A Randomized Controlled Trial Evaluating the Effect of Icosapent Ethyl on High-Risk Coronary Plaques Using 18F-Sodium Fluoride PET/CT
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Absolute Change From Baseline in Maximum Target-to-Background Ratio of the Target Coronary Lesion
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Icosapent Ethyl Plus Standard LDL-C-Lowering Therapy
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.
干预措施: icosapent ethyl (IPE) (Drug)
Icosapent Ethyl Plus Standard LDL-C-Lowering Therapy
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.
干预措施: Standard LDL-C-Lowering Therapy (Drug)
Standard LDL-C-Lowering Therapy Alone
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.
干预措施: Standard LDL-C-Lowering Therapy (Drug)
结局指标
主要结局
Absolute Change From Baseline in Maximum Target-to-Background Ratio of the Target Coronary Lesion
时间窗: 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.
次要结局
- 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)
- Change From Baseline in Percent Atheroma Volume at the Target Plaque(Baseline and Month 12)
- Change From Baseline in CCTA-Derived Coronary Plaque Component Volumes(Baseline and Month 12)