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

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

Official Title
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A Randomized Clinical Trial to Evaluate the Effects of High Dose Statin and Niacin Therapy on Excised Plaque Biomarkers in Patients Undergoing Carotid Endarterectomy (CEA)

Conditions
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Carotid Atherosclerosis

Intervention / Treatment
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* Drug: Atorvastatin/niacin extended-release
* Drug: Atorvastatin
* Drug: Simvastatin
* Drug: Simvastatin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Statin 80 mg + Niacin extended-release (ER)<br>Participants in Russia and Brasil will receive 80 mg Simvastatin + niacin. All other participants will receive 80 mg Atorvastatin + niacin. | Drug: Atorvastatin/niacin extended-release<br>* 80 mg tablet atorvastatin once daily, 10 mg tablet placebo to atorvastatin once daily, and niacin extended-release tablet starting at 500 mg daily and titrating to 2g daily. Treatment will be from 4 to 12 weeks.<br>* Other names: Lipitor, Niaspan;Drug: Simvastatin<br>* (Russia and Brazil) 80 mg tablet simvastatin once daily, 10 mg tablet placebo to simvastatin once daily, and niacin extended-release tablet starting at 500 mg daily and titrating to 2g daily. Treatment will be from 4 to 12 weeks.<br>* Other names: Zocor;|
| Active Comparator: Statin 10 mg<br>Participants in Russia and Brasil will receive 10 mg Simvastatin. All other participants will receive 10 mg Atorvastatin. | Drug: Atorvastatin<br>* 10 mg tablet atorvastatin once daily, 80 mg tablet placebo to atorvastatin once daily, and placebo to niacin extended-release tablet starting at 500 mg daily and titrating to 2g daily. Treatment will be from 4 to 12 weeks.<br>* Other names: Lipitor;Drug: Simvastatin<br>* (Russia and Brazil) 10 mg tablet simvastatin once daily, 80 mg tablet placebo to simvastatin once daily, and placebo to niacin extended-release tablet starting at 500 mg daily and titrating to 2g daily. Treatment will be from 4 to 12 weeks.<br>* Other names: Zocor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Score of Plaque Inflammation/Stability Gene Expression as Assayed by Ribonucleic Acid (RNA) Taqman Analysis | 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). | At time of carotid endarterectomy (after 4 to 12 weeks of dosing) | 
| Plaque Instability Protein Composite Score | 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. | At time of carotid endarterectomy (after 4 to 12 weeks of dosing) | 
| Total Cholesterol and Free Cholesterol Measured by Enzymatic Chromogenic Assay | Cholesterol ester was to be calculated by the following formula: Cholesterol Ester = Total Cholesterol - Free Cholesterol. | At time of carotid endarterectomy (after 4 to 12 weeks of dosing) |