Specified Drug-use Survey of the Granular Capsule Formulation of Omega-3 Fatty Acid Ethyl Esters: OCEAN3

Specified Drug-use Survey of Lotriga Granular Capsules: OCEAN3 (Outcome Prevention on Cardiovascular Events by Antihyperlipidemic Therapy With N3-fatty Acid in Japan)

The purpose of this survey is to determine the incidence rate of cardiovascular (CV) events associated with long-term treatment with and without omega-3 fatty acid ethyl esters (Lotriga Granular Capsules) in high-risk hyperlipidemic patients treated by statin in daily medical practice.

Study Overview

• Status: Completed
• Conditions: Hyperlipidemia
• Intervention / Treatment: Drug: Omega-3 fatty acid ethyl esters; Drug: Standard antihyperlipidemic therapy other than administration of omega-3 fatty acid ethyl esters (Lotriga).

Detailed Description

This survey is planned to determine the incidence rate of cardiovascular (CV) events associated with long-term treatment with omega-3 fatty acid ethyl esters (Lotriga Granular Capsules) in high-risk hyperlipidemic patients treated by statin in daily medical practice.

The incidence rate of CV events in the participants who are treated by the standard anti-hyperlipidemic therapies other than omega-3 fatty acid ethyl esters is investigated in this survey so as to compare the events rates between two participant groups just for information.

For adults, 2 g of omega-3 fatty acid ethyl esters is usually administered orally once daily immediately after meals. However, the dose can be increased up to twice daily (to a dose of 2 g) depending on participant's triglyceride (TG) level.

• Study Type: Observational
• Enrollment (Actual): 15330

Contacts and Locations

Study Locations

• Japan
  • Osaka, Japan
  • Tokyo, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 46 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Hyperlipidemia

Description

Inclusion Criteria:

Participants who meet all of the following criteria will be included in the survey:

1. Patients with hyperlipidemia on statin therapy
2. Outpatients
3. Male participants aged ≥ 50 years and female participants aged ≥ 60 years
4. Participants with fasting TG level ≥ 150 mg/dL (within 3 months prior to the start of the observation period)

5. Participants who have at least two of the following risk factors:

   • Hypertension
   • Type 2 diabetes mellitus
   • Chronic kidney disease
   • Prior history of myocardial infarction or angina pectoris
   • Prior history of cerebral infarction
   • Peripheral arterial disease

Exclusion Criteria:

-Participants who meet any of the following criteria will be excluded from the survey:

1. Participants who have experienced coronary artery disease within 1 month prior to the start of the observation period
2. Participants who have experienced cerebrovascular disease within 1 month prior to the start of the observation period
3. Participants who have undergone heart surgery or revascularization surgery (including coronary artery intervention and peripheral arterial intervention) within 1 month prior to the start of the observation period
4. Participants who plan to undergo heart surgery or revascularization surgery (including coronary artery intervention and peripheral arterial intervention)
5. Patients with malignant tumors currently under treatment
6. Participants who have received eicosapentaenoic acid (hereinafter, EPA) products within 1 month prior to the start of the observation period, or participants who plan to receive treatment with EPA products after the start of the observation period
7. Patients with hemorrhage (e.g., hemophilia, capillary fragility, gastrointestinal ulcer, urinary tract hemorrhage, hemoptysis, or vitreous hemorrhage)
8. Participants with prior history of hypersensitivity to any ingredients in omega-3 fatty acid ethyl esters (omega-3 fatty acid ethyl esters-treated participants only)
9. Participants with prior history of treatment with omega-3 fatty acid ethyl esters

