Atorvastatin Versus Ezetimibe and Fenofibrate as a Lipid-lowering Strategy

The Comparison of the Efficacy of Ezetimibe and Fenofibrate Versus Atorvastatin Alone in the Lowering of LDL Cholesterol

The primary aim of this study is to evaluate the efficacy and non-inferiority of a lipid-lowering medication regimen comprised of the medications ezetimibe and fenofibrate taken daily, versus atorvastatin daily in lowering levels of low-density lipoprotein (LDL-C) cholesterol. Additionally, other aims would include effects on other types of blood cholesterol and examining the safety of the ezetimibe and fenofibrate regimen, as compared to atorvastatin.

Study Overview

• Status: Completed
• Conditions: Dyslipidemia; Vascular Disease
• Intervention / Treatment: Drug: Lipitor 20 mg; Drug: Combination Ezetrol 10 mg and Lipidil Supra 160 mg

Detailed Description

It has been demonstrated in several previous primary and secondary studies that lowering low-density lipoprotein cholesterol (LDL-C) with the use of medications such as 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors improves mortality and morbidity related to cardiovascular events in patients with hypercholesterolemia. Such inhibitors, which are known as 'statins', act to block the synthesis of cholesterol in the liver. These medications are generally well tolerated by the vast majority of patients, but a small number experience side effects, most seriously those of myopathies, rhabdomyolysis and elevated liver enzymes - recognition of this fact, that statins are not universally without problems, highlights the need for viable alternatives.

Ezetimibe is a relatively new medication in Canada, approved for use in patients with cholesterol problems. It is an intestinal cholesterol binder that is known to be well-tolerated, with side effects similar to placebo. Alone, it has a modest effect in the lowering of LDL-C. Fenofibrate is a medication that also works through the liver and has long been used to adjust blood lipid levels in patients with mixed lipid problems. Alone it also has a modest effect in the lowering of LDL-C. Recent study, however, has shown that the effect of ezetimibe and fenofibrate together in the lowering of LDL-C is greater than that of either drug alone. This combination, if as effective in this regard as atorvastatin, would prove a valid alternative to the use of the atorvastatin in the lowering of LDL-C, and a benefit for patients who have had problems tolerating statin therapy but still require medication for elevated cholesterol.

• Study Type: Observational
• Enrollment (Actual): 45

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Kingston, Ontario, Canada, K7L 5G2
      • Vascular Disease Prevention and Research Centre, Hotel Dieu Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Subjects aged 18-85 with elevated LDL-C levels 3.0 mmol/L and greater.

Description

Inclusion Criteria:

-Study is confined to subjects with elevated LDL-C levels 3.0 mmol/L and greater.

Exclusion Criteria:

• Abnormal liver enzymes (ie, AST, ALT greater than three times the upper limit of normal);
• Creatine kinase levels more than two times the upper limit of normal;
• Uncontrolled ethanol use (this may affect compliance);
• Pregnant or breastfeeding women or women not using adequate contraceptive methods;
• Previous history of intolerance or adverse effects with statins;
• Previous history of intolerance or adverse effects with fibric acid derivatives;
• Previous history of intolerance or adverse effects with ezetimibe;
• Uncontrolled diabetes (HbA1c > 10%);
• Recent myocardial infarction (within 6 weeks);
• Concurrent enrollment in another study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Crossover
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1; Lipitor 20 mg	Drug: Lipitor 20 mg; A/A for 6 weeks
2; Lipidil Supra 160 mg and Ezetrol 10 mg	Drug: Combination Ezetrol 10 mg and Lipidil Supra 160 mg; a/a for 6 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To examine the efficacy of a combination of ezetimibe and fenofibrate in comparison with that of atorvastatin in lowering LDL-C.	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
To examine the efficacy of a combination of ezetimibe and fenofibrate in comparison with that of atorvastatin in lowering triglyceride levels, raising HDL-C levels and lowering of hsCRP levels.	12 weeks

Collaborators and Investigators

• Sponsor: Queen's University
• Investigators: Principal Investigator: Stephen A LaHaye, MD, Vascular Disease Prevention and Research Centre

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (Actual): July 1, 2006
• Study Completion (Actual): July 1, 2006

Study Registration Dates

• First Submitted: September 9, 2005
• First Submitted That Met QC Criteria: March 6, 2006
• First Posted (Estimate): March 7, 2006

Study Record Updates

• Last Update Posted (Estimate): March 29, 2016
• Last Update Submitted That Met QC Criteria: March 28, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Randomized; open-label; LDL-C; prospective; HDL-C; non-blinded
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Metabolic Diseases; Lipid Metabolism Disorders; Vascular Diseases; Dyslipidemias; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Fenofibrate; Ezetimibe
• Other Study ID Numbers: DMED-816-04