Impact of LDL-cholesterol Lowering on Platelet Activation
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Adenosine Di-phosphate (ADP) Induced, P2Y12 Dependent and Arachidonic Acid Induced Platelet Activation (P2Y12 Reaction Units (PRU))
研究概览
简要总结
The primary goal is to assess the impact of Evolocumab therapy on platelet function of familial hypercholesterolemia (FH) patients in a randomized, double blind study. Evolocumab is a humanized monoclonal antibody that targets circulating PCSK9, increases hepatic LDL receptor, decreases plasma LDL cholesterol and reduces risk of cardiovascular events. Evolocumab (brand name Rapatha) has been approved by FDA along with diet and maximally tolerated statin therapy in adults with FH or atherosclerotic heart or blood vessel problems, who need additional lowering of LDL cholesterol.
The secondary goal is to determine if platelet activation or the response to Evolocumab therapy is modified by rs3184504 polymorphism. The investigators believe that these investigations will complement ongoing studies to demonstrate that Evolocumab reduces athero-thrombotic risk and aid the decision-making as to whether Evolocumab can reduce the atherothrombotic risk in acute coronary syndrome (ACS) patients.
详细描述
Hyperlipidemia as exemplified by familial hypercholesterolemia is associated with increased platelet activation and an underlying pro-coagulant state. Hyperlipidemia primes platelets and increases platelet activation in response to various agonists. Plasma cholesterol levels appear to have a critical role in modulating platelet activity as hypercholesterolemia increases platelet activation more potently than hypertriglyceridemia. Increased platelet reactivity may contribute to the increased risk of atherothrombosis associated with hypercholesterolemia. Plasma levels of platelet activation markers such as thrombin-antithrombin complex (TAT), soluble P-selectin (sP-selectin), soluble CD40L (sCD40L) or P-selectin exposure at surface of platelets are increased in hypercholesterolemic patients. Increased levels of the platelet activation markers are associated with increased platelet membrane cholesterol content in hypercholesterolemia.Statins may show antithrombotic properties.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
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
- •Subjects who have a clinical diagnosis of familial hypercholesterolemia (FH)
- •Subjects who are referred to Dr. Ginsberg's Lipid Practice for treatment with PCSK9 inhibitor
- •Subjects with LDL cholesterol levels >100 mg/dl on baseline treatment with statins and/or ezetimibe
排除标准
- •Children under 18 years of age
研究组 & 干预措施
Evolocumab
Subjects will start with placebo and will receive Evolocumab 140 mg every 14 days starting Day 14 until Day 196.
干预措施: Evolocumab (Drug)
Placebo
Subjects will start with placebo and will receive Evolocumab 140 mg every 14 days starting Day 28 until Day 196.
干预措施: Evolocumab (Drug)
结局指标
主要结局
Adenosine Di-phosphate (ADP) Induced, P2Y12 Dependent and Arachidonic Acid Induced Platelet Activation (P2Y12 Reaction Units (PRU))
时间窗: Day 7, Day 14, Day 21, Day 28, Day 84
ADP- or arachidonic acid-stimulated platelet aggregation as assessed by the commercially-available VerifyNow P2Y12 (VerifyNow PRUTest) will be performed. Unit: PRU
Adenosine Di-phosphate (ADP) Induced, P2Y12 Dependent and Arachidonic Acid Induced Platelet Activation (Aspirin Reaction Unit (ARU))
时间窗: Day 7, Day 14, Day 21, Day 28, Day 84
ADP- or arachidonic acid-stimulated platelet aggregation as assessed by the commercially-available VerifyNow Aspirin assay (Accriva Diagnostics) will be performed. Unit: Aspirin Reaction Unit (ARU)
次要结局
未报告次要终点
研究者
Nan Wang
Associate Professor of Medical Sciences (in Medicine) at the Columbia University Medical Center
Columbia University