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Ever User of Omega-3 fatty acid ethyl esters 2 g; The usual adult dosage for oral use was 2 g of omega-3 fatty acid ethyl esters administered once daily or twice daily immediately after meals for treatment of hyperlipidemia. Participants received both interventions and standard antihyperlipidemic therapy as part of routine medical care.	Drug: Omega-3 fatty acid ethyl esters; Omega-3 fatty acid ethyl esters granular capsules; Other Names: Lotriga granular capsules
Never User of Omega-3 fatty acid ethyl esters 2 g; Participants received standard antihyperlipidemic therapy without omega-3 fatty acid ethyl esters 2 g as part of routine medical care.	Drug: Standard antihyperlipidemic therapy other than administration of omega-3 fatty acid ethyl esters (Lotriga).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants (Cumulative Incidence) With Specified Cardiovascular Events in Population of Omega-3 Fatty Acid Ethyl Esters 2 g User	Reported data was percentage of participants (cumulative incidence) with specified cardiovascular events from start of observation in population of omega-3 fatty acid ethyl esters 2 g user. Specified cardiovascular events were fatal and non-fatal, and defined as major adverse cardiovascular events (cardiovascular death [including sudden death, fatal myocardial infarction, fatal cardiac failure, fatal stroke {cerebral infarction, cerebral hemorrhage, and subarachnoid hemorrhage} and other cardiovascular death], non-fatal myocardial infarction, and non-fatal stroke [cerebral infarction, cerebral hemorrhage, and subarachnoid hemorrhage]), angina pectoris requiring coronary revascularization (i.e., percutaneous transluminal coronary angioplasty [PCI] or coronary artery bypass grafting [CABG]), peripheral arterial disease requiring surgery or peripheral arterial intervention.	Up to 36 months
Percentage of Participants (Cumulative Incidence) With Specified Cardiovascular in Population of Omega-3 Fatty Acid Ethyl Esters 2 g Never User	Reported data was percentage of participants (cumulative incidence) with specified cardiovascular events from start of observation in population of omega-3 fatty acid ethyl esters 2 g never user. Specified cardiovascular events were fatal and non-fatal, and defined as major adverse cardiovascular events (cardiovascular death [including sudden death, fatal myocardial infarction, fatal cardiac failure, fatal stroke {cerebral infarction, cerebral hemorrhage, and subarachnoid hemorrhage} and other cardiovascular death], non-fatal myocardial infarction, and non-fatal stroke [cerebral infarction, cerebral hemorrhage, and subarachnoid hemorrhage]), angina pectoris requiring coronary revascularization (i.e., percutaneous transluminal coronary angioplasty [PCI] or coronary artery bypass grafting [CABG]), peripheral arterial disease requiring surgery or peripheral arterial intervention.	Up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants (Cumulative Incidence) With Death From All Causes (Cardiovascular and Non-cardiovascular Deaths) in Population of Omega-3 Fatty Acid Ethyl Esters 2 g User	Reported data was percentage of participants (cumulative incidence) with death from all causes (cardiovascular and non-cardiovascular deaths) from start of observation in population of omega-3 fatty acid ethyl esters 2 g user.	Up to 36 months
Percentage of Participants (Cumulative Incidence) With Death From All Causes (Cardiovascular and Non-cardiovascular Deaths) in Population of Omega-3 Fatty Acid Ethyl Esters 2 g Never User	Reported data was percentage of participants (cumulative incidence) with death from all causes (cardiovascular and non-cardiovascular deaths) from start of observation in population of omega-3 fatty acid ethyl esters 2 g never user.	Up to 36 months
Percentage of Participants (Cumulative Incidence) With Major Adverse Cardiovascular Events (MACE) in Population of Omega-3 Fatty Acid Ethyl Esters 2 g User	Reported data was percentage of participants (cumulative incidence) with major adverse cardiovascular events (MACE) from start of observation in population of omega-3 fatty acid ethyl esters 2 g user. MACE included cardiovascular death (including sudden death, fatal myocardial infarction, fatal cardiac failure, fatal stroke [cerebral infarction, cerebral hemorrhage, and subarachnoid hemorrhage] and other cardiovascular death), non-fatal myocardial infarction, and non-fatal stroke (cerebral infarction, cerebral hemorrhage, and subarachnoid hemorrhage).	Up to 36 months
Percentage of Participants (Cumulative Incidence) With Major Adverse Cardiovascular Events (MACE) in Population of Omega-3 Fatty Acid Ethyl Esters 2 g Never User	Reported data was percentage of participants (cumulative incidence) with major adverse cardiovascular events (MACE) from start of observation in population of omega-3 fatty acid ethyl esters 2 g never user. MACE included cardiovascular death (including sudden death, fatal myocardial infarction, fatal cardiac failure, fatal stroke [cerebral infarction, cerebral hemorrhage, and subarachnoid hemorrhage] and other cardiovascular death), non-fatal myocardial infarction, and non-fatal stroke (cerebral infarction, cerebral hemorrhage, and subarachnoid hemorrhage).	Up to 36 months
Percentage of Participants (Cumulative Incidence) With All Cardiovascular Events From in Population of Omega-3 Fatty Acid Ethyl Esters 2 g User	Reported data was percentage of participants (cumulative incidence) with all cardiovascular events from start of observation in population of omega-3 fatty acid ethyl esters 2 g user. All cardiovascular events included MACE, angina pectoris requiring hospitalization, angina pectoris requiring coronary revascularization (i.e., PCI or CABG), cardiac failure requiring hospitalization, transient ischaemic attack requiring hospitalization, peripheral arterial disease requiring hospitalization, peripheral arterial disease requiring surgery or peripheral arterial intervention.	Up to 36 months
Percentage of Participants (Cumulative Incidence) With All Cardiovascular Events in Population of Omega-3 Fatty Acid Ethyl Esters 2 g Never User	Reported data was percentage of participants (cumulative incidence) with all cardiovascular events from start of observation in population of omega-3 fatty acid ethyl esters 2 g never user. All cardiovascular events included MACE, angina pectoris requiring hospitalization, angina pectoris requiring coronary revascularization (i.e., PCI or CABG), cardiac failure requiring hospitalization, transient ischaemic attack requiring hospitalization, peripheral arterial disease requiring hospitalization, peripheral arterial disease requiring surgery or peripheral arterial intervention.	Up to 36 months
Percentage of Participants (Cumulative Incidence) With Individual Cardiovascular Events (Cardiovascular Death) in Population of Omega-3 Fatty Acid Ethyl Esters 2 g User	Reported data was percentage of participants (cumulative incidence) with individual cardiovascular events (cardiovascular death) from start of observation in population of omega-3 fatty acid ethyl esters 2 g user.	Up to 36 months
Percentage of Participants (Cumulative Incidence) With Individual Cardiovascular Events (Cardiovascular Death) in Population of Omega-3 Fatty Acid Ethyl Esters 2 g Never User	Reported data was percentage of participants (cumulative incidence) with individual cardiovascular events (cardiovascular death) from start of observation in population of omega-3 fatty acid ethyl esters 2 g never user.	Up to 36 months
