Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Antiplatelet and Anti-inflammatory Effects of Statins and Ezetimibe

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00474123
Recruitment Status : Completed
First Posted : May 16, 2007
Results First Posted : July 14, 2010
Last Update Posted : July 14, 2010
Sponsor:
Information provided by:
University of Sao Paulo

Tracking Information
First Submitted Date  ICMJE May 15, 2007
First Posted Date  ICMJE May 16, 2007
Results First Submitted Date  ICMJE January 8, 2010
Results First Posted Date  ICMJE July 14, 2010
Last Update Posted Date July 14, 2010
Study Start Date  ICMJE January 2006
Actual Primary Completion Date January 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 18, 2010)
  • C-reactive Protein [ Time Frame: Change from baseline at 6 weeks ]
    Serum was separated by centrifugation from the blood samples. For high-sensitivity C-Reactive Protein measurement, whole venous blood was collected in tubes without anticoagulant and centrifuged at room temperature. Serum C-Reactive Protein was assessed with a high-sensitivity, latex microparticle-enhanced immunoturbidimetric assay (Behring Nephelometer Analyzer System; Behring Diagnostics, Somerville, NJ).
  • Oxidized Low-Density Lipoprotein Cholesterol [ Time Frame: Change from baseline at 6 weeks ]
    Serum samples were stored at -70°C and were determined simultaneously by ELISA in order to avoid variation of assay conditions. Commercial ELISA assays detecting oxLDL (Mercodia, USA) were applied.
  • Platelet Function Analyzer [PFA]-100 [ Time Frame: Change from baseline at 6 weeks ]
    Samples were collected in 3.8% sodium citrate (buffered, pH 5.5, Vacutainer, Becton Dickinson, Plymouth, UK) for platelet function tests. Platelet function assays were processed within 2 hours of blood collection. The PFA-100 records the closure time (CT), witch means the time in seconds (s) from the start of the test until the platelet plug occludes the aperture.
  • Monocyte Chemoattractant Protein (MCP)-1 [ Time Frame: Change from baseline at 6 weeks ]
    Serum samples were stored at -70°C and were determined simultaneously by ELISA in order to avoid variation of assay conditions. Commercial ELISA assays detecting MCP-1/ICAM-1 (R&D Systems, Europe, Abingdon, UK).
  • Soluble Intercellular Adhesion Molecule (sICAM)-1 [ Time Frame: Change from baseline at 6 weeks ]
    serum samples were stored at -70°C and were determined simultaneously by ELISA in order to avoid variation of assay conditions. Commercial ELISA assays detecting MCP-1/ICAM-1 (R&D Systems, Europe, Abingdon, UK)
  • Soluble CD40 Ligand [ Time Frame: Fasting venous blood samples were drawn immediately after randomization and after at the conclusions of the six weeks study period. ]
    A commercial ELISA assay detecting sCD40L (R&D Systems, USA) was applied. Detection limits and intra-assay variability was respectively, as follows: sCD-40L 15.6 pg/mL (intra-assay variability not available).
  • Interleukin-6 [ Time Frame: Fasting venous blood samples were drawn immediately after randomization and after at the conclusions of the six weeks study period. ]
    A commercial ELISA assay detecting IL-6 (Siemens, USA) was applied.
Original Primary Outcome Measures  ICMJE
 (submitted: May 15, 2007)
Inflammation will be denoted by measuring the following markers: CRP, interleukins, MCP-1, sICAM-1 and oxLDL. Progenitor endothelial cells are also determined. [ Time Frame: 6 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 18, 2010)
  • LDL Cholesterol [ Time Frame: Fasting venous blood samples were drawn immediately after randomization and at the conclusions of the six week study period. ]
  • Triglyceride [ Time Frame: Fasting venous blood samples were drawn immediately after randomization and at the conclusions of the six week study period. ]
  • Endothelial Progenitor Cells [ Time Frame: Fasting venous blood samples were drawn immediately after randomization and at the conclusions of the six week study period. ]
    Endothelial progenitor cells were evaluated by flow cytometry. Selected cells were positive for CD31, CD34 and VEGFR receptors.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Antiplatelet and Anti-inflammatory Effects of Statins and Ezetimibe
Official Title  ICMJE Comparison of Antiplatelet and Anti-inflammatory Effects of High Dose Statin Monotherapy Versus Moderate Dose Statin Plus Ezetimibe
Brief Summary

Among patients with stable coronary artery disease (CAD), it is not clear if the pleiotropic effects of cholesterol reduction differ between high-dose simvastatin alone and combined ezetimibe/simvastatin.

