- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00862251
Ezetimibe/Simvastatin (MK-0653A) Versus Rosuvastatin Versus Doubling Statin Dose in Participants With Cardiovascular Disease and Diabetes Mellitus (MK-0653A-133)(COMPLETED)
February 7, 2022 updated by: Organon and Co
A Randomized, Double-Blind, Active-Controlled Study of Patients With Cardiovascular Disease and Diabetes Mellitus Not Adequately Controlled With Simvastatin or Atorvastatin: Comparison of Switching to Combination Tablet Ezetimibe/Simvastatin Versus Switching to Rosuvastatin or Doubling the Statin Dose
The purpose of this study is to determine the efficacy of switching to a combination tablet ezetimibe/simvastatin (10mg/20mg) versus rosuvastatin (10 mg) versus doubling the statin dose in those patients who have cardiovascular disease and diabetes mellitus not adequately controlled on simvastatin 20 mg or atorvastatin 10 mg.
Study Overview
Status
Completed
Conditions
Study Type
Interventional
Enrollment (Actual)
808
Phase
- Phase 3
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years to 77 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Patient has not taken common statins or ezetimibe within 6 weeks of study screening or patient is currently taking a daily dose of the following statins for 6 weeks prior to study screening: simvastatin, atorvastatin, pravastatin, fluvastatin, ezetimibe, lovastatin, or ezetimibe + fluvastatin
- Patient is willing to go on a cholesterol and glucose lowering diet for the duration of the study
- Patient is willing to remain abstinent or use birth control for the duration of the study
- Patient has Diabetes Mellitus with cardiovascular disease
Exclusion Criteria:
- Patient has sensitivity to certain common statin drugs
- Patient is Asian and would not be able to start taking the higher doses of rosuvastatin necessary for the study design
- Patient consumes more than 2 alcoholic drinks per day
- Patient is pregnant or breast-feeding
- Patient has been treated with other investigational drugs within 30 days of first visit
- Patient is currently on prohibited doses of the following statin drugs: rosuvastatin, simvastatin, atorvastatin, and pravastatin
- Patient has congestive heart failure
- Patient has uncontrolled high blood pressure
- Patient has kidney disease
- Patient has uncontrolled endocrine or metabolic disease which are known to possibly increase blood lipoproteins
- Patient has diabetes mellitus that is not well controlled
- Patient is human immunodeficiency virus (HIV) positive
- Patient is currently taking medications that inhibit Cytochrome P450 3A4 (CYP3A4)
- Patient is currently taking therapies that would increase the risk of muscle weakness
- Patient has been taking certain over- the-counter lipid-lowering agents within 6 weeks prior to visit 1
- Patient is currently taking psyllium or other fiber-based laxatives
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Rosuvastatin
|
All patients will take atorvastatin 10 mg tablets OR simvastatin 20 mg tablets, taken once daily in a 6-week screening/stabilization period prior to randomization.
Other Names:
rosuvastatin 10 mg tablets, taken once daily for six weeks.
Other Names:
|
Experimental: Ezetimibe/simvastatin
|
ezetimibe/simvastatin 10/20 mg tablets, taken once daily for six weeks.
Other Names:
All patients will take atorvastatin 10 mg tablets OR simvastatin 20 mg tablets, taken once daily in a 6-week screening/stabilization period prior to randomization.
Other Names:
|
Active Comparator: Doubling statin dose
|
All patients will take atorvastatin 10 mg tablets OR simvastatin 20 mg tablets, taken once daily in a 6-week screening/stabilization period prior to randomization.
Other Names:
simvastatin 40 mg or atorvastatin 20 mg tablets, taken once daily for six weeks.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) After Switching to Treatment With Ezetimibe/Simvastatin vs Doubling the Dose of Statin (Simvastatin or Atorvastatin).
