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

NCT06720662 | Not Yet Recruiting DMC

• 1 other identifier: 77740424.3.3001.0068
• Study Type: interventional
• Target: 294
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Atherosclerosis Cardiovascular Disease

Keywords

omega 3 fatty acids; atherosclerosis; oxylipins

Outcome Measures

Primary Outcomes (1)

• Eicosapent ethyl ester (IPE) and high sensitivity C-Reactive Protein (hs-CRP)

  Eicosapent ethyl ester (IPE) combined with a classical pharmacological treatment, will contribute to reduce high sensitivity C-Reactive Protein (hs-CRP) in patients undergoing secondary prevention for cardiovascular disease. the concentration hsCRP was chosen based on the fact that it is the only inflammatory marker mentioned in the Prevention Guidelines (Arnett et al., 2019), was selected in the "Cantos" study (Ridker et al., 2018), has shown correlation with IPE in the "REDUCE-IT" study (Bhatt et al., 2019) and also having observed a reduction in patients supplemented with fish oil in other studies (Scolaro et al., 2018; Elisia et al., 2022).

  From enrollment to the end of treatment at 6 weeks

Study Arms (2)

IPE Supplementation Group

ACTIVE COMPARATOR

Dietary Supplement: Icosapent Ethy capsules

Dietary Supplement: Icosapent-ethyl ester capsules

Placebo Group

PLACEBO COMPARATOR

Dietary Supplement: Corn oil Control

Dietary Supplement: Corn oil Control

Interventions

Icosapent-ethyl ester capsules DIETARY_SUPPLEMENT

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

IPE Supplementation Group

Corn oil Control DIETARY_SUPPLEMENT

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

Placebo Group

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Patients with Atrial fibrillation and Bleeding related disorders.

Sponsors & Collaborators

• University of Sao Paulo: lead
• InCor Heart Institute: collaborator

Related Publications (3)

• 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.

  PMID: 35281761 BACKGROUND

• 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.

  PMID: 33476944 BACKGROUND

• 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.

  PMID: 30415628 BACKGROUND

MeSH Terms

Conditions

Atherosclerosis

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Central Study Contacts

Inar Castro Inar Castro Erger, Professor

CONTACT

+55(11)97429-3369; inar@usp.br

Vivian Moura Doctor Student, Master

CONTACT

+55(11)96645-2370; vivianmoura@usp.br

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 2, 2024
• First Posted: December 6, 2024
• Study Start: April 1, 2025
• Primary Completion: December 30, 2025
• Study Completion: January 30, 2026
• Last Updated: December 13, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share