Clinical trial NCT00819403: Simvastatin With or Without Ezetimibe and Atherothrombotic Biomarker Assessment
Official title: The Effects of Ezetimibe/Simvastatin Versus Simvastatin Alone on Platelet and Inflammatory Biomarkers in Patients With the Metabolic Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Metabolic Syndrome
Keywords: triglycerides
hypertension
low hdl
obesity
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2009-01-09
Enrollment: 15
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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

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 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

Primary outcomes:
measure: Ex Vivo Effects of Treatment With Vytorin Versus Zocor for 6 Weeks on Platelet Alpha Thrombin PAR-1 Receptor Expression
timeFrame: 6 weeks
Secondary outcomes:
measure: Biomarkers of Inflammation
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: VA Maryland Health Care System
state: Maryland
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
Study officials:
affiliation: University of Maryland, College Park
name: MICHAEL MILLER, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: President, HeartDrug Research LLC
name: VICTOR L. Serebruany, MD, PhD
role: STUDY_DIRECTOR
References: