Effects of Simvastatin and Ezetimibe on Cardiovascular Risk Markers in Patients With Dyslipidemia
2018年2月6日 更新者：Antonio Hernandez Mijares、Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
Study of Lipoprotein Subfractions, Inflammation, Oxidative Stress and Endothelial Function After Treatment With Simvastatin and Ezetimibe Administered Alone and in Combination in Hyperlipidemic Patients
Coadministration of drugs is common in the pharmacologic treatment of dyslipidemia, with statins and ezetimibe generally constituting the medication of choice.
By acting at different levels, the combination of these drugs allows the therapeutic objective to be achieved.
However, it is not known how these drugs qualitatively affect the composition of lipoprotein subfractions, which differ in size and atherogenic potential.
The investigators set out to evaluate this effect as well as their effects on inflammatory, oxidative stress and endothelial function parameters.
研究概览
详细说明
The study consisted of a randomised parallel trial and took place during a period of 2 months.
A total of 42 hyperlipidemic patients were randomly assigned to one of 2 groups: one received simvastatin (40 mg/day) and the other received ezetimibe (10 mg/day) for 4 weeks, after which both groups were administered combined therapy for an additional 4-week period.
Lipid profile, lipoprotein subfractions of LDL and HDL, inflammatory, oxidative stress and endothelial function parameters were evaluated.
研究类型
介入性
注册 (实际的)
42
阶段
- 不适用
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- LDL cholesterol concentration of between 160-190 mg/dl in patients with less than 2 cardiovascular risk factors
- LDL concentration of between 130-160 mg/dl in patients that presented 2 or more cardiovascular risk factors.
Cardiovascular risk factors were defined as: age (≥ 45 years in men and ≥55 years in women), a smoking habit, hypertension (≥140/90 mmHg), diabetes mellitus, a high-density lipoprotein (HDL) cholesterol concentration of ≤ 40mg/dl, and a family history of cardiovascular disease.
Exclusion Criteria:
- Triglyceride concentration > 400 mg/dl
- Diabetes Mellitus
- Kidney, liver, or thyroid disease
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：Simvastatin
Hyperlipidemic patients received simvastatin (40 mg/day) for 4 weeks, after they were administered combined therapy (simvastatin, 40 mg/day plus ezetimibe,10 mg/day) for an additional 4-week period.
Lipid profile, lipoprotein subfractions of LDL and HDL, inflammatory, oxidative stress and endothelial function parameters were evaluated.
|
simvastatin (40 mg/day) for 4 weeks
combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
|
|
实验性的：Ezetimibe
Hyperlipidemic patients received ezetimibe (10 mg/day) for 4 weeks, after they were administered combined therapy (simvastatin, 40 mg/day plus ezetimibe,10 mg/day) for an additional 4-week period.
Lipid profile, lipoprotein subfractions of LDL and HDL, inflammatory, oxidative stress and endothelial function parameters were evaluated.
|
combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
ezetimibe (10 mg/day) for 4 weeks
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Total Cholesterol Before and After Simvastatin/Ezetimibe Administration
大体时间：Baseline, 4 weeks and 8 weeks
|
Total cholesterol concentration was measured by enzymatic assay
|
Baseline, 4 weeks and 8 weeks
|
|
Low-density Lipoprotein Cholesterol (LDLc) Before and After Simvastatin/Ezetimibe Administration
大体时间：Baseline, 4 weeks and 8 weeks
|
Low-density lipoprotein cholesterol (LDLc) concentration was calculated using the method of Friedewald.