Time Frame: Baseline and Week 6
|
Baseline and Week 6
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
In Participants Treated With Simvastatin at Baseline, Percent Change From Baseline in LDL-C After Switching to Treatment With Ezetimibe/Simvastatin vs Doubling the Dose of Simvastatin
Time Frame: Baseline and Week 6
|
Baseline and Week 6
|
In Participants Treated With Atorvastatin at Baseline, Percent Change From Baseline in LDL-C After Switching to Treatment With Ezetimibe/Simvastatin vs Doubling the Dose of Atorvastatin
Time Frame: Baseline and Week 6
|
Baseline and Week 6
|
Percent Change From Baseline in LDL-C After Switching to Treatment With Ezetimibe/Simvastatin vs Switching Treatment to Rosuvastatin
Time Frame: Baseline and Week 6
|
Baseline and Week 6
|
Number of Participants Who Reached the Target LDL-Cholesterol Level of < 70 mg/dL (1.81 mmol/L)
Time Frame: Week 6
|
Week 6
|
In Participants Treated With Simvastatin at Baseline, Number of Participants Who Reached the Target LDL-Cholesterol Level of < 70 mg/dL (1.81 mmol/L)
Time Frame: Week 6
|
Week 6
|
In Participants Treated With Atorvastatin at Baseline, Number of Participants Who Reached the Target LDL-Cholesterol Level of < 70 mg/dL (1.81 mmol/L)
Time Frame: Week 6
|
Week 6
|
Percent Change From Baseline in Total Cholesterol (TC)
Time Frame: Baseline and Week 6
|
Baseline and Week 6
|
Percent Change From Baseline in Triglycerides
Time Frame: Baseline and Week 6
|
Baseline and Week 6
|
Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C)
Time Frame: Baseline and Week 6
|
Baseline and Week 6
|
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)
Time Frame: Baseline and Week 6
|
Baseline and Week 6
|
Percent Change From Baseline in LDL-C/HDL-C Ratio
Time Frame: Baseline and Week 6
|
Baseline and Week 6
|
Percent Change From Baseline in TC/HDL-C Ratio
Time Frame: Baseline and Week 6
|
Baseline and Week 6
|
Percent Change From Baseline in Non-HDL-C/HDL-C Ratio
Time Frame: Baseline and Week 6
|
Baseline and Week 6
|
Percent Change From Baseline in Apolipoprotein B (Apo B)
Time Frame: Baseline and Week 6
|
Baseline and Week 6
|
Percent Change From Baseline Apolipoprotein A-I (Apo A-I)
Time Frame: Baseline and Week 6
|
Baseline and Week 6
|
Percent Change From Baseline in Apo B/Apo A-I Ratio
Time Frame: Baseline and Week 6
|
Baseline and Week 6
|
Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP)
Time Frame: Baseline and Week 6
|
Baseline and Week 6
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Le NA, Tomassini JE, Tershakovec AM, Neff DR, Wilson PW. Effect of Switching From Statin Monotherapy to Ezetimibe/Simvastatin Combination Therapy Compared With Other Intensified Lipid-Lowering Strategies on Lipoprotein Subclasses in Diabetic Patients With Symptomatic Cardiovascular Disease. J Am Heart Assoc. 2015 Oct 20;4(10):e001675. doi: 10.1161/JAHA.114.001675.
- Rosen JB, Jimenez JG, Pirags V, Vides H, Massaad R, Hanson ME, Brudi P, Triscari J. Consistency of effect of ezetimibe/simvastatin compared with intensified lipid-lowering treatment strategies in obese and non-obese diabetic subjects. Lipids Health Dis. 2013 Jul 16;12:103. doi: 10.1186/1476-511X-12-103.
- Rosen JB, Jimenez JG, Pirags V, Vides H, Hanson ME, Massaad R, McPeters G, Brudi P, Triscari J. A comparison of efficacy and safety of an ezetimibe/simvastatin combination compared with other intensified lipid-lowering treatment strategies in diabetic patients with symptomatic cardiovascular disease. Diab Vasc Dis Res. 2013 May;10(3):277-86. doi: 10.1177/1479164112465212. Epub 2013 Jan 3.
- Jimenez JG, Rosen JB, Pirags V, Massaad R, Hanson ME, Brudi P, Triscari J. The efficacy and safety of ezetimibe/simvastatin combination compared with intensified lipid-lowering treatment strategies in diabetic subjects with and without metabolic syndrome. Diabetes Obes Metab. 2013 Jun;15(6):513-22. doi: 10.1111/dom.12059. Epub 2013 Jan 25.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
April 1, 2009
Primary Completion (Actual)
March 1, 2011
Study Completion (Actual)
March 1, 2011
Study Registration Dates
First Submitted
March 12, 2009
First Submitted That Met QC Criteria
March 13, 2009
First Posted (Estimate)
March 16, 2009
Study Record Updates
Last Update Posted (Actual)
February 14, 2022
Last Update Submitted That Met QC Criteria
February 7, 2022
Last Verified
February 1, 2022
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Endocrine System Diseases
- Cardiovascular Diseases
- Diabetes Mellitus
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Atorvastatin
- Rosuvastatin Calcium
- Simvastatin
- Ezetimibe
Other Study ID Numbers
- 0653A-133
- 2009_559 (Other Identifier: Merck Study Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Yes
IPD Plan Description
http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf
http://engagezone.msd.com/ds_documentation.php
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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