Icosapent Ethyl for High-Risk Coronary Plaques Assessed by 18F-NaF PET/CT

NCT07762755 | Not Yet Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 2026-3220
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized controlled study will evaluate whether icosapent ethyl (IPE) can improve and stabilize high-risk coronary plaques in patients receiving stable low-density lipoprotein cholesterol (LDL-C)-lowering therapy. Potential participants will have coronary plaques identified by coronary computed tomography angiography (CCTA), with 30% to 70% narrowing in at least one major coronary artery and at least one high-risk plaque feature. After baseline imaging with fluorine-18 sodium fluoride positron emission tomography/computed tomography (18F-NaF PET/CT), eligible participants will be randomly assigned in a 1:1 ratio to receive either IPE 2 g twice daily plus standard LDL-C-lowering therapy or standard LDL-C-lowering therapy alone for 12 months. At the end of treatment, participants will undergo repeat CCTA and 18F-NaF PET/CT. Blood biomarkers and major adverse cardiovascular events will also be assessed during follow-up.

Conditions

Coronary Artery Disease; Hyperlipidaemia; Hypertriglyceridaemia; Coronary Atherosclerosis

Keywords

Icosapent Ethyl; IPE; High-Risk Coronary Plaque; Coronary Plaque Stabilization; Coronary Atherosclerosis; Intermediate Coronary Stenosis; 18F-Sodium Fluoride PET/CT; 18F-NaF PET/CT; Coronary Computed Tomography Angiography; CCTA; Coronary Microcalcification; Pericoronary Fat Attenuation Index

Outcome Measures

Primary Outcomes (1)

• Absolute Change From Baseline in Maximum Target-to-Background Ratio of the Target Coronary Lesion

  The target lesion is defined as the coronary lesion with the highest maximum target-to-background ratio (TBRmax) at baseline. TBRmax is calculated as the maximum standardized uptake value (SUVmax) of the target lesion divided by the mean standardized uptake value (SUVmean) of the blood-pool background measured in the right atrium, superior vena cava, or inferior vena cava. Absolute change is calculated as the Month 12 TBRmax minus the baseline TBRmax.

  Baseline and Month 12

Secondary Outcomes (7)

• Percentage Change From Baseline in TBRmax of the Target Coronary Lesion

  Baseline and Month 12

• Change From Baseline in SUVmax of the Target Coronary Lesion

  Baseline and Month 12

• Change From Baseline in Total Volume of 18F-NaF-Positive Coronary Plaque

  Baseline and Month 12

• Change From Baseline in the Number of 18F-NaF-Positive Coronary Segments

  Baseline and Month 12

• Change From Baseline in Pericoronary Fat Attenuation Index at the Target Plaque

  Baseline and Month 12

Other Outcomes (5)

• Change in Plasma triglycerides Levels From Baseline to Month 12

  Baseline and Month 12

• Percentage Change From Baseline in Plasma High-Sensitivity C-Reactive Protein Level

  Baseline and Month 12

• Change in Plasma Eicosapentaenoic Acid Level From Baseline to Month 12

  Baseline and Month 12

Study Arms (2)

Icosapent Ethyl Plus Standard LDL-C-Lowering Therapy

EXPERIMENTAL

Participants will receive oral icosapent ethyl 2 g twice daily for 12 months in addition to their stable LDL-C-lowering therapy. CCTA and 18F-NaF PET/CT will be performed at baseline and after 12 months, together with biomarker and clinical event follow-up.

Drug: icosapent ethyl (IPE); Drug: Standard LDL-C-Lowering Therapy

Standard LDL-C-Lowering Therapy Alone

ACTIVE COMPARATOR

Participants will continue their stable LDL-C-lowering therapy for 12 months without receiving icosapent ethyl. CCTA and 18F-NaF PET/CT will be performed at baseline and after 12 months, together with biomarker and clinical event follow-up.

Drug: Standard LDL-C-Lowering Therapy

Interventions

icosapent ethyl (IPE) DRUG

Icosapent ethyl will be administered orally at a dose of 2 g twice daily (total daily dose of 4 g) for 12 months, in addition to stable LDL-C-lowering therapy.

