABG) =30 days prior to randomization
- coronary angiogram including computed tomography angiogram (CTA) demonstrating more than or equal to a 50% stenosis in at least one native or graft vessel
- anginal symptoms with a defect documented by stress testing with nuclear perfusion imaging or a wall motion abnormality determined by stress echocardiogram
- asymptomatic coronary ischemia documented by stress testing with nuclear perfusion imaging or by stress echocardiogram
- peripheral vascular disease with symptoms of claudication and ankle brachial index <0.9 performed by a vascular lab or angiogram (including CTA) showing more than or equal to 50% stenosis)
- history of peripheral arterial revascularization (surgical or percutaneous) =30 days prior to randomization
- carotid endarterectomy or more than or equal to 50% stenosis in a carotid artery determined by carotid ultrasound or angiogram =30 days prior to randomization
- history of abdominal aortic aneurysm diagnosed =30 days prior to randomization
- ischemic stroke =30 days prior to randomization
b. 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 following risk factors:
- chronic cigarette smoking at screening (at least 1 cigarette per day for > 1 month)
- history of hypertension (blood pressure >140/90 mm Hg) or taking antihypertensive medication
- high-sensitivity C-reactive protein (hs-CRP) > 2.0 mg/L (19.05 nmol/L) determined at Visit 1
- history of albuminuria (urinary albumin:creatinine ratio [ACR] >30 mg/g).
c. Male patients >50 years of age or females >60 years of age, with at least one of the following risk factors:
- family history of premature coronary hear
1. Allergy or intolerance to omega-3 carboxylic acids, omega-3 fatty acids, omega-3-acid ethyl esters, or corn oil.
2. Known hypersensitivity to fish and/or shellfish.
3. Use of fibrates, bile acid sequestrants, or niacin or its analogues (>250 mg/day) within 4 weeks prior to Visit 2. Patients taking these agents may be considered for inclusion in the study if these therapies have been discontinued for 4 weeks or more prior to Visit 2.
4. Statin naïve at Visit 1.
5. Use of simvastatin 80 mg or ezetimibe/simvastatin 10/80 mg within 4 weeks prior to Visit 2. Patients taking these agents may be considered for inclusion in the study if these therapies have been discontinued and replaced with a protocol acceptable statin treatment that is stabilized for 4 weeks or more prior to Visit 2.
6. Use of any prescription medications containing eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA), e.g. Lovaza® or Vascepa®, within 4 weeks prior to Visit 2. Patients taking these agents may be considered for inclusion in the study if these therapies have been discontinued for 4 weeks or more prior to Visit 2.
7. More than one capsule/day (any dose) of omega-3 dietary supplements. Up to one capsule/day will be permitted if started prior to Visit 1 (new omega-3 supplements are not permitted at Visits 1, 1a, or 1b,
8. Use of prescription or over-the-counter (OTC) weight loss drugs at any time after Visit 1.
9. Chronic use of oral corticosteroids during screening (acute use for inflammation for example from poison ivy, or intranasal or inhaled steroids for allergies/asthma, or intraarticular injections are allowed).
10. Use of tamoxifen, estrogens, progestins, or testosterone, that has not been stable for >4 weeks at Visit 1, or is unstable prior to Visit 2.
11. Known lipoprotein lipase impairment or deficiency, or apolipoprotein C-II deficiency.
12. Hemoglobin A1c (Hb A1c) >10% at Visit 1.
13. Poorly controlled hypertension (resting blood pressure =180 mm Hg systolic and/or =100 mm Hg diastolic) at two consecutive visits prior to randomization at Visit 2.
14. Uncontrolled hypothyroidism, or thyroid stimulating hormone (TSH) >2.0 times upper limit of normal (ULN) at Visit 1. Patients who are clinically euthyroid, on stable thyroid replacement therapy for 2 months prior to Visit 1 are allowed.
15. History of cancer (except non-melanoma skin cancer, or carcinoma in situ of cervix) within the previous two years.
16. Patients on dialysis.
17. Females who are pregnant, planning to be pregnant during the study period, lactating, or women of childbearing potential who are not using an acceptable method of contraception. A woman is considered of childbearing potential if she is not surgically sterile or if her last menstrual period was <12 months prior to Visit 1. Acceptable methods of contraception for this study include use of double barrier contraception, intrauterine device, all oral, patch, etc. hormonal contraceptives as long as dose and type is stable for 3 months prior to Visit 1. In addition, true abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject.
18. Creatine kinase >5.0 times ULN; aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3.0 times ULN; or total bilirubin (TBL) >2.0 times ULN (except with a confirmed diagnosis of Gilbert’s disease), at Visit 1. A diagnosis of non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) with stable
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method