Effect of Ezetimibe Plus Simvastatin Versus Simvastatin Alone on Atherosclerosis in the Carotid Artery (ENHANCE)(P02578)

Study Overview
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Brief Summary
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The purpose of the study is to determine whether ezetimibe plus simvastatin will be more effective than simvastatin alone in preventing progression of atherosclerosis of the inner layer of the carotid artery.

Official Title
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Effect of Combination Ezetimibe and High-Dose Simvastatin vs Simvastatin Alone on the Atherosclerotic Process in Subjects With Heterozygous Familial Hypercholesterolemia (The ENHANCE Trial)

Conditions
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Atherosclerosis, Hypercholesterolemia, Hyperlipoproteinemia Type II

Intervention / Treatment
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* Drug: ezetimibe (plus simvastatin)
* Drug: placebo (plus simvastatin)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Genotype-confirmed heterozygous familial hypercholesterolemia with written documentation of the genetic diagnosis at the time of screening and LDL-C >=210 mg/dL (5.43 mmol/L), or clinical diagnosis of heterozygous familial hypercholesterolemia, defined as LDL-C >=210 mg/dL (5.43 mmol/L) and at least one of the following: tendinous xanthoma child <18 years of age with hypercholesterolemia (LDL-C >159 mg/dL (4.11 mmol/L) has a sibling with hypercholesterolemia (LDL-C >190 mg/dL [4.91 mmol/L]) and tendinous xanthoma family history with an LDL-C value distribution pattern compatible with dominant autosomal transmission and at least one relative presenting fasting total cholesterol values >348 mg/dL (9.0 mmol/L) after exclusion of secondary causes of dyslipidemia LDL-C >=210 mg/dL (5.43 mmol/L) 1 week before randomization plasma triglyceride level <=400 mg/dL (4.52 mmol/L) Exclusion Criteria: pregnancy or any other situation, condition, or illness that, in the opinion of the investigator, may interfere with optimal participation in the study presence of an apolipoprotein B gene mutation with confirmed absence of an LDL receptor mutation in either allele undergoing LDL-apheresis or plasma apheresis unsuitable plaque or artery morphology use of certain drugs, foods, or other agents known to alter cholesterol levels or to cause pharmacokinetic interactions with either ezetimibe or simvastatin

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EZ/Simva<br> | Drug: ezetimibe (plus simvastatin)<br>* oral tablets; ezetimibe 10 mg (plus simvastatin 80 mg) once daily for 24 months<br>* Other names: SCH 465981;|
| Placebo Comparator: Placebo/Simva<br> | Drug: placebo (plus simvastatin)<br>* tablets; placebo to match ezetimibe 10 mg (plus simvastatin 80 mg) once daily for 24 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in ultrasound-determined average carotid artery intima-media thickness (IMT) on a per subject basis between baseline and endpoint. |  | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with a reduction in ultrasound-determined average carotid artery IMT between baseline and endpoint. |  | 24 months | 
| Change in ultrasound-determined maximum carotid artery IMT on a per subject basis between baseline and endpoint. |  | 24 months | 
| Proportion of subjects developing new carotid artery plaques between baseline and endpoint. |  | 24 months | 
| Change in ultrasound-determined average carotid artery plus average common femoral artery IMT on a per subject basis between baseline and endpoint. |  | 24 months |