Also known as: IPE, Ethyl Eicosapentaenoate, Eicosapentaenoic Acid Ethyl Ester

Icosapent Ethyl Plus Standard LDL-C-Lowering Therapy

Standard LDL-C-Lowering Therapy DRUG

Participants will continue an individualized, stable LDL-C-lowering regimen throughout the 12-month study period. The LDL-C-lowering regimen must have remained stable for more than 4 weeks before randomization. This background therapy will be administered in both study arms.

Icosapent Ethyl Plus Standard LDL-C-Lowering Therapy; Standard LDL-C-Lowering Therapy Alone

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participants aged 18 to 75 years.
• Ability to understand the study and provide written informed consent before enrollment.
• Receiving a stable lipid-lowering regimen before enrollment, with the type and dose of statin therapy remaining unchanged for at least 4 weeks.
• Fasting triglyceride level below 5.6 mmol/L.
• Presence of at least one of the following high-risk plaque features on coronary computed tomography angiography (CCTA):Pericoronary fat attenuation index greater than -70.1 Hounsfield units;
• Low-attenuation plaque below 30 Hounsfield units;
• Positive remodeling index greater than 1.1;
• Spotty calcification;
• or Napkin-ring sign, defined as a low-attenuation plaque core surrounded by a rim of higher attenuation.

You may not qualify if:

• Current participation in another investigational drug, device, or procedure study, or receipt of an investigational drug or device within 4 weeks before enrollment.
• Treatment with icosapent ethyl within 12 months before enrollment.
• Known intolerance or hypersensitivity to icosapent ethyl or fish oil.
• A previous diagnosis of homozygous familial hypercholesterolemia or hyperlipidemia requiring hemodialysis.
• Myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass grafting, or stroke within 3 months before enrollment;
• Planned cardiac surgery, percutaneous coronary intervention, or carotid artery stenting, or planned major noncardiac surgery during the study.
• A known contraindication or limitation to PET/CT, including exceeding scanner weight limits or having a device, carotid or aortic stent, or vascular graft that may cause imaging artifacts.
• Autoimmune disease, vasculitis, or active inflammatory disease.
• Serious infection within 1 month before enrollment or a current infection requiring intravenous antibiotic treatment.
• Use within 6 weeks before enrollment or current use of medications that may significantly affect plaque inflammation, including oral, rectal, or injectable corticosteroids or immunosuppressive agents, such as cyclosporine, methotrexate, tacrolimus, azathioprine, antithymocyte globulin, sirolimus, anti-tumor necrosis factor agents such as infliximab, anti-interleukin-6 therapy such as tocilizumab, or anti-interleukin-1 therapy.
• Use within 6 weeks before enrollment or current use of aspirin at a dose greater than 325 mg/day or nonsteroidal anti-inflammatory drugs at a dose greater than 1,000 mg/day.
• Treatment within 12 months before enrollment with a cholesteryl ester transfer protein inhibitor, including anacetrapib, dalcetrapib, or evacetrapib, or with mipomersen or lomitapide.
• Known clinically significant systemic disease, including hepatic, renal, hematologic, or malignant disease, or any other clinically significant comorbidity that may interfere with study participation or study assessments.
• History of malignancy within the previous 5 years, except nonmelanoma skin cancer, cervical carcinoma in situ, ductal carcinoma in situ of the breast, or stage I prostate cancer.
• Inability or anticipated inability to complete all protocol-required visits or procedures, or any condition that may make the participant unreliable for study participation, including alcohol or other substance abuse within the previous year or a psychiatric disorder.

