Atherosclerosis Cardiovascular DiseaseNCT06720662
Effect of Icosapent-ethyl Ester (IPE) to Reduce the Residual Risk Cardiovascular Disease.
A study testing Icosapent-ethyl ester capsules in people with Atherosclerosis Cardiovascular Disease, run by University of Sao Paulo.
Trial 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. Read more about this study
- Who is it for?
- Ages 45 years and older
- Conditions the study is for
- Atherosclerosis Cardiovascular Disease
- What is being tested?
- Icosapent-ethyl ester capsules
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 294 participants
- Where
- No sites listed yet
- Study dates
- 1 Apr 2025to 30 Jan 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Inclusion Criteria: individuals from both sexes, aging 45 years or older having established CVD, without contraindications to the use of IPE, receiving a stable dose of a statin (± ezetimibe) for ≥4 weeks. Women should be not pregnant, not breastfeeding, not planning on becoming pregnant, and using an acceptable form of birth control during the study (if of child-bearing potential). Biomarkers should be:
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 severe heart failure, active severe liver disease, a glycated hemoglobin level greater than 10.0%, a planned coronary intervention or surgery, a history of acute or chronic pancreatitis, or known hypersensitivity to fish, shellfish, or ingredients of icosapent ethyl or placebo. Autoimmune disease requiring the use of immunosuppressive therapy or current use of systemic corticosteroid therapy; Active neoplasm with indication for surgery, chemotherapy or radiation in the last 12 months (patients with a history of neoplasia and who have undergone curative surgery without the need for treatment in the last 12 months will be allowed); Inflammatory bowel disease or chronic diarrhea; Clinically significant non-transient hematological abnormalities; Renal dysfunction (GFR < 30 mL/min/1.73 m² and/or serum creatinine > 2.5 mg/dL or < 220 μmol/l); Severe liver disease (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] > 3x ULN in the last 6 months); Inability to sign the free and informed consent form; Participation in another clinical trial involving an investigational agent within 90 days prior to screening; Intolerance or hypersensitivity to statin therapy; History of acute or chronic pancreatitis; Malabsorption syndrome and/or chronic diarrhea; Use of non-study drug-related, non-statin, lipid-altering medications, dietary supplements, Niacin (>200 mg/d) or fibrates (unless ≥28-day washout). Any n-3 fatty acid medications (unless ≥28-day washout). Bile acid sequestrants (unless ≥7-day washout), PCSK9 inhibitors (unless ≥90-day washout); Other medications (not indicated for lipid alteration): Tamoxifen, estrogens, progestins, thyroid hormone therapy, systemic corticosteroids (local, topical, inhalation, or nasal corticosteroids are allowed), HIV-protease inhibitors that have not been stable for ≥28 days prior to the qualifying lipid measurements (TG and LDL-C) during screening. Cyclophosphamide or systemic retinoids during the screening period (unless ≥28- day washout) and/or plans for use during the treatment/follow-up period ; HIV-positive patients even without AIDS; Requirement for peritoneal dialysis or hemodialysis for renal insufficiency or creatinine clearance 5 × ULN or elevation due to known muscle disease; Drug or alcohol abuse within the past 6 months, and inability/unwillingness to abstain from drug abuse and excessive alcohol consumption during the study; 16 Mental/psychological impairment or any other reason to expect patient difficulty in complying with the requirements of the study or understanding the goal and potential risks of participating in the study.
Patients with Atrial fibrillation and Bleeding related disorders.
-
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Effect of Icosapent-ethyl Ester (IPE) to Reduce the Residual Risk in Patients Undergoing Secondary Prevention for Cardiovascular Disease.
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.
Read the 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
- Being tested
- Icosapent-ethyl ester capsules, Corn oil Control
- Keywords
- omega 3 fatty acids, atherosclerosis, oxylipins
- Medical subject headings
- Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Icosapent-ethyl ester capsulesDietary supplement
Icosapent-ethyl ester (4.0 g of EPA) taken twice a day (2.0 g/day x 2) for six months.
