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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00804843
First received: December 8, 2008
Last updated: October 24, 2013
Last verified: October 2013
  Purpose

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


Condition Intervention Phase
Carotid Atherosclerosis
Drug: Atorvastatin/niacin extended-release
Drug: Atorvastatin
Drug: Simvastatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Composite Score of Plaque Inflammation/Stability Gene Expression as Assayed by Ribonucleic Acid (RNA) Taqman Analysis [ Time Frame: At time of carotid endarterectomy (after 4 to 12 weeks of dosing) ] [ Designated as safety issue: No ]
    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).

  • Plaque Instability Protein Composite Score [ Time Frame: At time of carotid endarterectomy (after 4 to 12 weeks of dosing) ] [ Designated as safety issue: No ]
    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.

  • Total Cholesterol and Free Cholesterol Measured by Enzymatic Chromogenic Assay [ Time Frame: At time of carotid endarterectomy (after 4 to 12 weeks of dosing) ] [ Designated as safety issue: No ]
    Cholesterol ester was to be calculated by the following formula: Cholesterol Ester = Total Cholesterol - Free Cholesterol.


Enrollment: 100
Study Start Date: April 2009
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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: 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 Name: Lipitor
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 Name: Zocor

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00804843

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00804843     History of Changes
Other Study ID Numbers: 0000-111, 2008_598
Study First Received: December 8, 2008
Results First Received: December 21, 2011
Last Updated: October 24, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Atherosclerosis
Carotid Artery Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Niacin
Simvastatin
Atorvastatin
Nicotinic Acids
Niacinamide
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents

ClinicalTrials.gov processed this record on April 17, 2014