search
Back to results

Effects of Simvastatin and Ezetimibe on Cardiovascular Risk Markers in Patients With Dyslipidemia

Primary Purpose

Dyslipidemia

Status
Completed
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Simvastatin
Ezetimibe
Simvastatin + Ezetimibe
Sponsored by
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dyslipidemia focused on measuring Dyslipidemia, Simvastatin, Ezetimibe, Lipid profile, Inflammation, Oxidative stress, Endothelial function

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    Simvastatin

    Ezetimibe

    Arm Description

    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.

    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.

    Outcomes

    Primary Outcome Measures

    Total Cholesterol Before and After Simvastatin/Ezetimibe Administration
    Total cholesterol concentration was measured by enzymatic assay
    Low-density Lipoprotein Cholesterol (LDLc) Before and After Simvastatin/Ezetimibe Administration
    Low-density lipoprotein cholesterol (LDLc) concentration was calculated using the method of Friedewald.
    High-density Lipoprotein Cholesterol (HDLc) Before and After Simvastatin/Ezetimibe Administration
    High-density lipoprotein cholesterol (HDLc) concentration was measured using a direct method
    Triglycerides Before and After Simvastatin/Ezetimibe Administration
    Triglyceride concentration were measured by enzymatic assay
    Non-HDL Cholesterol Before and After Simvastatin/Ezetimibe Administration
    Non-HDLc concentration was obtained by calculating the difference between total cholesterol and HDLc
    Low Density Lipoprotein Size Before and After Simvastatin/Ezetimibe Administration
    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.
    Apolipoprotein B Before and After Simvastatin/Ezetimibe Administration
    Levels of apolipoprotein B were determined by inmunonephelometry

    Secondary Outcome Measures

    Levels of High-sensitive C-reactive Protein (hsCRP) Before and After Simvastatin/Ezetimibe Administration
    Levels of high-sensitive C-reactive protein (hsCRP) were analysed by a latex-enhanced inmunonephelometric assay
    Levels of Interleukin-6 (IL-6) Before and After Simvastatin/Ezetimibe Administration
    Levels of proinflammatory cytokines (interleukin-6 (IL-6)) were analysed with a Luminex® 200™ system
    Levels of Tumor Necrosis Factor α (TNF-α) Before and After Simvastatin/Ezetimibe Administration
    Levels of proinflammatory cytokines (tumor necrosis factor α (TNF-α)) were analysed with a Luminex® 200™ system
    Mitochondrial Oxygen (O2) Consumption Before and After Simvastatin/Ezetimibe Administration
    Oxidative stress markers (mitochondrial oxygen (O2) consumption) was measured at baseline and after treatment by Clark electrode
    Reactive Oxygen Species (ROS) Production Before and After Simvastatin/Ezetimibe Administration
    Oxidative stress markers (Reactive oxygen species (ROS) production) was measured at baseline and after treatment by fluorometric techniques
    Membrane Potential Before and After Simvastatin/Ezetimibe Administration
    Oxidative stress markers (membrane potential) was measured at baseline and after treatment by fluorometric techniques
    Levels of Glutathione (GSH) Before and After Simvastatin/Ezetimibe Administration
    Oxidative stress markers (levels of glutathione (GSH)) was measured at baseline and after treatment by fluorometric techniques
    Leukocyte Rolling Flux Before and After Simvastatin/Ezetimibe Administration
    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.
    Leukocyte Adhesion Before and After Simvastatin/Ezetimibe Administration
    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.
    Leukocyte Rolling Velocity Before and After Simvastatin/Ezetimibe Administration
    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.
    Levels of Vascular Cell Adhesion Molecule 1 (VCAM-1) Before and After Simvastatin/Ezetimibe Administration
    The vascular cell adhesion molecule 1 (VCAM-1) was evaluated in serum by Luminex® 200™ system
    Levels of Intercellular Adhesion Molecule 1 (ICAM-1) Before and After Simvastatin/Ezetimibe Administration
    The intercellular adhesion molecule 1 (ICAM-1) was evaluated in serum by Luminex® 200™ system
    Levels of E-selectin Before and After Simvastatin/Ezetimibe Administration
    E-selectin was evaluated in serum by Luminex® 200™ system

    Full Information

    First Posted
    November 25, 2014
    Last Updated
    February 6, 2018
    Sponsor
    Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT02304926
    Brief Title
    Effects of Simvastatin and Ezetimibe on Cardiovascular Risk Markers in Patients With Dyslipidemia
    Official Title
    Study of Lipoprotein Subfractions, Inflammation, Oxidative Stress and Endothelial Function After Treatment With Simvastatin and Ezetimibe Administered Alone and in Combination in Hyperlipidemic Patients
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2018
    Overall Recruitment Status
    Completed
    Study Start Date
    January 2009 (undefined)
    Primary Completion Date
    December 2011 (Actual)
    Study Completion Date
    December 2011 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    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.
    Detailed Description
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Dyslipidemia
    Keywords
    Dyslipidemia, Simvastatin, Ezetimibe, Lipid profile, Inflammation, Oxidative stress, Endothelial function

