Protective Effect of EPA on Cardiovascular Events - Full Text View

Sponsor:	Kobe University
Collaborator:	Mochida Pharmaceutical Company, Ltd.
Information provided by:	Kobe University
ClinicalTrials.gov Identifier:	NCT00231738

Purpose

The purpose of this study was to test the hypothesis that the long-term use of highly (＞98%) purified EPA, in addition to HMG-CoA reductase inhibitor (statin), would be more effective than statin alone in preventing cardiovascular events in Japanese patients with hypercholesterolemia.

Condition	Intervention	Phase
Myocardial Infarction, Unstable Angina Pectoris, Sudden Cardiac Death, Stroke, Peripheral Artery Disease	Drug: Eicosapentaenoic acid ethyl ester(EPADEL Capsule 300 TM)	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention
Official Title:	Effect of Eicosapentaenoic Acid (EPA) on Major Cardiovascular Events in Hypercholesterolemic Patients: the Japan EPA Lipid Intervention Study (JELIS)

Resource links provided by NLM:

MedlinePlus related topics: Angina Coronary Artery Disease Heart Attack Peripheral Arterial Disease

Drug Information available for: Docosahexaenoic acids Eicosapentaenoic acid Eicosapentaenoic acid ethyl ester

U.S. FDA Resources

Further study details as provided by Kobe University:

Primary Outcome Measures:

Major coronary events (sudden cardiac death, fatal and nonfatal myocardial infarction, unstable angina pectoris including hospitalization for ischemic episodes,events of angioplasty/ stenting or coronary artery bypass grafting)

Secondary Outcome Measures:

All-cause mortality
Stroke
Peripheral artery disease; and
Cancer

Estimated Enrollment:	18000
Study Start Date:	November 1996
Estimated Study Completion Date:	November 2004

Detailed Description:

Epidemiological studies from many countries including Finland, Italy, Japan, and The Netherlands have suggested that an increased intake of dietary fish or fish oil rich in the long-chain polyunsaturated n-3 fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is inversely related to the risk of atherothrombotic diseases, in particular coronary artery disease (CAD).

Results of many prospective observational cohort studies have found that diets rich in marine PUFAs may be protective against major cardiovascular events, including mortality from CAD, total cardiovascular death, all-cause mortality, and nonfatal myocardial infarction. To date, only a few studies have examined the effects of purified n-3 PUFA preparations in human subjects for short observation periods. The principle aim of the current study is to test the hypothesis that the long-term use of highly purified EPA(eicosapentaenoic acid: 1800mg/day), in addition to HMG-CoA reductase inhibitor, is effective in preventing cardiovascular events in Japanese patients with hypercholesterolemia.

Eligibility

Ages Eligible for Study:	40 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Eligible participants had a total cholesterol level of ≧250mg/dL(6.5m mol/L) at baseline.
Hyperlipidemic patients with serum total cholesterol of 250mg/dL or more. (Measurement of serum total cholesterol)
Serum total cholesterol should be measured twice at interval of 2-4weeks. A single measurement is acceptable if the cholesterol is measured by blood collection at fasting under strict compliance with dietary advice after withdrawal of the antihyperlipemic drug.
(Wash Out) The wash out period of 4weeks (8 weeks for probucol) is necessary in patients under treatment with antihyperlipemic drug. However, if treatment with the antihyperlipemic drug was started within 6 months of the initiation of the study, the patient can participate in the study without the washout period.

Exclusion Criteria:

Acute myocardial infarction occurring within last 6 months
Unstable angina pectoris
A history or complication of serious heart disease(severe arrhythmia, heart failure, cardiac myopathy, valvular disease, congenital disease, etc.)
Receiving cardiovascular reconstruction within last 6 months
Cerebrovascular disorders occurring within last 6 months
Complication of serious hepatic disease or renal disease
Malignant tumor
Uncontrollable diabetes
Hyperlipidemia arising from the following disease: Nephrotic syndrome, hypothyroidism, Cushing’s syndrome, secondary hyperlipidemia due to other disease
Hyperlipidemia due to some drugs such as steroid hormone
Hemorrhage(hemophilia, capillary fragility, gastrointestinal ulcer, urinary tract hemorrhage, hemoptysis, vitreous hemorrhage, etc.)
Hemorrhagic diathesis
Hypersensitivity to the study drug formulation
Patients intending to undergo surgery
Patients judged to be inappropriate by the physician in charge

