Effect of Icosapent-ethyl Ester (IPE) to Reduce the Residual Risk Cardiovascular Disease.

NCT ID: NCT06720662

Last Updated: 2024-12-13

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 294 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-01
• Study Completion Date: 2026-01-30

Brief Summary

Cardiovascular diseases (CVDs) are the leading cause of global mortality, despite significant advances in prevention and treatment. Atherosclerosis, a chronic inflammatory condition, underlies ischemic events such as infarction and stroke, triggered by the instability and rupture of plaques. Current guidelines recommend drugs primarily aimed at reducing Low-Density-Lipoprotein cholesterol (LDL-C), arterial pressure, and glucose levels for atherosclerosis patients. However, there is little option of approved medications specifically targeting inflammation within the arterial plaques. Consequently, a significant proportion of patients face residual risks. On the contrary, numerous studies have highlighted the anti-inflammatory effects provided by omega-3 fatty acids (n-3 FA), specially the eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and their derived oxylipins. These molecules exhibit the ability to enhance the phenotype of macrophages, increasing their capacity for efferocytosis, thereby improving plaque stability. Icosapent ethyl (IPE) is an esterifed version of eicosapentaenoic acid (EPA) and acts as a prodrug in the body to exert its effects. Icosapent ethyl (IPE) was the first fish oil product approved by the US Food and Drug Administration (FDA) to reduce the risk of atherosclerotic cardiovascular disease (ASCVD) in adults. Hence, the hypothesis of this study is that supplementing patients with IPE, in addition to their standard clinical treatment, will enhance macrophage functionality, thereby reducing inflammatory and oxidative stress biomarkers in comparison to a placebo. To test this hypothesis,a Randomized, Double-blind, Placebo-controlled Clinical trial will be performed, in which 294 patients under secondary prevention for CVDs will receive a 6-month supplementation of purified eicosapentaenoic acid-icosapent ethyl (4.0 g) daily or a Placebo (corn oil). Blood samples and anthropometric measurements will be taken at the beginning and end of the period. Basic clinical markers will be assessed, and monocytes will be collected and characterized. Fatty acid profiles and oxylipins will be determined through chromatography coupled with mass spectrometry. Finally, changes in biomarkers for both groups will undergo multivariate analysis to identify characteristics associated with the response to supplementation. Data from this study aims to provide support for physicians considering the prescription of bioactive compounds as a complementary therapy for atherosclerosis, with the goal of reducing residual risks and subsequently decreasing mortality resulting from cardiovascular events.

Detailed Description

A Randomized, Double-blind, Parallel, Placebo-controlled Clinical trial will be carried out. Initially, subjects will be randomly assigned to receive the supplementation or placebo treatment for 6 months. Daily supplemental treatment (IPE) will consist of Icosapent Ethy capsules (4.0 g of EPA) taken twice a day (2.0 g/day x 2). Placebo treatment (PLACEBO) will consist of similar capsules containing corn oil instead of IPE. It has been argued that the CV benefit with IPE in certain trials (most notably REDUCEIT) related to the use of pharmaceutical grade mineral oil as comparator (Sherratt et al., 2023). Although a comprehensive review of mineral oil use in CV trials found no reproducible, consistently statistically significant effect of mineral oil on inflammatory markers, including hsCRP (Olshansky et al., 2020), the investigators opted for use of corn oil as placebo, while there is no consensus about this subject. Participants will be instructed to consume half capsules after lunch and half after dinner. During the trial, the subjects will maintain their habitual routine and diet. Prescribed drugs will be kept without any change throughout the study. The Icosapent-ethyl (IPE) will be purchased from BASF S.A., Avenida Nacoes Unidas, 14171, 04794-000 Sao Paulo, Brazil, and the oil will be encapsulated in a Brazilian company still not defined.

Conditions

Atherosclerosis Cardiovascular Disease

Keywords

omega 3 fatty acids; atherosclerosis; oxylipins

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

IPE Supplementation Group

Dietary Supplement: Icosapent Ethy capsules

Group Type: ACTIVE_COMPARATOR

Icosapent-ethyl ester capsules

Intervention Type: DIETARY_SUPPLEMENT

Icosapent-ethyl ester (4.0 g of EPA) taken twice a day (2.0 g/day x 2) for six months.

Placebo Group

Dietary Supplement: Corn oil Control

Group Type: PLACEBO_COMPARATOR

Corn oil Control

Intervention Type: DIETARY_SUPPLEMENT

Corn oil twice a day (2.0 g/day x 2) for six months.

Interventions

Icosapent-ethyl ester capsules

Icosapent-ethyl ester (4.0 g of EPA) taken twice a day (2.0 g/day x 2) for six months.

Intervention Type: DIETARY_SUPPLEMENT

Corn oil Control

Corn oil twice a day (2.0 g/day x 2) for six months.

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

hsCRP level - mg/liter: from 1 to 4.5; Triglyceride level - mg/dl: from 150 - 500; HDL cholesterol level - mg/dl: from 30 - 50 and LDL cholesterol level - mg/dl: from 40 - 100.

Exclusion Criteria

Patients with Atrial fibrillation and Bleeding related disorders.

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• Minimum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

InCor Heart Institute

OTHER

Sponsor Role: collaborator

University of Sao Paulo

OTHER

Sponsor Role: lead

Responsible Party

Inar Castro Erger

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Inar Castro Inar Castro Erger, Professor

Role: CONTACT

Phone: +55(11)97429-3369

Email: inar@usp.br

Vivian Moura Doctor Student, Master

Role: CONTACT

Phone: +55(11)96645-2370

Email: vivianmoura@usp.br

References

Cartolano FC, Dias GD, Miyamoto S, Damasceno NRT. Omega-3 Fatty Acids Improve Functionality of High-Density Lipoprotein in Individuals With High Cardiovascular Risk: A Randomized, Parallel, Controlled and Double-Blind Clinical Trial. Front Nutr. 2022 Feb 23;8:767535. doi: 10.3389/fnut.2021.767535. eCollection 2021.

Reference Type: BACKGROUND

PMID: 35281761 (View on PubMed)

Atar D, Jukema JW, Molemans B, Taub PR, Goto S, Mach F, CerezoOlmos C, Underberg J, Keech A, Tokgozoglu L, Bonaca MP. New cardiovascular prevention guidelines: How to optimally manage dyslipidaemia and cardiovascular risk in 2021 in patients needing secondary prevention? Atherosclerosis. 2021 Feb;319:51-61. doi: 10.1016/j.atherosclerosis.2020.12.013. Epub 2021 Jan 18.

Reference Type: BACKGROUND

PMID: 33476944 (View on PubMed)

Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT Jr, Juliano RA, Jiao L, Granowitz C, Tardif JC, Ballantyne CM; REDUCE-IT Investigators. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019 Jan 3;380(1):11-22. doi: 10.1056/NEJMoa1812792. Epub 2018 Nov 10.

Reference Type: BACKGROUND

PMID: 30415628 (View on PubMed)

Other Identifiers

77740424.3.3001.0068

Identifier Type: -

Identifier Source: org_study_id