Percentage of Participants (Cumulative Incidence) With Individual Cardiovascular Events (Non-fatal Myocardial Infarction) in Population of Omega-3 Fatty Acid Ethyl Esters 2 g User	Reported data was percentage of participants (cumulative incidence) with individual cardiovascular events (non-fatal myocardial infarction) from start of observation in population of omega-3 fatty acid ethyl esters 2 g user.	Up to 36 months
Percentage of Participants (Cumulative Incidence) With Individual Cardiovascular Events (Non-fatal Myocardial Infarction) in Population of Omega-3 Fatty Acid Ethyl Esters 2 g Never User	Reported data was percentage of participants (cumulative incidence) with individual cardiovascular events (non-fatal myocardial infarction) from start of observation in population of omega-3 fatty acid ethyl esters 2 g never user.	Up to 36 months
Percentage of Participants (Cumulative Incidence) With Individual Cardiovascular Events (Non-fatal Stroke) in Population of Omega-3 Fatty Acid Ethyl Esters 2 g User	Reported data was percentage of participants (cumulative incidence) with individual cardiovascular events (non-fatal stroke) from start of observation in population of omega-3 fatty acid ethyl esters 2 g user.	Up to 36 months
Percentage of Participants (Cumulative Incidence) With Individual Cardiovascular Events (Non-fatal Stroke) in Population of Omega-3 Fatty Acid Ethyl Esters 2 g Never User	Reported data was percentage of participants (cumulative incidence) with individual cardiovascular events (non-fatal stroke) from start of observation in population of omega-3 fatty acid ethyl esters 2 g never user.	Up to 36 months
Percentage of Participants (Cumulative Incidence) With Individual Cardiovascular Events (Angina Pectoris Requiring Hospitalization) in Population of Omega-3 Fatty Acid Ethyl Esters 2 g User	Reported data was percentage of participants (cumulative incidence) with individual cardiovascular events (angina pectoris requiring hospitalization) from start of observation in population of omega-3 fatty acid ethyl esters 2 g user.	Up to 36 months
Percentage of Participants (Cumulative Incidence) With Individual Cardiovascular Events (Angina Pectoris Requiring Hospitalization) in Population of Omega-3 Fatty Acid Ethyl Esters 2 g Never User	Reported data was percentage of participants (cumulative incidence) with individual cardiovascular events (angina pectoris requiring hospitalization) from start of observation in population of omega-3 fatty acid ethyl esters 2 g never user.	Up to 36 months
Percentage of Participants (Cumulative Incidence) With Individual Cardiovascular Events (Angina Pectoris Requiring Coronary Revascularization) in Population of Omega-3 Fatty Acid Ethyl Esters 2 g User	Reported data waspercentage of participants (cumulative incidence) with individual cardiovascular events (angina pectoris requiring coronary revascularization ) from start of observation in population of omega-3 fatty acid ethyl esters 2 g user.	Up to 36 months
Percentage of Participants (Cumulative Incidence) With Individual Cardiovascular Events (Angina Pectoris Requiring Coronary Revascularization) in Population of Omega-3 Fatty Acid Ethyl Esters 2 g Never User	Reported data was percentage of participants (cumulative incidence) with individual cardiovascular events (angina pectoris requiring coronary revascularization) from start of observation in population of omega-3 fatty acid ethyl esters 2 g never user.	Up to 36 months
Percentage of Participants (Cumulative Incidence) With Individual Cardiovascular Events (Cardiac Failure Requiring Hospitalization) in Population of Omega-3 Fatty Acid Ethyl Esters 2 g User	Reported data was percentage of participants (cumulative incidence) with individual cardiovascular events (cardiac failure requiring hospitalization) from start of observation in population of omega-3 fatty acid ethyl esters 2 g user.	Up to 36 months
Percentage of Participants (Cumulative Incidence) With Individual Cardiovascular Events (Cardiac Failure Requiring Hospitalization) in Population of Omega-3 Fatty Acid Ethyl Esters 2 g Never User	Reported data was percentage of participants (cumulative incidence) with individual cardiovascular events (cardiac failure requiring hospitalization) from start of observation in population of omega-3 fatty acid ethyl esters 2 g never user.	Up to 36 months
Percentage of Participants (Cumulative Incidence) With Individual Cardiovascular Events (Transient Ischaemic Attack Requiring Hospitalization) in Population of Omega-3 Fatty Acid Ethyl Esters 2 g User	Reported data was percentage of participants (cumulative incidence) with individual cardiovascular events (transient ischaemic attack requiring hospitalization) from start of observation in population of omega-3 fatty acid ethyl esters 2 g user.	Up to 36 months
Percentage of Participants (Cumulative Incidence) With Individual Cardiovascular Events (Transient Ischaemic Attack Requiring Hospitalization) in Population of Omega-3 Fatty Acid Ethyl Esters 2 g Never User	Reported data was percentage of participants (cumulative incidence) with individual cardiovascular events (transient ischaemic attack requiring hospitalization) from start of observation in population of omega-3 fatty acid ethyl esters 2 g never user.	Up to 36 months
Percentage of Participants (Cumulative Incidence) With Individual Cardiovascular Events (Peripheral Arterial Disease Requiring Hospitalization) in Population of Omega-3 Fatty Acid Ethyl Esters 2 g User	Reported data was percentage of participants (cumulative incidence) with individual cardiovascular events (peripheral arterial disease requiring hospitalization) from start of observation in population of omega-3 fatty acid ethyl esters 2 g user.	Up to 36 months
Percentage of Participants (Cumulative Incidence) With Individual Cardiovascular Events (Peripheral Arterial Disease Requiring Hospitalization) in Population of Omega-3 Fatty Acid Ethyl Esters 2 g Never User	Reported data was percentage of participants (cumulative incidence) with individual cardiovascular events (peripheral arterial disease requiring hospitalization) from start of observation in population of omega-3 fatty acid ethyl esters 2 g never user.	Up to 36 months
Percentage of Participants (Cumulative Incidence) With Individual Cardiovascular Events (Peripheral Arterial Disease Requiring Surgery or Peripheral Arterial Intervention) in Population of Omega-3 Fatty Acid Ethyl Esters 2 g User	Reported data was percentage of participants (cumulative incidence) with individual cardiovascular events (peripheral arterial disease requiring surgery or peripheral arterial intervention) from start of observation in population of omega-3 fatty acid ethyl esters 2 g user.	Up to 36 months fatty
Percentage of Participants (Cumulative Incidence) With Individual Cardiovascular Events (Peripheral Arterial Disease Requiring Surgery or Peripheral Arterial Intervention) in Population of Omega-3 Fatty Acid Ethyl Esters 2 g Never User	Reported data was percentage of participants (cumulative incidence) with individual cardiovascular events (peripheral arterial disease requiring surgery or peripheral arterial intervention) from start of observation in population of omega-3 fatty acid ethyl esters 2 g never user.	Up to 36 months

