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

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:
  • Lipitor, Zocor
rosuvastatin 10 mg tablets, taken once daily for six weeks.
Other Names:
  • Crestor
Experimental: Ezetimibe/simvastatin
ezetimibe/simvastatin 10/20 mg tablets, taken once daily for six weeks.
Other Names:
  • Vytorin
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:
  • Lipitor, Zocor
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:
  • Lipitor, Zocor
simvastatin 40 mg or atorvastatin 20 mg tablets, taken once daily for six weeks.
Other Names:
  • Lipitor, Zocor

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.

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

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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