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00231738

Locations

Japan
Kobe University Graduate School of Medicine Cardiovascular and Respiratory Medicine Division, Department of Internal Medicine
Kobe, Hyogo-prefecture, Japan, 650-0017

Sponsors and Collaborators

Kobe University

Mochida Pharmaceutical Company, Ltd.

Investigators

Principal Investigator:

Mitsuhiro Yokoyama, MD, PhD.

More Information

Publications:

Yokoyama M, Origasa H; JELIS Investigators. Effects of eicosapentaenoic acid on cardiovascular events in Japanese patients with hypercholesterolemia: rationale, design, and baseline characteristics of the Japan EPA Lipid Intervention Study (JELIS). Am Heart J. 2003 Oct;146(4):613-20.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ishikawa Y, Yokoyama M, Saito Y, Matsuzaki M, Origasa H, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K, Matsuzawa Y; JELIS Investigators. Preventive effects of eicosapentaenoic acid on coronary artery disease in patients with peripheral artery disease. Circ J. 2010 Jun 25;74(7):1451-7. Epub 2010 May 18.

Origasa H, Yokoyama M, Matsuzaki M, Saito Y, Matsuzawa Y; JELIS Investigators. Clinical importance of adherence to treatment with eicosapentaenoic acid by patients with hypercholesterolemia. Circ J. 2010 Feb 25;74(3):510-7. Epub 2010 Feb 9.

Oikawa S, Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K; JELIS Investigators, Japan. Suppressive effect of EPA on the incidence of coronary events in hypercholesterolemia with impaired glucose metabolism: Sub-analysis of the Japan EPA Lipid Intervention Study (JELIS). Atherosclerosis. 2009 Oct;206(2):535-9. Epub 2009 Apr 5.

Matsuzaki M, Yokoyama M, Saito Y, Origasa H, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K, Matsuzawa Y; JELIS Investigators. Incremental effects of eicosapentaenoic acid on cardiovascular events in statin-treated patients with coronary artery disease. Circ J. 2009 Jul;73(7):1283-90. Epub 2009 May 8.

Saito Y, Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K; JELIS Investigators, Japan. Effects of EPA on coronary artery disease in hypercholesterolemic patients with multiple risk factors: sub-analysis of primary prevention cases from the Japan EPA Lipid Intervention Study (JELIS). Atherosclerosis. 2008 Sep;200(1):135-40. Epub 2008 Jun 19.

Tanaka K, Ishikawa Y, Yokoyama M, Origasa H, Matsuzaki M, Saito Y, Matsuzawa Y, Sasaki J, Oikawa S, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K; JELIS Investigators, Japan. Reduction in the recurrence of stroke by eicosapentaenoic acid for hypercholesterolemic patients: subanalysis of the JELIS trial. Stroke. 2008 Jul;39(7):2052-8. Epub 2008 May 1.

Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K; Japan EPA lipid intervention study (JELIS) Investigators. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007 Mar 31;369(9567):1090-8.

ClinicalTrials.gov Identifier:	NCT00231738 History of Changes
Other Study ID Numbers:	No
Study First Received:	October 3, 2005
Last Updated:	October 3, 2005
Health Authority:	Japan: Ministry of Health, Labor and Welfare

Keywords provided by Kobe University:

Eicosapentaenoic acid
Coronary artery disease

Additional relevant MeSH terms:

Angina Pectoris
Angina, Unstable
Infarction
Myocardial Infarction
Death, Sudden, Cardiac
Death
Peripheral Arterial Disease
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms

Ischemia
Pathologic Processes
Necrosis
Heart Arrest
Death, Sudden
Atherosclerosis
Arteriosclerosis
Arterial Occlusive Diseases
Peripheral Vascular Diseases
Eicosapentaenoic acid ethyl ester
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012