Simvastatin With or Without Ezetimibe and Atherothrombotic Biomarker Assessment

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Michael Miller, University of Maryland
ClinicalTrials.gov Identifier:
NCT00819403
First received: January 7, 2009
Last updated: June 12, 2012
Last verified: June 2012
  Purpose

To determine whether the combination of ezetimibe and simvastatin improves biomarkers of atherothrombosis compared to simvastatin alone in patients with the metabolic syndrome.


Condition Intervention Phase
Metabolic Syndrome
Drug: simvastatin
Drug: ezetimibe/simvastatin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: The Effects of Ezetimibe/Simvastatin Versus Simvastatin Alone on Platelet and Inflammatory Biomarkers in Patients With the Metabolic Syndrome

Resource links provided by NLM:


Further study details as provided by University of Maryland:

Primary Outcome Measures:
  • To determine the ex vivo effects of treatment with Vytorin versus Zocor for 6 weeks on platelet alpha thrombin PAR-1 receptor expression. The flow cytometry measurements will be done by the central core lab in a blinded fashion. [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • We will compare how treatment with Vytorin versus Zocor for 6 weeks will affect platelet activity, and inflammatory biomarkers as secondary endpoints for the study. [ Time Frame: 3 mo ] [ Designated as safety issue: No ]

Enrollment: 15
Study Start Date: January 2009
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: simvastatin
Simvastatin 40 mg daily
Drug: simvastatin
Subjects will receive 6 weeks of simvastatin 40 mg, after which atherothrombotic biomarker assessment will be studied.
Other Name: zocor
Active Comparator: simvastatin/ezetimibe
Subjects will receive 6 weeks of ezetimibe/simvastatin 10/40 mg, after which atherothrombotic biomarker assessment will be studied.
Drug: ezetimibe/simvastatin
Subjects will receive 6 weeks of simvastatin 40 mg, after which atherothrombotic biomarker assessment will be studied.

Detailed Description:
  1. To assess the ex vivo effects of ezetimibe/simvastatin (E/S) (Vytorin 10/40mg) and simvastatin (S) (Zocor 40mg) on platelet and inflammation biomarkers in patients with documented metabolic syndrome.
  2. To compare platelet-related effects including PAR-1 receptor inhibition of E/S with those of the established anti-platelet agents including aspirin, clopidogrel, intravenous and oral glycoprotein IIb/IIIa inhibitors.
  3. To determine whether the addition of ezetimibe will yield extra protection beyond lipid modulation in the reduction of inflammation and platelet activation.
  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Men and women greater than or equal to 21 years of age
  2. Diagnosis of metabolic syndrome. We defined the presence of metabolic syndrome based on the US National Cholesterol Education Program's Adult Treatment Panel III guidelines. Specifically, metabolic syndrome will be diagnosed and documented when 3 of the following 5 characteristics will be present:

    • abdominal obesity, given as waist circumference for men > 102 cm, and for women > 88 cm
    • triglycerides > 150 mg/dL
    • HDL cholesterol < 40 mg/dL for men, and < 50 mg/dL for women
    • blood pressure > 130/85 mm Hg
    • fasting glucose > 100 mg/dL

Exclusion Criteria:

  1. Patients will be excluded for a history of bleeding diathesis
  2. drug or alcohol abuse
  3. prothrombin time greater than 1.5 times control
  4. platelet count < 100,000/mm3
  5. hematocrit < 25%
  6. creatinine > 4.0 mg/dl
  7. surgery or angioplasty performed within 3 months or planned for the future
  8. history of gastrointestinal or other bleeding
  9. history of drug-induced disorders
  10. trauma, cancer, rheumatic diseases, coronary artery disease or stroke
  11. Patients participating in other investigational drug trials within one month of completion will be also excluded
  12. Patients treated with intravenous platelet glycoprotein IIb/IIIa inhibitors or thienopyridines, within past 6 months
  13. Patients treated with statins or aspirin within past four weeks
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00819403

Locations
United States, Maryland
University of Maryland Medical Center
Baltimore, Maryland, United States, 21202
VA Maryland Health Care System
Baltimore, Maryland, United States, 21201
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
University of Maryland
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: MICHAEL MILLER, MD University of Maryland
Study Director: VICTOR L. Serebruany, MD, PhD President, HeartDrug Research LLC
  More Information

No publications provided

Responsible Party: Michael Miller, Dr., University of Maryland
ClinicalTrials.gov Identifier: NCT00819403     History of Changes
Other Study ID Numbers: HP-00040970, MSP-JV IISP #32031
Study First Received: January 7, 2009
Last Updated: June 12, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by University of Maryland:
triglycerides
hypertension
low hdl
obesity

Additional relevant MeSH terms:
Metabolic Syndrome X
Syndrome
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Disease
Pathologic Processes
Simvastatin
Ezetimibe
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 22, 2014