Corn oil ControlDietary supplement
Corn oil twice a day (2.0 g/day x 2) for six months.
| Study group | Role | What they receive |
|---|---|---|
| IPE Supplementation Group | Active comparator | Dietary Supplement: Icosapent Ethy capsules Receives: Dietary Supplement: Icosapent-ethyl ester capsules |
| Placebo Group | Placebo comparator | Dietary Supplement: Corn oil Control Receives: Dietary Supplement: Corn oil Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: From enrollment to the end of treatment at 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2024
- Study start1 Apr 2025 (estimated)
- Primary completion30 Dec 2025 (estimated)
- Study completion30 Jan 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Atherosclerosis Cardiovascular DiseaseStudies of the same condition, open and under way.
- More trials run by University of Sao PauloThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 294 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo
- Sponsor type
- University, hospital or other
- Collaborators
- InCor Heart Institute
- Responsible party
- Principal investigator, Inar Castro Erger, University of Sao Paulo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06720662
- Sponsor's protocol ID
- 77740424.3.3001.0068
- Status last verified
- Nov 2024
- First submitted
- 2 Dec 2024
- Last updated
- 13 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35281761Atar 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.
PubMed 33476944Bhatt 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.
PubMed 30415628
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Icosapent-ethyl Ester (IPE) to Reduce the Residual Risk in Patients Undergoing Secondary Prevention for Cardiovascular Disease.
- ClinicalTrials.gov ID
- NCT06720662
- Acronym / sponsor ID
- 77740424.3.3001.0068
- Conditions
- Atherosclerosis Cardiovascular Disease
- Keywords
- omega 3 fatty acids, atherosclerosis, oxylipins
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 294 participants (estimated)
- Lead sponsor
- University of Sao PauloUniversity, hospital or other
- Collaborators
- InCor Heart Institute
- Study start
- 1 Apr 2025 (estimated)
- Primary completion
- 30 Dec 2025 (estimated)
- Study completion
- 30 Jan 2026 (estimated)
- First posted
- 6 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IPE Supplementation Group | Active comparator | Dietary Supplement: Icosapent-ethyl ester capsulesDietary Supplement: Icosapent Ethy capsules |
| Placebo Group | Placebo comparator | Dietary Supplement: Corn oil ControlDietary Supplement: Corn oil Control |
Who may qualify
- Ages
- 45 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Icosapent-ethyl ester capsulesIcosapent-ethyl ester (4.0 g of EPA) taken twice a day (2.0 g/day x 2) for six months. | Dietary supplement | IPE Supplementation Group |
| Corn oil ControlCorn oil twice a day (2.0 g/day x 2) for six months. | Dietary supplement | Placebo Group |
Primary outcome
Eicosapent ethyl ester (IPE) and high sensitivity C-Reactive Protein (hs-CRP)
Time frame: From enrollment to the end of treatment at 6 weeks
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).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2024.
- Background: PubMed 35281761Cartolano 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.
- Background: PubMed 33476944Atar 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.
- Background: PubMed 30415628Bhatt 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.
- Individual participant dataSharing planned: No
Related trials for Atherosclerosis Cardiovascular Disease
Active, not recruitingPhase 4
Effects of Sequential Therapy With Mexidol® (Intravenous) and Mexidol® FORTE 250 (Oral) on Functional Brain Activity Assessed by Functional Magnetic Resonance Imaging and Biochemical Parameters in Patients With Chronic Cerebral Ischemia: A Comparison of Patients With and Without Metabolic Disorders
Metabolic Abnormalities, Obesity & Overweight
Active, not recruiting
SUCCESS (SelUtion, Safety, effiCaCy, hEalth economicS and promS) PTA Study
Peripheral Artery Disease
Active, not recruitingPhase 3
A Study of Inclisiran to Prevent Cardiovascular Events in High-risk Primary Prevention Patients.
Primary Prevention of Atherosclerotic Cardiovascular Disease
RecruitingPhase 3
Reducing Adverse Vascular Outcomes With Factor XI Inhibition in Adult Participants With Peripheral Artery Disease
Peripheral Artery Disease (PAD)
Recruiting
The THOR IDE Study
Peripheral Artery Disease, Peripheral Artery Stenosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A study testing Icosapent-ethyl ester capsules in people with Atherosclerosis Cardiovascular Disease, run by University of Sao Paulo.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 13 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Inar Castro Inar Castro Erger, Professor (+55(11)97429-3369, inar@usp.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Eicosapent ethyl ester (IPE) and high sensitivity C-Reactive Protein (hs-CRP) (time frame: From enrollment to the end of treatment at 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06720662, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2024.