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| ID | Type | Description | Link |
|---|---|---|---|
| 2008_598 | Other Identifier | Merck Study Number |
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This study will examine the effect of statin and niacin therapy on carotid plaque biomarkers
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Statin 80 mg + Niacin extended-release (ER) | Experimental | Participants in Russia and Brasil will receive 80 mg Simvastatin + niacin. All other participants will receive 80 mg Atorvastatin + niacin. |
|
| Statin 10 mg | Active Comparator | Participants in Russia and Brasil will receive 10 mg Simvastatin. All other participants will receive 10 mg Atorvastatin. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atorvastatin/niacin extended-release | Drug | 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. |
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Merck Sharp & Dohme LLC | Study Director |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | Statin 10 mg | Participants in Russia and Brasil will receive 10 mg Simvastatin. All other participants will receive 10 mg Atorvastatin. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Statin 80 mg + Niacin ER | Participants in Russia and Brasil will receive 80 mg Simvastatin + niacin. All other participants will receive 80 mg Atorvastatin + niacin. |
| BG001 | Statin 10 mg |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | Only participants who completed the study, had evaluable plaque samples and were at least 80% compliant with dosing schedule were included in the analysis. | Posted | Mean | Standard Deviation | Cycle threshold (Ct) | At time of carotid endarterectomy (after 4 to 12 weeks of dosing) |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Statin 80 mg + Niacin Extended-release (ER) | Participants in Russia and Brasil will receive 80 mg Simvastatin + niacin. All other participants will recieve 80 mg Atorvastatin + niacin |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial Fibrillation | Cardiac disorders | MedDRA (14.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Flushing | Vascular disorders | MedDRA (14.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D002340 | Carotid Artery Diseases |
| ID | Term |
|---|---|
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D000069059 | Atorvastatin |
| D009525 | Niacin |
| D019821 | Simvastatin |
| ID | Term |
|---|---|
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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|
| Atorvastatin | Drug | 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. |
|
|
| Simvastatin | Drug | (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. |
|
|
| Simvastatin | Drug | (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. |
|
|
| Withdrawal by Subject |
|
Participants in Russia and Brasil will receive 10 mg Simvastatin. All other participants will receive 10 mg Atorvastatin.
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| 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 |
| OG001 | Statin 10 mg | Participants in Russia and Brasil will receive 10 mg Simvastatin. All other participants will receive 10 mg Atorvastatin. |
|
|
|
| Primary | 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. | Only participants who completed the study, had evaluable plaque samples and were at least 80% compliant with dosing schedule were included in the analysis. | Posted | Mean | Standard Deviation | Score | At time of carotid endarterectomy (after 4 to 12 weeks of dosing) |
|
|
|
|
| Primary | 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. | Only participants who completed the study, had evaluable plaque samples and were at least 80% compliant with dosing schedule were to be included in the analysis. This was not performed due to technical concerns. Instead, the cholesterol content determination, if performed, will use mass spectrometry approach and would be an exploratory objective. | Posted | At time of carotid endarterectomy (after 4 to 12 weeks of dosing) |
|
|
| 9 |
| 50 |
| 5 |
| 50 |
| EG001 | Statin 10 mg | Participants in Russia and Brasil will receive 10 mg Simvastatin. All other participants will recieve 10 mg Atorvastatin. | 7 | 50 | 2 | 50 |
| Coronary Artery Occlusion | Cardiac disorders | MedDRA (14.0) | Systematic Assessment |
|
| Myocardial Infarction | Cardiac disorders | MedDRA (14.0) | Systematic Assessment |
|
| Glaucoma | Eye disorders | MedDRA (14.0) | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
|
| Chest Pain | General disorders | MedDRA (14.0) | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Pyelonephritis Chronic | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA (14.0) | Systematic Assessment |
|
| Overdose | Injury, poisoning and procedural complications | MedDRA (14.0) | Systematic Assessment |
|
| Pelvic Fracture | Injury, poisoning and procedural complications | MedDRA (14.0) | Systematic Assessment |
|
| Rhabdomyolysis | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
| Gastric Cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (14.0) | Systematic Assessment |
|
| Myelofibrosis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (14.0) | Systematic Assessment |
|
| Cerebrovascular Accident | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
|
Publications derived from the study should include input from the investigator(s) and SPONSOR. After to the multicenter publication, or 24 months after completion of the study, whichever comes first, an investigator may publish the results for the study site independently. The SPONSOR must have the opportunity to review all proposed publications 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission.
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D006538 |
| Heptanoic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D009539 | Nicotinic Acids |
| D000147 | Acids, Heterocyclic |
| D011725 | Pyridines |
| D008148 | Lovastatin |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |