Ezetimibe/Simvastatin (MK-0653A) Versus Rosuvastatin Versus Doubling Statin Dose in Participants With Cardiovascular Disease and Diabetes Mellitus (MK-0653A-133)(COMPLETED)

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Cardiovascular Disorder, Diabetes Mellitus

Intervention / Treatment
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* Drug: ezetimibe (+) simvastatin
* Drug: simvastatin 40 mg or atorvastatin 20 mg
* Drug: Rosuvastatin
* Drug: atorvastatin 10 mg or simvastatin 20 mg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ezetimibe/simvastatin<br> | Drug: ezetimibe (+) simvastatin<br>* ezetimibe/simvastatin 10/20 mg tablets, taken once daily for six weeks.<br>* Other names: Vytorin;Drug: atorvastatin 10 mg or simvastatin 20 mg<br>* 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.<br>* Other names: Lipitor, Zocor;|
| Active Comparator: Doubling statin dose<br> | Drug: simvastatin 40 mg or atorvastatin 20 mg<br>* simvastatin 40 mg or atorvastatin 20 mg tablets, taken once daily for six weeks.<br>* Other names: Lipitor, Zocor;Drug: atorvastatin 10 mg or simvastatin 20 mg<br>* 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.<br>* Other names: Lipitor, Zocor;|
| Active Comparator: Rosuvastatin<br> | Drug: Rosuvastatin<br>* rosuvastatin 10 mg tablets, taken once daily for six weeks.<br>* Other names: Crestor;Drug: atorvastatin 10 mg or simvastatin 20 mg<br>* 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.<br>* Other names: Lipitor, Zocor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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). |  | Baseline and Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |  | 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 |  | Baseline and Week 6 | 
| Percent Change From Baseline in LDL-C After Switching to Treatment With Ezetimibe/Simvastatin vs Switching Treatment to Rosuvastatin |  | Baseline and Week 6 | 
| Number of Participants Who Reached the Target LDL-Cholesterol Level of < 70 mg/dL (1.81 mmol/L) |  | 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) |  | 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) |  | Week 6 | 
| Percent Change From Baseline in Total Cholesterol (TC) |  | Baseline and Week 6 | 
| Percent Change From Baseline in Triglycerides |  | Baseline and Week 6 | 
| Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) |  | Baseline and Week 6 | 
| Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) |  | Baseline and Week 6 | 
| Percent Change From Baseline in LDL-C/HDL-C Ratio |  | Baseline and Week 6 | 
| Percent Change From Baseline in TC/HDL-C Ratio |  | Baseline and Week 6 | 
| Percent Change From Baseline in Non-HDL-C/HDL-C Ratio |  | Baseline and Week 6 | 
| Percent Change From Baseline in Apolipoprotein B (Apo B) |  | Baseline and Week 6 | 
| Percent Change From Baseline Apolipoprotein A-I (Apo A-I) |  | Baseline and Week 6 | 
| Percent Change From Baseline in Apo B/Apo A-I Ratio |  | Baseline and Week 6 | 
| Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) |  | Baseline and Week 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cardiovascular disorder