Collaborators and Investigators

• Sponsor: Takeda

Publications and helpful links

General Publications

• Teramoto T, Ogawa H, Ueshima H, Okada Y, Haze K, Matsui S, Fujikawa K, Hashimoto T, Sakui S, Nishimura K, Kajita M, Horimoto A, Fernandez J. Effect of omega-3 fatty acids on cardiovascular events in high-risk patients with hypertriglyceridemia in Japan: a 3-year post-marketing surveillance study (OCEAN3 survey). Expert Opin Drug Saf. 2022 Jun 30. doi: 10.1080/14740338.2022.2094914. Online ahead of print.

Helpful Links

• To obtain more information on the study, click here/on this link

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2014
• Primary Completion (Actual): July 14, 2020
• Study Completion (Actual): July 14, 2020

Study Registration Dates

• First Submitted: November 4, 2014
• First Submitted That Met QC Criteria: November 4, 2014
• First Posted (Estimate): November 6, 2014

Study Record Updates

• Last Update Posted (Actual): February 18, 2022
• Last Update Submitted That Met QC Criteria: December 2, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Pharmacological therapy
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Hyperlipidemias; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Lipid Regulating Agents; Hypolipidemic Agents
• Other Study ID Numbers: 142-012; JapicCTI-142680 (Registry Identifier: JapicCTI)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No