Official Title: “A Prospective Randomized Open Label Blinded Endpoint Multicenter Study in Patients With Coronary Artery Disease to Assess the LDL Lowering Effect of Switching to Ezetimibe (+) Simvastatin for Cholesterol Lowering, Compared the Dose of the Statin Used.”

In patients with coronary artery disease and a LDL-C level between 2.5 mmol/L and 5.0 mmol/L on a stable (> 4 weeks) statin starting dose (simvastatin 20 mg or atorvastatin 10 mg), investigate what the LCL-C lowering efficacy is of doubling the statin dose (to 40 mg simvastatin or 20 mg atorvastatin) versus a combination tablet of ezetimibe 10 mg plus simvastatin 20 mg once daily for 12 weeks. It is postulated that more patients reach their LDL-C treatment goal with the combination tablet compared to doubling the starting dose.

Furthermore, the effect of both treatment regimens on other lipid parameters, safety and LDL-subfractions will be measured.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: February 2007

Patients with simvastatin 20 mg or atorvastatin 10 mg were randomized to (1) double statin dose (to 40 mg simvastatin or 20 mg atorvastatin) or (2) switch to a combination tablet of ezetimibe 10 mg plus simvastatin 20 mg once daily for 12 weeks.

Intervention(s) in this Clinical Trial

• Drug: ezetimibe (+) simvastatin
  • Vytorin® combination tablet of ezetimibe 10 mg plus simvastatin 20 mg once daily for 12 weeks. Tablets
• Drug: simvastatin
  • Zocor®; simvastatin 40 mg once daily for 12 weeks. Tablets
• Drug: atorvastatin
  • 20 mg atorvastatin once daily for 12 weeks. Tablets

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Arm 1: Active comparator
• Experimental: 2
  • Arm 2: Drug

Primary Measures

• Switching to a combination tablet of ezetimibe 10 mg plus simvastatin 20 mg is superior to doubling the statin dose as demonstrated by the percentage of patients reaching goal after 12 weeks of treatment.
  • Time Frame: after 12 weeks of treatment
    Safety Issue?: No

Secondary Measures

• Switching to a combination tablet of ezetimibe 10 mg plus simvastatin 20 mg will lower LDL-C more than doubling the statin dose as demonstrated by the percentage change from treated baseline in total and LDL-cholesterol after 12 weeks of treatment.
  • Time Frame: after 12 weeks of treatment
    Safety Issue?: No

Inclusion Criteria:

• Patient is male or female 18 years of age.
• Patient is on a stable daily statin starting dose for the past 4 weeks of either: atorvastatin 10 mg or; simvastatin 20 mg
• lipid values while on statin monotherapy treatment: LDL-C level of > 2.5 mmol/L to * 5.0 mmol/L, triglycerides < 4.0 mmol/L and total cholesterol < 7.0 mmol/L.
• Patient with established coronary artery disease such as stable angina; history of myocardial infarction; history of percutaneous coronary intervention (PTCA with or without stent placement); coronary stenosis on angiography; history of unstable angina or non-Q wave myocardial infarction; history of coronary artery bypass graft surgery (CABG); positive MIBI scan. Patients have to be in a stable medical condition.

Exclusion Criteria:

• Patients in whom cholesterol lowering medication regime has changed in the previous 4 weeks.
• Patients who have been treated with any other investigational drug within 3 months of
Visit 1.
• Patients who are pregnant or lactating.
• Any condition or situation which, in the opinion of the investigator, might pose a risk to the patient or interfere with participation in the study.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Merck

Overall Clinical Trial Officials and Contacts

Medical Monitor Study Director Merck  

Information obtained from ClinicalTrials.gov on October 15, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00166530

Study ID Number: 2005_059

ClinicalTrials.gov Identifier: NCT00166530

Health Authority: Netherlands: Medicines Evaluation Board (MEB)