Effect of Ezetimibe Plus Simvastatin Versus Simvastatin Alone on Atherosclerosis in the Carotid Artery (ENHANCE)(P02578AM3)(COMPLETED)

Condition(s) targeted: Atherosclerosis; Hypercholesterolemia; Hyperlipoproteinemia Type II

Intervention: ezetimibe (plus simvastatin) (Drug); placebo (plus simvastatin) (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Schering-Plough

Official(s) and/or principal investigator(s):
Enrico P. Veltri, MD, Study Director, Affiliation: Schering-Plough

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

Study design: Prevention, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study

Primary outcome: Change in ultrasound-determined average carotid artery intima-media thickness (IMT) on a per subject basis between baseline and endpoint.

Secondary outcome:

Proportion of subjects with a reduction in ultrasound-determined average carotid artery IMT between baseline and endpoint.

Change in ultrasound-determined maximum carotid artery IMT on a per subject basis between baseline and endpoint.

Proportion of subjects developing new carotid artery plaques between baseline and endpoint.

Change in ultrasound-determined average carotid artery plus average common femoral artery IMT on a per subject basis between baseline and endpoint.

Minimum age: 30 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

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

Related publications:

Kastelein JJ, Sager PT, de Groot E, Veltri E. Comparison of ezetimibe plus simvastatin versus simvastatin monotherapy on atherosclerosis progression in familial hypercholesterolemia. Design and rationale of the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) trial. Am Heart J. 2005 Feb;149(2):234-9.

Starting date: June 2002
Ending date: April 2006
Last updated: June 19, 2008