Trial Outcomes & Findings for Merck Carotid Atherosclerosis Trial (MK-0000-111)(COMPLETED) (NCT NCT00804843)
NCT ID: NCT00804843
Last Updated: 2015-09-30
Results Overview
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).
COMPLETED
PHASE2
100 participants
At time of carotid endarterectomy (after 4 to 12 weeks of dosing)
2015-09-30
Participant Flow
Participant milestones
| Measure |
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
|
Statin 10 mg
Participants in Russia and Brasil will receive 10 mg Simvastatin. All other participants will receive 10 mg Atorvastatin.
|
|---|---|---|
|
Overall Study
STARTED
|
50
|
50
|
|
Overall Study
COMPLETED
|
40
|
43
|
|
Overall Study
NOT COMPLETED
|
10
|
7
|
Reasons for withdrawal
| Measure |
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
|
Statin 10 mg
Participants in Russia and Brasil will receive 10 mg Simvastatin. All other participants will receive 10 mg Atorvastatin.
|
|---|---|---|
|
Overall Study
Protocol Violation
|
1
|
0
|
|
Overall Study
Adverse Event
|
8
|
5
|
|
Overall Study
Withdrawal by Subject
|
1
|
2
|
Baseline Characteristics
Merck Carotid Atherosclerosis Trial (MK-0000-111)(COMPLETED)
Baseline characteristics by cohort
| Measure |
Statin 80 mg + Niacin ER
n=50 Participants
Participants in Russia and Brasil will receive 80 mg Simvastatin + niacin. All other participants will receive 80 mg Atorvastatin + niacin.
|
Statin 10 mg
n=50 Participants
Participants in Russia and Brasil will receive 10 mg Simvastatin. All other participants will receive 10 mg Atorvastatin.
|
Total
n=100 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
69.68 years
STANDARD_DEVIATION 9.42 • n=5 Participants
|
69.20 years
STANDARD_DEVIATION 8.63 • n=7 Participants
|
69.47 years
STANDARD_DEVIATION 8.99 • n=5 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
35 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
68 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: At time of carotid endarterectomy (after 4 to 12 weeks of dosing)Population: Only participants who completed the study, had evaluable plaque samples and were at least 80% compliant with dosing schedule were included in the 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).
Outcome measures
| Measure |
Statin 80 mg + Niacin Extended-release (ER)
n=36 Participants
Participants in Russia and Brasil will receive 80 mg Simvastatin + niacin. All other participants will receive 80 mg Atorvastatin + niacin
|
Statin 10 mg
n=34 Participants
Participants in Russia and Brasil will receive 10 mg Simvastatin. All other participants will receive 10 mg Atorvastatin.
|
|---|---|---|
|
Composite Score of Plaque Inflammation/Stability Gene Expression as Assayed by Ribonucleic Acid (RNA) Taqman Analysis
|
1.36 Cycle threshold (Ct)
Standard Deviation 1.17
|
0.82 Cycle threshold (Ct)
Standard Deviation 1.33
|
PRIMARY outcome
Timeframe: At time of carotid endarterectomy (after 4 to 12 weeks of dosing)Population: Only participants who completed the study, had evaluable plaque samples and were at least 80% compliant with dosing schedule were included in the analysis.
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.
Outcome measures
| Measure |
Statin 80 mg + Niacin Extended-release (ER)
n=36 Participants
Participants in Russia and Brasil will receive 80 mg Simvastatin + niacin. All other participants will receive 80 mg Atorvastatin + niacin
|
Statin 10 mg
n=34 Participants
Participants in Russia and Brasil will receive 10 mg Simvastatin. All other participants will receive 10 mg Atorvastatin.
|
|---|---|---|
|
Plaque Instability Protein Composite Score
|
-7.19 Score
Standard Deviation 10.45
|
-10.48 Score
Standard Deviation 11.70
|
PRIMARY outcome
Timeframe: At time of carotid endarterectomy (after 4 to 12 weeks of dosing)Population: 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.
Cholesterol ester was to be calculated by the following formula: Cholesterol Ester = Total Cholesterol - Free Cholesterol.
Outcome measures
Outcome data not reported
Adverse Events
Statin 80 mg + Niacin Extended-release (ER)
Statin 10 mg
Serious adverse events
| Measure |
Statin 80 mg + Niacin Extended-release (ER)
n=50 participants at risk
Participants in Russia and Brasil will receive 80 mg Simvastatin + niacin. All other participants will recieve 80 mg Atorvastatin + niacin
|
Statin 10 mg
n=50 participants at risk
Participants in Russia and Brasil will receive 10 mg Simvastatin. All other participants will
recieve 10 mg Atorvastatin.
|
|---|---|---|
|
Cardiac disorders
Atrial Fibrillation
|
2.0%
1/50 • Number of events 1
|
0.00%
0/50
|
|
Cardiac disorders
Coronary Artery Occlusion
|
2.0%
1/50 • Number of events 1
|
0.00%
0/50
|
|
Cardiac disorders
Myocardial Infarction
|
2.0%
1/50 • Number of events 1
|
2.0%
1/50 • Number of events 1
|
|
Eye disorders
Glaucoma
|
2.0%
1/50 • Number of events 1
|
0.00%
0/50
|
|
Gastrointestinal disorders
Gastritis
|
2.0%
1/50 • Number of events 1
|
0.00%
0/50
|
|
General disorders
Chest Pain
|
0.00%
0/50
|
2.0%
1/50 • Number of events 1
|
|
Infections and infestations
Bronchitis
|
0.00%
0/50
|
2.0%
1/50 • Number of events 1
|
|
Infections and infestations
Pyelonephritis Chronic
|
0.00%
0/50
|
2.0%
1/50 • Number of events 1
|
|
Injury, poisoning and procedural complications
Fall
|
2.0%
1/50 • Number of events 1
|
0.00%
0/50
|
|
Injury, poisoning and procedural complications
Overdose
|
2.0%
1/50 • Number of events 1
|
0.00%
0/50
|
|
Injury, poisoning and procedural complications
Pelvic Fracture
|
0.00%
0/50
|
2.0%
1/50 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
|
2.0%
1/50 • Number of events 1
|
0.00%
0/50
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric Cancer
|
0.00%
0/50
|
2.0%
1/50 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelofibrosis
|
0.00%
0/50
|
2.0%
1/50 • Number of events 1
|
|
Nervous system disorders
Cerebrovascular Accident
|
2.0%
1/50 • Number of events 1
|
0.00%
0/50
|
Other adverse events
| Measure |
Statin 80 mg + Niacin Extended-release (ER)
n=50 participants at risk
Participants in Russia and Brasil will receive 80 mg Simvastatin + niacin. All other participants will recieve 80 mg Atorvastatin + niacin
|
Statin 10 mg
n=50 participants at risk
Participants in Russia and Brasil will receive 10 mg Simvastatin. All other participants will
recieve 10 mg Atorvastatin.
|
|---|---|---|
|
Vascular disorders
Flushing
|
10.0%
5/50 • Number of events 5
|
4.0%
2/50 • Number of events 2
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER