YELLOW II Study: Reduction in Coronary Yellow Plaque, Lipids and Vascular Inflammation by Aggressive Lipid Lowering
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 91
- 试验地点
- 1
- 主要终点
- Correlation Between the Change in Fibrous Cap Thickness and Hs-CRP
研究概览
简要总结
Coronary artery disease (CAD) remains a leading cause of death in most countries. It is well known that the reduction of cholesterol levels by statin therapy is associated with significant decreases in plaque burden. REVERSAL, ASTEROID, and more recently the SATURN II trial showed that in patients with CAD, lipid lowering with atorvastatin or rosuvastatin respectively reduced progression of coronary atherosclerosis, even causing plaque regression of some lesions. CAD clinical events are related to plaque instability due to lipid content and activity within the atherosclerotic plaque. The investigators recently completed the YELLOW I study, and identified that intensive statin therapy (rosuvastatin 40mg) was associated with a reduction in the amount of lipid in obstructive coronary plaques, as measured by near-infrared spectroscopy (NIRS). The YELLOW II study is designed to expand and build upon these results, and to provide mechanistic insights into the potential benefits of intensive statin therapy on atherosclerotic plaques.
详细描述
YELLOW II is a single site study and will assess the regression of plaque lipid content and changes in plaque morphology from atherosclerotic lesions after high-dose statin therapy by utilizing NIRS, IVUS and optical coherency tomography (OCT) imaging modalities in the coronary arteries. We propose to image non-culprit coronary lesions using these modalities in patients with two or three diseased coronary vessels deemed to warrant intervention on clinical grounds. Thus, at the time of enrolment patients will undergo Percutaneous Coronary Intervention (PCI) of a non-study culprit lesion, and triple-modality imaging of the potential non-culprit ('YELLOW') lesion. If there is high baseline lipid content in the non-culprit YELLOW lesion (max 4mm LCBI > 150), patients will be formally entered into this study. Following this, all enrolled subjects will receive high-dose lipid lowering therapy (rosuvastatin 40mg daily). The non-culprit YELLOW lesion will undergo staged intervention 8-12 weeks following study enrolment and baseline imaging. At this time the YELLOW lesion will be reimaged to determine whether high-dose statin therapy caused a reduction in lipid content as assessed by NIRS, and other altered plaque morphology as assessed by OCT and IVUS. In addition, both at baseline and at the time of final non-culprit YELLOW lesion PCI, blood samples will be drawn during baseline and follow-up procedure to characterize reverse cholesterol transport by ability of patient HDL to accept cholesterol from cholesterol-laden (mouse J774) macrophage (cholesterol efflux) and the effect of patient HDL and apolipoprotein A1 on macrophage gene expression and migration.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients >18 years of age and willing to participate.
- •Fluency in either English or Spanish.
- •Stable patients who will undergo cardiac catheterization and PCI (intent to stent).
- •Patient is willing to go on high-dose cholesterol lowering medication for the duration of the study
- •Signed written Informed Consent.
- •Women of childbearing potential must agree to be on an acceptable method of birth control/contraceptive such as barrier method (condoms/diaphragm); hormonal contraceptives (birth control pills, implants (Norplant) or injections (Depo-Provera)); Intrauterine Device.
- •Proposed non-culprit YELLOW study lesion with max 4mm LCBI ≥ 150.
排除标准
- •Patients who have acute myocardial infarction (ST-segment elevation presentation, new Q waves or non-ST segment elevation with CK-MB > 5 times above the upper normal (31.5 ng/ml) within 72 hours).
- •Patients who are in cardiogenic shock.
- •Patients requiring coronary artery bypass graft surgery.
- •Patients with platelet count < 100,000 cell/mm
- •Patients who have co-morbidity which reduces life expectancy to one year.
- •Patients who are currently participating in another investigational drug/device study.
- •Patients with liver disease.
- •Patient with creatinine > 2.0 mg/dL.
- •Pregnant women and women of childbearing potential who intend to have children during the duration of the trial.
- •Patients having undergone heart transplantation, or those that may undergo heart transplantation during the study period.
- •Active autoimmune disease.
- •Nursing mothers
研究组 & 干预措施
rosuvastatin
All subjects will receive rosuvastatin 40mg/day
干预措施: rosuvastatin (Drug)
结局指标
主要结局
Correlation Between the Change in Fibrous Cap Thickness and Hs-CRP
时间窗: baseline and 8-12 weeks
Correlation between the change in plaque morphology composition by intravascular imaging with inflammatory cell activity.
Correlation Between Plaque Morphology and HDL Functionality
时间窗: baseline and 8-12 weeks
Correlation between the changes in plaque morphology composition by intravascular imaging with changes in HDL functionality. HDL functionality is measured by the Cholesterol Efflux Capacity (CEC). Plaque morphology is represented by the Fibrous Cap Thickness.
次要结局
- Plaque Morphology as Related to Haptoglobin(baseline and at 8-12 weeks)
- Correlation of Changes in Plaque Morphology(baseline and at 8-12 weeks)
- MACE(at 1 year)
- Change in Atheroma Volume(baseline and at 8-12 weeks)
- Biomarker Release(within 24 hrs of PCI)
- Maximal 4mm Lipid Core Burden Index (LCBI 4mm Max)(baseline and at 8-12 weeks)
- IVUS Imaging Measures(Baseline and 8 weeks)
- Lesion LCBI(at baseline and at 8-12 weeks)
- LCBI 4mm at Same Anatomical Site(at baseline and at 8-12 weeks)
- Correlation of Baseline Lipid Parameters With Baseline LCBI4mm Max(baseline)
- Fibrous Cap Thickness (FCT) by OCT(baseline and at 8-12 weeks)
- Inflammatory and Lipid Parameters(baseline and at 8-12 weeks)
- Mechanism of Reverse Cholesterol Transport(baseline and at 8-12 weeks)
研究者
Annapoorna Kini
Professor of Medicine
Icahn School of Medicine at Mount Sinai