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)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cardiovascular Disorder
Diabetes Mellitus
Keywords: cardiovascular disorder
Lead sponsor: Organon and Co
Sponsor class: INDUSTRY
First posted: 2009-03-16
Enrollment: 808
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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).
timeFrame: Baseline and Week 6
Secondary outcomes:
measure: 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
timeFrame: Baseline and Week 6
measure: 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
timeFrame: Baseline and Week 6
measure: Percent Change From Baseline in LDL-C After Switching to Treatment With Ezetimibe/Simvastatin vs Switching Treatment to Rosuvastatin
timeFrame: Baseline and Week 6
measure: Number of Participants Who Reached the Target LDL-Cholesterol Level of < 70 mg/dL (1.81 mmol/L)
timeFrame: Week 6
measure: 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)
timeFrame: Week 6
measure: 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)
timeFrame: Week 6
measure: Percent Change From Baseline in Total Cholesterol (TC)
timeFrame: Baseline and Week 6
measure: Percent Change From Baseline in Triglycerides
timeFrame: Baseline and Week 6
measure: Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C)
timeFrame: Baseline and Week 6
measure: Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)
timeFrame: Baseline and Week 6
measure: Percent Change From Baseline in LDL-C/HDL-C Ratio
timeFrame: Baseline and Week 6
measure: Percent Change From Baseline in TC/HDL-C Ratio
timeFrame: Baseline and Week 6
measure: Percent Change From Baseline in Non-HDL-C/HDL-C Ratio
timeFrame: Baseline and Week 6
measure: Percent Change From Baseline in Apolipoprotein B (Apo B)
timeFrame: Baseline and Week 6
measure: Percent Change From Baseline Apolipoprotein A-I (Apo A-I)
timeFrame: Baseline and Week 6
measure: Percent Change From Baseline in Apo B/Apo A-I Ratio
timeFrame: Baseline and Week 6
measure: Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP)
timeFrame: Baseline and Week 6
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.