Merck Carotid Atherosclerosis Trial (MK-0000-111)(COMPLETED)

Phase 2

Completed

Conditions: Carotid Atherosclerosis

Interventions: Drug: Atorvastatin/niacin extended-release
Drug: Atorvastatin
Drug: Simvastatin

Registration Number: NCT00804843

Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary: This study will examine the effect of statin and niacin therapy on carotid plaque biomarkers

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 100

Inclusion Criteria

Patient is diagnosed with carotid stenosis AND is scheduled to undergo carotid endarterectomy
Female patients of reproductive potential must abstain from sex or use an acceptable method of birth control through out the study

Exclusion Criteria

Patient must undergo CEA less than 4 weeks after entering study
Patient has recent history of acute coronary syndrome
Patient has has coronary artery bypass graft surgery within 30 days of study start
Patient has thyroid disease that has not been treated for more than 6 weeks
Patient has donated blood within 8 weeks of study start
Patient has poorly controlled diabetes mellitis
Patient has human immunodeficiency virus (HIV) or Hepatitis B or C
Patient is taking warfarin or other anticoagulants
Patient is taking hormone replacement therapy

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Statin 80 mg + Niacin extended-release (ER)	Atorvastatin/niacin extended-release	Participants in Russia and Brasil will receive 80 mg Simvastatin + niacin. All other participants will receive 80 mg Atorvastatin + niacin.
Statin 10 mg	Simvastatin	Participants in Russia and Brasil will receive 10 mg Simvastatin. All other participants will receive 10 mg Atorvastatin.
Statin 80 mg + Niacin extended-release (ER)	Simvastatin	Participants in Russia and Brasil will receive 80 mg Simvastatin + niacin. All other participants will receive 80 mg Atorvastatin + niacin.
Statin 10 mg	Atorvastatin	Participants in Russia and Brasil will receive 10 mg Simvastatin. All other participants will receive 10 mg Atorvastatin.

Primary Outcome Measures

Name	Time	Method
Plaque Instability Protein Composite Score	At time of carotid endarterectomy (after 4 to 12 weeks of dosing)	Each excised plaque was analyzed using an assay of 20 proteins that reflect plaque composition and inflammation. Each protein was assigned scaled signs, with a lower (negative) sign associated with plaque stability and a higher (positive) sign associated with plaque inflammation/instability. The Composite Score was the average amounts of all the 20 proteins with their associated signs. A higher Composite Score is associated with more plaque instability.
Composite Score of Plaque Inflammation/Stability Gene Expression as Assayed by Ribonucleic Acid (RNA) Taqman Analysis	At time of carotid endarterectomy (after 4 to 12 weeks of dosing)	Excised carotid plaques were evaluated for the gene expression of 60 biomarkers associated with inflammation ("Hot" biomarkers) \& 25 biomarkers associated with stability ("Cold" biomarkers). Each biomarker was assayed using a quantitative polymerase chain reaction method and results were reported as a Cycle Threshold, (Ct). A Composite Score was calculated by averaging the Ct for each of the 25 "cold" genes, and subtracting the average Ct for the 60 "hot" genes. A higher composite score was associated with greater inflammation and a lower score was associated with stability (non-inflamed).
Total Cholesterol and Free Cholesterol Measured by Enzymatic Chromogenic Assay	At time of carotid endarterectomy (after 4 to 12 weeks of dosing)	Cholesterol ester was to be calculated by the following formula: Cholesterol Ester = Total Cholesterol - Free Cholesterol.