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)
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 100
- Primary Endpoint
- Plaque Instability Protein Composite Score
Study Overview
Brief Summary
This study will examine the effect of statin and niacin therapy on carotid plaque biomarkers
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 90 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
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.
Intervention: Atorvastatin/niacin extended-release (Drug)
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.
Intervention: Simvastatin (Drug)
Statin 10 mg
Participants in Russia and Brasil will receive 10 mg Simvastatin. All other participants will receive 10 mg Atorvastatin.
Intervention: Atorvastatin (Drug)
Statin 10 mg
Participants in Russia and Brasil will receive 10 mg Simvastatin. All other participants will receive 10 mg Atorvastatin.
Intervention: Simvastatin (Drug)
Outcomes
Primary Outcomes
Plaque Instability Protein Composite Score
Time Frame: 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
Time Frame: 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
Time Frame: 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.
Secondary Outcomes
No secondary outcomes reported