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

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)

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

Study Overview

• Status: Completed
• Conditions: Carotid Atherosclerosis
• Intervention / Treatment: Drug: Atorvastatin/niacin extended-release; Drug: Simvastatin; Drug: Simvastatin; Drug: Atorvastatin

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Statin 80 mg + Niacin extended-release (ER); 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; 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.; Other Names: Lipitor, Niaspan; Drug: Simvastatin; (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.; Other Names: Zocor; Drug: Simvastatin; (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.; Other Names: Zocor
Active Comparator: Statin 10 mg; Participants in Russia and Brasil will receive 10 mg Simvastatin. All other participants will receive 10 mg Atorvastatin.	Drug: Simvastatin; (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.; Other Names: Zocor; Drug: Simvastatin; (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.; Other Names: Zocor; Drug: Atorvastatin; 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.; Other Names: Lipitor

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: December 8, 2008
• First Submitted That Met QC Criteria: December 8, 2008
• First Posted (Estimate): December 9, 2008

Study Record Updates

• Last Update Posted (Estimate): September 30, 2015
• Last Update Submitted That Met QC Criteria: September 28, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Carotid Artery Diseases; Atherosclerosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Antimetabolites; Micronutrients; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Vitamins; Vitamin B Complex; Atorvastatin; Simvastatin; Niacin
• Other Study ID Numbers: 0000-111; 2008_598 (Merck Study Number)