Ezetimibe and Atorvastatin vs. Atorvastatin in Patients Age 65 and Older at High Risk for Coronary Heart Disease (CHD)(0653-112)

A Multicenter, Randomized, Double-Blind, Parallel Arm, 12-Week Study to Evaluate the Efficacy and Safety of Ezetimibe 10 mg When Added to Atorvastatin 10 mg Versus Titration to Atorvastatin 20 mg and to 40 mg in Elderly Patients With Hypercholesterolemia at High Risk for CHD

A 12 week clinical trial in patients 65 years of age and older with hypercholesterolemia at high risk for coronary heart disease to study the effects of atorvastatin and ezetimibe given in combination and two higher doses of atorvastatin on lipid lowering.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Drug: ezetimibe and atorvastatin; Drug: Placebo (unspecified); Drug: atorvastatin

• Study Type: Interventional
• Enrollment (Actual): 1053
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient is age 65 or older
• Patient is willing to maintain cholesterol lowering diet
• Patient has hyperlipidemia with LDL level greater than 70 mg/dl or 100 mg/dl depending on their CHD risk category

Exclusion Criteria:

• A condition which, in the opinion of the investigator, would pose a risk to the patient or interfere with participation in the study
• Patient is unlikely to be compliant in taking study medication
• Patient with chronic or unstable medical condition
• Patient is taking unstable doses of medication
• Patient drinks more than 2 alcoholic drinks per day
• Patient has elevations in certain laboratory values (CK, AST, ALT)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 2	Drug: Placebo (unspecified); Placebo (unspecified) daily for 12 weeks; Drug: atorvastatin; Atorvastatin 20 mg daily for 6 weeks, and up-titrated to atorvastatin 40 mg daily for an additional 6 weeks
Active Comparator: 1	Drug: ezetimibe and atorvastatin; ezetimibe 10 mg and atorvastatin 10 mg daily for 12 weeks; Drug: Placebo (unspecified); Placebo (unspecified) daily for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent Change From Baseline in LDL-C at Week 6	Baseline and Week 6

Secondary Outcome Measures

Outcome Measure	Time Frame
Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12	Baseline and Week 12
Number of Patients Who Achieved Low Density Lipoprotein Cholesterol (LDL-C) <70 mg/dL at Week 6	Week 6
Number of Patients Who Achieved Low Density Lipoprotein Cholesterol (LDL-C) <70 mg/dL at Week 12	Week 12
Number of Patients Who Achieved LDL-C <100 mg/dL for Patients Without Atherosclerotic Vascular Disease (AVD) and LDL-C <70 mg/dL for Patients With Atherosclerotic Vascular Disease (AVD) at Week 6	Week 6
Number of Patients Who Achieved LDL-C<100 mg/dL for Patients Without AVD and LDL-C<70 mg/dL for Patients With AVD at Week 12	Week 12

Other Outcome Measures

Outcome Measure	Time Frame
Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 6	Baseline and Week 6
Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 12	Baseline and Week 12
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 6	Baseline and Week 6
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12	Baseine and Week 12
Percent Change From Baseline in Total Cholesterol (TC) at Week 6	Baseline and Week 6
Percent Change From Baseline in Total Cholesterol (TC) at Week 12	Baseline and Week 12
Percent Change From Baseline in Triglycerides (TG) at Week 6	Baseline and Week 6
Percent Change From Baseline in Triglycerides (TG) at Week 12	Baseline and Week 12
Percent Change From Baseline in Apo Lipoprotein B (Apo B) at Week 6	Baseline and Week 6
Percent Change From Baseline in Apo Lipoprotein B (Apo B) at Week 12	Baseline and Week 12
Percent Change From Baseline in Apo Lipoprotein A-I (Apo A-I) at Week 6	Baseline and Week 6
Percent Change From Baseline in Apo Lipoprotein A-I (Apo A-I) at Week 12	Baseline and Week 12
Percent Change From Baseline in Total Cholesterol (TC): High Density Lipoprotein Cholesterol (HDL-C) Ratio at Week 6	Baseline and Week 6
Percent Change From Baseline in Total Cholesterol (TC):High Density Lipoprotein Cholesterol (HDL-C) Ratio at Week 12	Baseline and Week 12
Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C):High Density Lipoprotein Cholesterol (HDL-C) Ratio at Week 6	Baseline and Week 6
Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C):High Density Lipoprotein Cholesterol (HDL-C) Ratio at Week 12	Baseline and Week 12
Percent Change From Baseline in Apo Lipoprotein B (Apo B):Apo Lipoprotein A-I (Apo A-I) Ratio at Week 6	Baseline and Week 6
Percent Change From Baseline in Apo Lipoprotein B (Apo B):Apo Lipoprotein A-I (Apo A-I) Ratio at Week 12	Baseline and Week 12
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL):High Density Lipoprotein Cholesterol (HDL-C) Ratio at Week 6	Baseline and Week 6
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL):High Density Lipoprotein Cholesterol (HDL-C) Ratio at Week 12	Baseline and Week 12
Percent Change From Baseline in Ratio of Highly Selective C-Reactive Protein (Hs-CRP) at Week 6	Baseline and Week 6
Percent Change From Baseline in Ratio of Highly Selective C-Reactive Protein (Hs-CRP) at Week 12	Baseline and Week 12

Collaborators and Investigators

• Sponsor: Organon and Co

Publications and helpful links

General Publications

• Zieve F, Wenger NK, Ben-Yehuda O, Constance C, Bird S, Lee R, Hanson ME, Jones-Burton C, Tershakovec AM. Safety and efficacy of ezetimibe added to atorvastatin versus up titration of atorvastatin to 40 mg in Patients > or = 65 years of age (from the ZETia in the ELDerly [ZETELD] study). Am J Cardiol. 2010 Mar 1;105(5):656-63. doi: 10.1016/j.amjcard.2009.10.029. Epub 2009 Dec 24.
• Constance C, Ben-Yehuda O, Wenger NK, Zieve F, Lin J, Hanson ME, Lowe RS, Tershakovec AM. Atorvastatin 10 mg plus ezetimibe versus titration to atorvastatin 40 mg: attainment of European and Canadian guideline lipid targets in high-risk subjects >/=65 years. Lipids Health Dis. 2014 Jan 13;13:13. doi: 10.1186/1476-511X-13-13.

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: January 3, 2007
• First Submitted That Met QC Criteria: January 4, 2007
• First Posted (Estimate): January 5, 2007

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

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Ezetimibe
• Other Study ID Numbers: 0653-112; MK0653-112; 2006_549

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