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    42 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Simvastatin
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    Ezetimibe
    Arm Type
    Experimental
    Arm Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    Simvastatin
    Intervention Description
    simvastatin (40 mg/day) for 4 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    Ezetimibe
    Intervention Description
    ezetimibe (10 mg/day) for 4 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    Simvastatin + Ezetimibe
    Intervention Description
    combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
    Primary Outcome Measure Information:
    Title
    Total Cholesterol Before and After Simvastatin/Ezetimibe Administration
    Description
    Total cholesterol concentration was measured by enzymatic assay
    Time Frame
    Baseline, 4 weeks and 8 weeks
    Title
    Low-density Lipoprotein Cholesterol (LDLc) Before and After Simvastatin/Ezetimibe Administration
    Description
    Low-density lipoprotein cholesterol (LDLc) concentration was calculated using the method of Friedewald.
    Time Frame
    Baseline, 4 weeks and 8 weeks
    Title
    High-density Lipoprotein Cholesterol (HDLc) Before and After Simvastatin/Ezetimibe Administration
    Description
    High-density lipoprotein cholesterol (HDLc) concentration was measured using a direct method
    Time Frame
    Baseline, 4 weeks and 8 weeks
    Title
    Triglycerides Before and After Simvastatin/Ezetimibe Administration
    Description
    Triglyceride concentration were measured by enzymatic assay
    Time Frame
    Baseline, 4 weeks and 8 weeks
    Title
    Non-HDL Cholesterol Before and After Simvastatin/Ezetimibe Administration
    Description
    Non-HDLc concentration was obtained by calculating the difference between total cholesterol and HDLc
    Time Frame
    Baseline, 4 weeks and 8 weeks
    Title
    Low Density Lipoprotein Size Before and After Simvastatin/Ezetimibe Administration
    Description
    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.
    Time Frame
    Baseline, 4 weeks and 8 weeks
    Title
    Apolipoprotein B Before and After Simvastatin/Ezetimibe Administration
    Description
    Levels of apolipoprotein B were determined by inmunonephelometry
    Time Frame
    Baseline, 4 weeks and 8 weeks
    Secondary Outcome Measure Information:
    Title
    Levels of High-sensitive C-reactive Protein (hsCRP) Before and After Simvastatin/Ezetimibe Administration
    Description
    Levels of high-sensitive C-reactive protein (hsCRP) were analysed by a latex-enhanced inmunonephelometric assay
    Time Frame
    Baseline, 4 weeks and 8 weeks
    Title
    Levels of Interleukin-6 (IL-6) Before and After Simvastatin/Ezetimibe Administration
    Description
    Levels of proinflammatory cytokines (interleukin-6 (IL-6)) were analysed with a Luminex® 200™ system
    Time Frame
    Baseline, 4 weeks and 8 weeks
    Title
    Levels of Tumor Necrosis Factor α (TNF-α) Before and After Simvastatin/Ezetimibe Administration
    Description
    Levels of proinflammatory cytokines (tumor necrosis factor α (TNF-α)) were analysed with a Luminex® 200™ system
    Time Frame
    Baseline, 4 weeks and 8 weeks
    Title
    Mitochondrial Oxygen (O2) Consumption Before and After Simvastatin/Ezetimibe Administration
    Description
    Oxidative stress markers (mitochondrial oxygen (O2) consumption) was measured at baseline and after treatment by Clark electrode
    Time Frame
    Baseline, 4 weeks and 8 weeks
    Title
    Reactive Oxygen Species (ROS) Production Before and After Simvastatin/Ezetimibe Administration
    Description
    Oxidative stress markers (Reactive oxygen species (ROS) production) was measured at baseline and after treatment by fluorometric techniques
    Time Frame
    Baseline, 4 weeks and 8 weeks
    Title
    Membrane Potential Before and After Simvastatin/Ezetimibe Administration
    Description
    Oxidative stress markers (membrane potential) was measured at baseline and after treatment by fluorometric techniques
    Time Frame
    Baseline, 4 weeks and 8 weeks
    Title
    Levels of Glutathione (GSH) Before and After Simvastatin/Ezetimibe Administration
    Description
    Oxidative stress markers (levels of glutathione (GSH)) was measured at baseline and after treatment by fluorometric techniques
    Time Frame
    Baseline, 4 weeks and 8 weeks
    Title
    Leukocyte Rolling Flux Before and After Simvastatin/Ezetimibe Administration
    Description
    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.
    Time Frame
    Baseline, 4 weeks and 8 weeks
    Title
    Leukocyte Adhesion Before and After Simvastatin/Ezetimibe Administration
    Description
    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.
    Time Frame
    Baseline, 4 weeks and 8 weeks
    Title
    Leukocyte Rolling Velocity Before and After Simvastatin/Ezetimibe Administration
    Description
    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.
    Time Frame
    Baseline, 4 weeks and 8 weeks
    Title
    Levels of Vascular Cell Adhesion Molecule 1 (VCAM-1) Before and After Simvastatin/Ezetimibe Administration
    Description
    The vascular cell adhesion molecule 1 (VCAM-1) was evaluated in serum by Luminex® 200™ system
    Time Frame
    Baseline, 4 weeks and 8 weeks
    Title
    Levels of Intercellular Adhesion Molecule 1 (ICAM-1) Before and After Simvastatin/Ezetimibe Administration
    Description
    The intercellular adhesion molecule 1 (ICAM-1) was evaluated in serum by Luminex® 200™ system
    Time Frame
    Baseline, 4 weeks and 8 weeks
    Title
    Levels of E-selectin Before and After Simvastatin/Ezetimibe Administration
    Description
    E-selectin was evaluated in serum by Luminex® 200™ system
    Time Frame
    Baseline, 4 weeks and 8 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Antonio Hernández, MD, Phd
    Organizational Affiliation
    FISABIO - University Hospital Dr Peset
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    20525999
    Citation
    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.
    Results Reference
    background
    PubMed Identifier
    21271793
    Citation
    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.
    Results Reference
    background
    PubMed Identifier
    15639688
    Citation
    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.
    Results Reference
    background

    Learn more about this trial

    Effects of Simvastatin and Ezetimibe on Cardiovascular Risk Markers in Patients With Dyslipidemia

    We'll reach out to this number within 24 hrs