Coronary Artery Disease, Coronary Atherosclerosis, Hyperlipidaemia, Hypertriglyceridaemia
Conditions
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
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.
Detailed description
This study consists of three main stages. First, a screening cohort will be established using CCTA. Individuals with 30% to 70% diameter narrowing in at least one major coronary artery-the left anterior descending, left circumflex, or right coronary artery-and at least one high-risk plaque feature will be considered for further screening. High-risk plaque features assessed by experienced imaging specialists include increased pericoronary fat attenuation, low-attenuation plaque, positive remodeling, spotty calcification, and the napkin-ring sign. This screening process is intended to identify appropriate and reliably characterized candidates for the randomized study. Eligible participants will undergo baseline 18F-NaF PET/CT imaging and then be randomly assigned in a 1:1 ratio using a centralized block randomization system. Participants in the intervention group will receive IPE 2 g twice daily for 12 months in addition to stable LDL-C-lowering therapy. Participants in the control group will continue stable LDL-C-lowering therapy without IPE. The LDL-C-lowering regimen should be stable for more than 4 weeks before randomization. After 12 months, participants in both groups will undergo follow-up CCTA and 18F-NaF PET/CT to evaluate changes in coronary plaque characteristics and disease activity. Follow-up will also include measurements of relevant plasma biomarkers and monitoring for major adverse cardiovascular events. Imaging data will be acquired using standardized procedures and interpreted by experienced imaging specialists.
Interventions
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.
DRUGStandard LDL-C-Lowering Therapy
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.
Sponsors
China National Center for Cardiovascular Diseases
Beijing Anzhen Hospital
Beijing Chao Yang Hospital
Beijing Municipal Health Commission
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
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.
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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. * Pregnancy or breastfeeding, or plans to become pregnant or breastfeed during study treatment or within 15 weeks after the last dose of study treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Maximum Target-to-Background Ratio of the Target Coronary Lesion | Baseline and Month 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline in TBRmax of the Target Coronary Lesion | Baseline and Month 12 | The target lesion is the coronary lesion with the highest TBRmax at baseline. Percentage change is calculated as \[(Month 12 TBRmax - baseline TBRmax) / baseline TBRmax\] × 100%. |
| Change From Baseline in SUVmax of the Target Coronary Lesion | Baseline and Month 12 | Change in the maximum standardized uptake value of the prespecified target coronary lesion, calculated as the Month 12 value minus the baseline value. |
| Change From Baseline in Total Volume of 18F-NaF-Positive Coronary Plaque | Baseline and Month 12 | Total volume of coronary plaque demonstrating positive 18F-NaF uptake, defined as TBRmax greater than 1.25. Change is calculated as the Month 12 volume minus the baseline volume. |
| Change From Baseline in the Number of 18F-NaF-Positive Coronary Segments | Baseline and Month 12 | Number of coronary artery segments with positive 18F-NaF uptake, defined as TBRmax greater than 1.25. Change is calculated as the Month 12 count minus the baseline count. |
| Change From Baseline in Pericoronary Fat Attenuation Index at the Target Plaque | Baseline and Month 12 | Pericoronary fat attenuation index (FAI), measured in Hounsfield units using CCTA at the location of the target plaque. Change is calculated as the Month 12 value minus the baseline value. |
| Change From Baseline in Percent Atheroma Volume at the Target Plaque | Baseline and Month 12 | Percent atheroma volume (PAV) will be measured using CCTA. Change is calculated as the Month 12 value minus the baseline value. |
| Change From Baseline in CCTA-Derived Coronary Plaque Component Volumes | Baseline and Month 12 | CCTA will be used to measure changes in total plaque, noncalcified plaque, calcified plaque, and low-attenuation noncalcified plaque volumes. For each component, change is calculated as the Month 12 volume minus the baseline volume. |
Countries
China
Contacts
CONTACTNaqiong Wu, Doctor
CONTACTZheng Yin, Master
Outcome results
None listed