Sponsors & Collaborators

• China National Center for Cardiovascular Diseases: lead
• Beijing Anzhen Hospital: collaborator
• Beijing Chao Yang Hospital: collaborator
• Beijing Municipal Health Commission: collaborator

Study Sites (1)

Fuwai Hospital

Beijing, Beijing Municipality, 100037, China

Location

Related Publications (5)

• Moss A, Daghem M, Tzolos E, Meah MN, Wang KL, Bularga A, Adamson PD, Kwiecinski J, Fletcher A, Dawson D, Arumugam P, Sabharwal N, Greenwood JP, Townend JN, Calvert PA, Rudd JHF, Berman D, Verjans J, Slomka P, Dey D, Forsyth L, Murdoch L, Lee RJ, Lewis S, Mills NL, van Beek EJR, Williams MC, Dweck MR, Newby DE; PREFFIR Investigators. Coronary Atherosclerotic Plaque Activity and Future Coronary Events. JAMA Cardiol. 2023 Aug 1;8(8):755-764. doi: 10.1001/jamacardio.2023.1729.

  PMID: 37379010 BACKGROUND

• Sayah N, Bhatt DL, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Jiao L, Pineda AL, Doyle RT Jr, Tardif JC, Ballantyne CM, Steg PG. Icosapent ethyl following acute coronary syndrome: the REDUCE-IT trial. Eur Heart J. 2024 Apr 1;45(13):1173-1176. doi: 10.1093/eurheartj/ehad889. No abstract available.

  PMID: 38252107 BACKGROUND

• Budoff MJ, Bhatt DL, Kinninger A, Lakshmanan S, Muhlestein JB, Le VT, May HT, Shaikh K, Shekar C, Roy SK, Tayek J, Nelson JR. Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: final results of the EVAPORATE trial. Eur Heart J. 2020 Oct 21;41(40):3925-3932. doi: 10.1093/eurheartj/ehaa652.

  PMID: 32860032 BACKGROUND

• Yang S, Hoshino M, Koo BK, Yonetsu T, Zhang J, Hwang D, Shin ES, Doh JH, Nam CW, Wang J, Chen S, Tanaka N, Matsuo H, Kubo T, Chang HJ, Kakuta T, Narula J. Relationship of Plaque Features at Coronary CT to Coronary Hemodynamics and Cardiovascular Events. Radiology. 2022 Dec;305(3):578-587. doi: 10.1148/radiol.213271. Epub 2022 Aug 16.

  PMID: 35972355 BACKGROUND

• Gallone G, Bellettini M, Gatti M, Tore D, Bruno F, Scudeler L, Cusenza V, Lanfranchi A, Angelini A, de Filippo O, Iannaccone M, Baldetti L, Audisio K, Demetres M, Risi G, Rizzello G, Porto I, Fonio P, Prati F, Williams MC, Koo BK, Pontone G, Depaoli A, Libby P, Stone GW, Narula J, de Ferrari GM, d'Ascenzo F. Coronary Plaque Characteristics Associated With Major Adverse Cardiovascular Events in Atherosclerotic Patients and Lesions: A Systematic Review and Meta-Analysis. JACC Cardiovasc Imaging. 2023 Dec;16(12):1584-1604. doi: 10.1016/j.jcmg.2023.08.006. Epub 2023 Oct 4.

  PMID: 37804276 BACKGROUND

MeSH Terms

Conditions

Coronary Artery Disease; Hyperlipidemias; Hypertriglyceridemia

Interventions

eicosapentaenoic acid ethyl ester

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Naqiong Wu, Doctor

CONTACT

+86 13501139869; fuwainaqiongwu@163.com

Zheng Yin, Master

CONTACT

+8615359270767; yinzheng@fuwai.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Participants, care providers, and investigators will not be masked. Outcome assessors responsible for evaluating CCTA and 18F-NaF PET/CT images and other study outcomes will be blinded to treatment allocation. In addition, the statistician performing the statistical analyses will be blinded to treatment allocation. Treatment groups will be identified using coded labels, and the allocation code will not be disclosed to the outcome assessors or statistician until the prespecified assessments and statistical analyses have been completed.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Eligible participants will be randomized in a 1:1 ratio to two parallel groups. Both groups will continue stable LDL-C-lowering therapy. The intervention group will additionally receive icosapent ethyl 2 g twice daily for 12 months, while the control group will receive no icosapent ethyl. Participants in both groups will undergo the same baseline and 12-month imaging and follow-up assessments.

Study Record Dates

• First Submitted: July 29, 2026
• First Posted: August 13, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029
• Last Updated: August 13, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)