|
Baseline, 4 weeks and 8 weeks
|
|
High-density Lipoprotein Cholesterol (HDLc) Before and After Simvastatin/Ezetimibe Administration
大体时间：Baseline, 4 weeks and 8 weeks
|
High-density lipoprotein cholesterol (HDLc) concentration was measured using a direct method
|
Baseline, 4 weeks and 8 weeks
|
|
Triglycerides Before and After Simvastatin/Ezetimibe Administration
大体时间：Baseline, 4 weeks and 8 weeks
|
Triglyceride concentration were measured by enzymatic assay
|
Baseline, 4 weeks and 8 weeks
|
|
Non-HDL Cholesterol Before and After Simvastatin/Ezetimibe Administration
大体时间：Baseline, 4 weeks and 8 weeks
|
Non-HDLc concentration was obtained by calculating the difference between total cholesterol and HDLc
|
Baseline, 4 weeks and 8 weeks
|
|
Low Density Lipoprotein Size Before and After Simvastatin/Ezetimibe Administration
大体时间：Baseline, 4 weeks and 8 weeks
|
LDL subfractions were separated by high-resolution polyacrylamide gel tubes using the Lipoprint® system.
The LDL electrophoretic profile allows 2 patterns to be defined: pattern A or large and buoyant LDL, and pattern non-A or small and dense LDL.
|
Baseline, 4 weeks and 8 weeks
|
|
Apolipoprotein B Before and After Simvastatin/Ezetimibe Administration
大体时间：Baseline, 4 weeks and 8 weeks
|
Levels of apolipoprotein B were determined by inmunonephelometry
|
Baseline, 4 weeks and 8 weeks
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Levels of High-sensitive C-reactive Protein (hsCRP) Before and After Simvastatin/Ezetimibe Administration
大体时间：Baseline, 4 weeks and 8 weeks
|
Levels of high-sensitive C-reactive protein (hsCRP) were analysed by a latex-enhanced inmunonephelometric assay
|
Baseline, 4 weeks and 8 weeks
|
|
Levels of Interleukin-6 (IL-6) Before and After Simvastatin/Ezetimibe Administration
大体时间：Baseline, 4 weeks and 8 weeks
|
Levels of proinflammatory cytokines (interleukin-6 (IL-6)) were analysed with a Luminex® 200™ system
|
Baseline, 4 weeks and 8 weeks
|
|
Levels of Tumor Necrosis Factor α (TNF-α) Before and After Simvastatin/Ezetimibe Administration
大体时间：Baseline, 4 weeks and 8 weeks
|
Levels of proinflammatory cytokines (tumor necrosis factor α (TNF-α)) were analysed with a Luminex® 200™ system
|
Baseline, 4 weeks and 8 weeks
|
|
Mitochondrial Oxygen (O2) Consumption Before and After Simvastatin/Ezetimibe Administration
大体时间：Baseline, 4 weeks and 8 weeks
|
Oxidative stress markers (mitochondrial oxygen (O2) consumption) was measured at baseline and after treatment by Clark electrode
|
Baseline, 4 weeks and 8 weeks
|
|
Reactive Oxygen Species (ROS) Production Before and After Simvastatin/Ezetimibe Administration
大体时间：Baseline, 4 weeks and 8 weeks
|
Oxidative stress markers (Reactive oxygen species (ROS) production) was measured at baseline and after treatment by fluorometric techniques
|
Baseline, 4 weeks and 8 weeks
|
|
Membrane Potential Before and After Simvastatin/Ezetimibe Administration
大体时间：Baseline, 4 weeks and 8 weeks
|
Oxidative stress markers (membrane potential) was measured at baseline and after treatment by fluorometric techniques
|
Baseline, 4 weeks and 8 weeks
|
|
Levels of Glutathione (GSH) Before and After Simvastatin/Ezetimibe Administration
大体时间：Baseline, 4 weeks and 8 weeks
|
Oxidative stress markers (levels of glutathione (GSH)) was measured at baseline and after treatment by fluorometric techniques
|
Baseline, 4 weeks and 8 weeks
|
|
Leukocyte Rolling Flux Before and After Simvastatin/Ezetimibe Administration
大体时间：Baseline, 4 weeks and 8 weeks
|
Interactions between leukocytes and human umbilical vein endothelial cells were evaluated by flow chamber microscopy.
