Simvastatin With or Without Ezetimibe and Atherothrombotic Biomarker Assessment

Phase 4

Completed

• Conditions: Metabolic Syndrome
• Interventions: Drug: ezetimibe/simvastatin; Drug: simvastatin

• Registration Number: NCT00819403
• Lead Sponsor: University of Maryland, Baltimore

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.

Study Timeline

• Study Start: 2009-01
• Study First Submitted: 2009-01-07
• Study First Submitted QC: 2009-01-08
• Study First Posted: 2009-01-09
• Primary Completion: 2011-11
• Study Completion: 2011-11
• Results First Submitted: 2013-02-27
• Results First Submitted QC: 2014-12-10
• Results First Posted: 2014-12-18
• Status Verified: 2020-01
• Last Update Submitted: 2020-01-10
• Last Update Posted: 2020-01-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Ex Vivo Effects of Treatment With Vytorin Versus Zocor for 6 Weeks on Platelet Alpha Thrombin PAR-1 Receptor Expression	6 weeks	Measured using whole blood flow cytometry

Secondary Outcome Measures

Name	Time	Method
Biomarkers of Inflammation	6 weeks

Trial Locations

Locations (3)

VA Maryland Health Care System; 🇺🇸 Baltimore, Maryland, United States

University of Maryland Medical Center; 🇺🇸 Baltimore, Maryland, United States

Johns Hopkins Hospital; 🇺🇸 Baltimore, Maryland, United States