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.
調査の概要
詳細な説明
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.
研究の種類
介入
入学 (実際)
42
段階
- 適用できない
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
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
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：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
|
|
実験的：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
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Total Cholesterol Before and After Simvastatin/Ezetimibe Administration
時間枠：Baseline, 4 weeks and 8 weeks
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Total cholesterol concentration was measured by enzymatic assay
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Baseline, 4 weeks and 8 weeks
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Low-density Lipoprotein Cholesterol (LDLc) Before and After Simvastatin/Ezetimibe Administration
時間枠：Baseline, 4 weeks and 8 weeks
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Low-density lipoprotein cholesterol (LDLc) concentration was calculated using the method of Friedewald.
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Baseline, 4 weeks and 8 weeks
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High-density Lipoprotein Cholesterol (HDLc) Before and After Simvastatin/Ezetimibe Administration
時間枠：Baseline, 4 weeks and 8 weeks
|
High-density lipoprotein cholesterol (HDLc) concentration was measured using a direct method
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Baseline, 4 weeks and 8 weeks
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Triglycerides Before and After Simvastatin/Ezetimibe Administration
時間枠：Baseline, 4 weeks and 8 weeks
|
Triglyceride concentration were measured by enzymatic assay
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Baseline, 4 weeks and 8 weeks
|
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Non-HDL Cholesterol Before and After Simvastatin/Ezetimibe Administration
時間枠：Baseline, 4 weeks and 8 weeks
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Non-HDLc concentration was obtained by calculating the difference between total cholesterol and HDLc
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Baseline, 4 weeks and 8 weeks
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Low Density Lipoprotein Size Before and After Simvastatin/Ezetimibe Administration
時間枠：Baseline, 4 weeks and 8 weeks
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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.
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Baseline, 4 weeks and 8 weeks
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Apolipoprotein B Before and After Simvastatin/Ezetimibe Administration
時間枠：Baseline, 4 weeks and 8 weeks
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Levels of apolipoprotein B were determined by inmunonephelometry
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Baseline, 4 weeks and 8 weeks
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Levels of High-sensitive C-reactive Protein (hsCRP) Before and After Simvastatin/Ezetimibe Administration
時間枠：Baseline, 4 weeks and 8 weeks
|
Levels of high-sensitive C-reactive protein (hsCRP) were analysed by a latex-enhanced inmunonephelometric assay
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Baseline, 4 weeks and 8 weeks
|
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Levels of Interleukin-6 (IL-6) Before and After Simvastatin/Ezetimibe Administration
時間枠：Baseline, 4 weeks and 8 weeks
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Levels of proinflammatory cytokines (interleukin-6 (IL-6)) were analysed with a Luminex® 200™ system
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Baseline, 4 weeks and 8 weeks
|
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Levels of Tumor Necrosis Factor α (TNF-α) Before and After Simvastatin/Ezetimibe Administration
時間枠：Baseline, 4 weeks and 8 weeks
|
Levels of proinflammatory cytokines (tumor necrosis factor α (TNF-α)) were analysed with a Luminex® 200™ system
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Baseline, 4 weeks and 8 weeks
|
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Mitochondrial Oxygen (O2) Consumption Before and After Simvastatin/Ezetimibe Administration
時間枠：Baseline, 4 weeks and 8 weeks
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Oxidative stress markers (mitochondrial oxygen (O2) consumption) was measured at baseline and after treatment by Clark electrode
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Baseline, 4 weeks and 8 weeks
|
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Reactive Oxygen Species (ROS) Production Before and After Simvastatin/Ezetimibe Administration
時間枠：Baseline, 4 weeks and 8 weeks
|
Oxidative stress markers (Reactive oxygen species (ROS) production) was measured at baseline and after treatment by fluorometric techniques
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Baseline, 4 weeks and 8 weeks
|
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Membrane Potential Before and After Simvastatin/Ezetimibe Administration
時間枠：Baseline, 4 weeks and 8 weeks
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Oxidative stress markers (membrane potential) was measured at baseline and after treatment by fluorometric techniques
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Baseline, 4 weeks and 8 weeks
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Levels of Glutathione (GSH) Before and After Simvastatin/Ezetimibe Administration
時間枠：Baseline, 4 weeks and 8 weeks
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Oxidative stress markers (levels of glutathione (GSH)) was measured at baseline and after treatment by fluorometric techniques
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Baseline, 4 weeks and 8 weeks
|
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Leukocyte Rolling Flux Before and After Simvastatin/Ezetimibe Administration
時間枠：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.
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Baseline, 4 weeks and 8 weeks
|
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Leukocyte Adhesion Before and After Simvastatin/Ezetimibe Administration
時間枠：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.
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Baseline, 4 weeks and 8 weeks
|
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Leukocyte Rolling Velocity Before and After Simvastatin/Ezetimibe Administration
時間枠：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.
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Baseline, 4 weeks and 8 weeks
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Levels of Vascular Cell Adhesion Molecule 1 (VCAM-1) Before and After Simvastatin/Ezetimibe Administration
時間枠：Baseline, 4 weeks and 8 weeks
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The vascular cell adhesion molecule 1 (VCAM-1) was evaluated in serum by Luminex® 200™ system
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Baseline, 4 weeks and 8 weeks
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Levels of Intercellular Adhesion Molecule 1 (ICAM-1) Before and After Simvastatin/Ezetimibe Administration
時間枠：Baseline, 4 weeks and 8 weeks
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The intercellular adhesion molecule 1 (ICAM-1) was evaluated in serum by Luminex® 200™ system
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Baseline, 4 weeks and 8 weeks
|
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Levels of E-selectin Before and After Simvastatin/Ezetimibe Administration
時間枠：Baseline, 4 weeks and 8 weeks
|
E-selectin was evaluated in serum by Luminex® 200™ system
|
Baseline, 4 weeks and 8 weeks
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
捜査官
- 主任研究者：Antonio Hernández, MD, Phd、FISABIO - University Hospital Dr Peset
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- 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.
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2009年1月1日
一次修了 (実際)
2011年12月1日
研究の完了 (実際)
2011年12月1日
試験登録日
最初に提出
2014年11月25日
QC基準を満たした最初の提出物
2014年11月26日
最初の投稿 (見積もり)
2014年12月2日
学習記録の更新
投稿された最後の更新 (実際)
2018年3月8日
QC基準を満たした最後の更新が送信されました
2018年2月6日
最終確認日
2018年2月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。