Leukocyte rolling was estimated as the number of leukocytes rolling over 100 μm2 of the endothelial monolayer during a 1-min period.
|
Baseline, 4 weeks and 8 weeks
|
|
Leukocyte Adhesion Before and After Simvastatin/Ezetimibe Administration
大体时间：Baseline, 4 weeks and 8 weeks
|
Interactions between leukocytes and human umbilical vein endothelial cells were evaluated by flow chamber microscopy.
Adhesion was evaluated by counting the number of polymorphonuclear cells that maintained stable contact with human umbilical vein endothelial cells (HUVEC) for 30 seconds.
|
Baseline, 4 weeks and 8 weeks
|
|
Leukocyte Rolling Velocity Before and After Simvastatin/Ezetimibe Administration
大体时间：Baseline, 4 weeks and 8 weeks
|
Interactions between leukocytes and human umbilical vein endothelial cells were evaluated by flow chamber microscopy.The rolling velocity in the field of focus was determined by measuring the time required by 20 consecutive leukocytes to cover a distance of 100 μm.
|
Baseline, 4 weeks and 8 weeks
|
|
Levels of Vascular Cell Adhesion Molecule 1 (VCAM-1) Before and After Simvastatin/Ezetimibe Administration
大体时间：Baseline, 4 weeks and 8 weeks
|
The vascular cell adhesion molecule 1 (VCAM-1) was evaluated in serum by Luminex® 200™ system
|
Baseline, 4 weeks and 8 weeks
|
|
Levels of Intercellular Adhesion Molecule 1 (ICAM-1) Before and After Simvastatin/Ezetimibe Administration
大体时间：Baseline, 4 weeks and 8 weeks
|
The intercellular adhesion molecule 1 (ICAM-1) was evaluated in serum by Luminex® 200™ system
|
Baseline, 4 weeks and 8 weeks
|
|
Levels of E-selectin Before and After Simvastatin/Ezetimibe Administration
大体时间：Baseline, 4 weeks and 8 weeks
|
E-selectin was evaluated in serum by Luminex® 200™ system
|
Baseline, 4 weeks and 8 weeks
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员：Antonio Hernández, MD, Phd、FISABIO - University Hospital Dr Peset
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
- Berneis K, Rizzo M, Berthold HK, Spinas GA, Krone W, Gouni-Berthold I. Ezetimibe alone or in combination with simvastatin increases small dense low-density lipoproteins in healthy men: a randomized trial. Eur Heart J. 2010 Jul;31(13):1633-9. doi: 10.1093/eurheartj/ehq181. Epub 2010 Jun 6.
- Florentin M, Liberopoulos EN, Moutzouri E, Rizos CV, Tselepis AD, Elisaf MS. The effect of simvastatin alone versus simvastatin plus ezetimibe on the concentration of small dense low-density lipoprotein cholesterol in subjects with primary hypercholesterolemia. Curr Med Res Opin. 2011 Mar;27(3):685-92. doi: 10.1185/03007995.2010.546394. Epub 2011 Jan 27.
- Bays HE, Ose L, Fraser N, Tribble DL, Quinto K, Reyes R, Johnson-Levonas AO, Sapre A, Donahue SR; Ezetimibe Study Group. A multicenter, randomized, double-blind, placebo-controlled, factorial design study to evaluate the lipid-altering efficacy and safety profile of the ezetimibe/simvastatin tablet compared with ezetimibe and simvastatin monotherapy in patients with primary hypercholesterolemia. Clin Ther. 2004 Nov;26(11):1758-73. doi: 10.1016/j.clinthera.2004.11.016.
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2009年1月1日
初级完成 (实际的)
2011年12月1日
研究完成 (实际的)
2011年12月1日
研究注册日期
首次提交
2014年11月25日
首先提交符合 QC 标准的
2014年11月26日
首次发布 (估计)
2014年12月2日
研究记录更新
最后更新发布 (实际的)
2018年3月8日
上次提交的符合 QC 标准的更新
2018年2月6日
最后验证
2018年2月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.