Clinical trial NCT00299884: Atorvastatin Versus Ezetimibe and Fenofibrate as a Lipid-lowering Strategy
Official title: The Comparison of the Efficacy of Ezetimibe and Fenofibrate Versus Atorvastatin Alone in the Lowering of LDL Cholesterol
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Dyslipidemia
Vascular Disease
Keywords: Randomized
non-blinded
prospective
open-label
LDL-C
HDL-C
Lead sponsor: Queen's University
Sponsor class: OTHER
First posted: 2006-03-07
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CROSSOVER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Subjects aged 18-85 with elevated LDL-C levels 3.0 mmol/L and greater.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: To examine the efficacy of a combination of ezetimibe and fenofibrate in comparison with that of atorvastatin in lowering LDL-C.
timeFrame: 12 weeks
Secondary outcomes:
measure: 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.
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Kingston
country: Canada
facility: Vascular Disease Prevention and Research Centre, Hotel Dieu Hospital
state: Ontario
Study officials:
affiliation: Vascular Disease Prevention and Research Centre
name: Stephen A LaHaye, MD
role: PRINCIPAL_INVESTIGATOR
References: