Evolocumab in Acute Coronary Syndrome: A Double-Blind Randomized Placebo Controlled Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Percent Change in LDL-Cholesterol
研究概览
简要总结
Vascular and myocardial inflammation are significantly increased in Acute Coronary Syndrome (ACS) patients, are closely correlated to LDL-C levels, and are associated with these adverse consequences in the post-ACS patient population. Serum proprotein convertase subtilisin/kerin type 9 (PCSK9) levels are also increased in ACS, may raise LDL-C, and the investigators' pre-clinical studies indicate that PCSK9 is also a potent inducer of vascular inflammation. The addition of the PCSK9 antibody evolocumab, currently approved to lower LDL-C in certain patient populations, to current medical therapies would appear to be of particular benefit in an important subset of ACS patients, those with non-ST elevation myocardial infarction (NSTEMI) by markedly reducing LDL-C, stabilizing vulnerable plaque, and limiting inflammation-associated myocardial cell loss and resultant dysfunction.
详细描述
In a placebo-controlled, randomized double blind trial, the addition of evolocumab to standard care in NSTEMI patients (1) decreases LDL-C during hospitalization and at 30 days, (2) decreases vascular/plaque and myocardial inflammation as assessed by Positron Emission Tomography (PET) scanning at 30 days, and improves (3) serum markers of endothelial function at hospital discharge and at 30 days, and (4) echocardiographic assessment of left ventricular function at 30 days and six months.
This is the first PCSK9 inhibitor trial which examines these outcomes in the ACS patient population. It will provide valuable data on the extent and time course of LDL-C reduction as well as the impact of inhibition on inflammatory markers and on imaging assessment of vascular and myocardial inflammation, all of which may significantly impact important clinical outcomes in this high risk patient cohort.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Persons performing the PET imaging, laboratory technicians are all masked.
入排标准
- 年龄范围
- 25 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Non ST segment elevation myocardial infarction
- •Troponin I >/ 5.0 ng/dL
- •Permission of attending physician
排除标准
- •ST elevation myocardial infarction
- •Patients requiring invasive hemodynamic support
- •Scheduled for cardiac surgery
- •Current or prior treatment with a PCSK9 antibody
- •Current participation in an intervention clinical trial
- •Female of childbearing potential who has not used acceptable method(s) of birth control for at least one month prior to screening
- •Contraindication to statin therapy
- •Subject likely not able to complete protocol related visits or procedures
- •Latex allergy
- •History of hypersensitivity to any monoclonal antibody
研究组 & 干预措施
Placebo
Placebo administered subcutaneously using an autoinjector/pen in NSTEMI patients within 24 hours, or one day, of admission.
干预措施: Placebo (Drug)
Evolocumab
420 mg evolocumab administered subcutaneously using an autoinjector/pen in NSTEMI patients within 24 hours, or one day, of admission.
干预措施: Evolocumab (Drug)
结局指标
主要结局
Percent Change in LDL-Cholesterol
时间窗: Baseline to 30 days
Change From Baseline in Target to Background Ratio Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) Scans
时间窗: Baseline to 30 days
PET Imaging for Inflammation: Change from baseline in target to background ratio Fluorodeoxyglucose (FDG) PET scans in the myocardium.
次要结局
- Left Ventricular Volume as Assessed by Echocardiography(Baseline, day 30 and 6 months)
- Ejection Fraction as Assessed by Echocardiography(Baseline, day 30 and 6 months)
- Plasma Proprotein Convertase Subtilisin Kexin-9 (PCSK9) Levels (ng/ml)(Baseline, day 30 and 6 months)
- High Sensitivity C-reactive Protein (Hs-CRP) Serum Levels(Baseline, day 30 and 6 months)
- Serum Levels of Interleukin 10(Baseline, day 30 and 6 months)
- Change in Ejection Fraction as Assessed by Echocardiography(Baseline, day 30 and 6 months)
- Change in Plasma Proprotein Convertase Subtilisin Kexin-9 (PCSK9) Levels (ng/ml)(Baseline, day 30 and 6 months)
- Change in Left Ventricular Volume as Assessed by Echocardiography(Baseline, day 30 and 6 months)
- Change in Plasma Soluble Lectin-like Oxidized Low-density Lipoprotein Receptor-1 (LOX-1)(Baseline, day 30 and 6 months)
- PET-FDG Assessed Vascular Inflammation as Assessed by Standardized Uptake Value (SUV)(Baseline to day 30)
- Change in New York Heart Association (NYHA) Class(Baseline, day 30 and 6 months)
- Change in High Sensitivity C-reactive Protein (Hs-CRP) Serum Levels(Baseline, day 30 and 6 months)
- Change in Tumor Necrosis Factor (TNF)-Alpha Serum Levels(Baseline, day 30 and 6 months)
- Change in Plasma Levels of Interleukin 1(Baseline, day 30 and 6 months)
- Change in Serum Levels of Interleukin 6(Baseline, day 30 and 6 months)
- Change in Serum Levels of Interleukin 10(Baseline, day 30 and 6 months)
- Change in Canadian Angina Class(Baseline, 30 days, 6 months)