Simvastatin With or Without Ezetimibe and Atherothrombotic Biomarker Assessment

University of Maryland Baltimore (UMB)

Status and phase: Completed; Phase 4

Conditions: Metabolic Syndrome

Treatments: Drug: simvastatin; Drug: ezetimibe/simvastatin

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00819403

MSP-JV IISP #32031

HP-00040970

Details and patient eligibility

About

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

Full 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.

Enrollment: 15 patients

Sex: All

Ages: 21+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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15 participants in 2 patient groups

simvastatin

Active Comparator group

Description:

Simvastatin 40 mg daily

Treatment:

Drug: simvastatin

simvastatin/ezetimibe

Active Comparator group

Description:

Subjects will receive 6 weeks of ezetimibe/simvastatin 10/40 mg, after which atherothrombotic biomarker assessment will be studied.

Treatment:

Drug: ezetimibe/simvastatin