The investigators sought to compare the anti-inflammatory and anti-platelet effects of ezetimibe 10 mg / simvastatin 20 mg (E10/S20) to simvastatin 80 mg (S80).

Detailed Description

Introduction

Among patients with coronary artery disease (CAD), a robust evidence base supports the beneficial effects of statin therapy on mortality and other adverse cardiovascular outcomes . Recently, two large trials , have demonstrated that compared to standard dose statin therapy, high statin doses reduced Low-density lipoprotein-C (LDL-C) to extremely low levels and decreased coronary events, even in patients with normal levels of Low-density lipoprotein-C (LDL-C). Subsequently, recent guidelines have suggested an Low-density lipoprotein-C (LDL-C) treatment goal of <70 mg/dL in patients with coronary artery disease (CAD). Achieving such low Low-density lipoprotein-C (LDL-C) levels frequently demands an intensive Low-density lipoprotein-C (LDL-C) reduction, often above 50%. Ezetimibe, an intestinal cholesterol absorption inhibitor, can be used as an additional therapy if statin monotherapy fails to reduce Low-density lipoprotein-C (LDL-C) below the treatment goal.

Furthermore, anti-inflammatory and antithrombotic pleiotropic effects of statins might explain, at least in part, the large benefits demonstrated in randomized trials , . For example, in hypercholesterolemic patients treated with statins, a decrease in inflammation-associated markers such as the C-reactive protein (CRP) has been described , although it is debated whether this effect is clearly independent of Low-density lipoprotein-C (LDL-C).

Moreover, although inhibition of platelets by statin therapy is a well established effect , , it has not yet been clarified whether platelet inhibition by statin therapy depends on the reduction of Low-density lipoprotein-C (LDL-C) or on the inhibition of intracellular signal pathways accompanied by disaggregating effects.

Two alternative pharmacologic strategies are equally effective in reducing Low-density lipoprotein-C (LDL-C): high-dose statin alone and combined treatment with ezetimibe plus moderate-dose statin . It is not known whether these two strategies have different cholesterol-independent pleiotropic effects on inflammation and platelets. We therefore compared the anti-inflammatory and antiplatelet effects of two intensive pharmacologic strategies to reduce cholesterol: 80 mg of simvastatin (S80) versus 10 mg ezetimibe/ 20 mg of simvastatin (E10/S20). Anti-inflammatory effects were assessed by performing serial measurements of the following biomarkers: C-Reactive Protein (CRP), monocyte chemoattractant protein (MCP)-1, oxidized Low-density lipoprotein-C (oxLDL), soluble intercellular adhesion molecule (sICAM)-1. Platelet aggregation was also compared between the two strategies.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Stable Angina
Intervention  ICMJE
  • Drug: Simvastatin 80 mg/day for 6 weeks
    Simvastatin 80 mg/day, single dose, for 6 weeks.
    Other Name: Simvastatin 80 mg (Zocor)
  • Drug: Ezetimibe 10 mg / Simvastatin 20 mg

    Ezetimibe 10 mg / Simvastatin 20 mg

    Patients were treated with daily Ezetimibe 10 mg / Simvastatin 20 mg for 6 weeks

    Other Name: Vytorin
Study Arms  ICMJE
  • Active Comparator: Simvastatin 80 mg
    Patients were treated with simvastatin 80 mg for 6 weeks
    Intervention: Drug: Simvastatin 80 mg/day for 6 weeks
  • Active Comparator: Ezetimibe 10 mg / Simvastatin 20 mg
    Patients were treated with daily Ezetimibe 10 mg / Simvastatin 20 mg for 6 weeks
    Intervention: Drug: Ezetimibe 10 mg / Simvastatin 20 mg
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 18, 2010)
78
Original Estimated Enrollment  ICMJE
 (submitted: May 15, 2007)
80
Actual Study Completion Date  ICMJE August 2009
Actual Primary Completion Date January 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Stable angina
  • Low-density lipoprotein (LDL) cholesterol 70-160 mg/dl

Exclusion Criteria:

  • Renal failure
  • Age>80
  • Simvastatin current treatment>20mg
  • Hepatic disease
  • Inflammatory diseases
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00474123
Other Study ID Numbers  ICMJE 893/05
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party São Paulo Research Foundation (FAPESP)
Study Sponsor  ICMJE University of Sao Paulo
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: CARLOS V SERRANO, PHD Heart Institute (InCor) HOSPITAL DAS CLINICAS DA FACULDADE DE MEDICINA DA UNIVERSIDADE DE SAO PAULO (HCFMUSP)
PRS Account University of Sao Paulo
Verification Date February 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP