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

Purpose

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.

Condition	Intervention	Phase
Atherosclerosis Hypercholesterolemia Hyperlipoproteinemia Type II	Drug: ezetimibe (plus simvastatin) Drug: placebo (plus simvastatin)	Phase III

Genetics Home Reference related topics:

hypercholesterolemia

MedlinePlus related topics:

Cholesterol Ultrasound

ChemIDplus related topics:

Simvastatin Ezetimibe Vytorin

U.S. FDA Resources

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

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)

Further study details as provided by Schering-Plough:

Primary Outcome Measures:

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

Secondary Outcome Measures:

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

Enrollment:	720
Study Start Date:	June 2002
Study Completion Date:	April 2006

Arms	Assigned Interventions
EZ/Simva: Experimental	Drug: ezetimibe (plus simvastatin) oral tablets; ezetimibe 10 mg (plus simvastatin 80 mg) once daily for 24 months
Placebo/Simva: Placebo Comparator	Drug: placebo (plus simvastatin) tablets; placebo to match ezetimibe 10 mg (plus simvastatin 80 mg) once daily for 24 months

Eligibility

Ages Eligible for Study:	30 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00552097

Sponsors and Collaborators

Schering-Plough

Merck

Investigators


Study Director:	Enrico P. Veltri, MD	Schering-Plough

More Information

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.

Publications indexed to this study:

Kastelein JJ, Akdim F, Stroes ES, Zwinderman AH, Bots ML, Stalenhoef AF, Visseren FL, Sijbrands EJ, Trip MD, Stein EA, Gaudet D, Duivenvoorden R, Veltri EP, Marais AD, de Groot E; ENHANCE Investigators. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med. 2008 Apr 3;358(14):1431-43. Epub 2008 Mar 30.

Study ID Numbers:	P02578
First Received:	October 31, 2007
Last Updated:	June 19, 2008
ClinicalTrials.gov Identifier:	NCT00552097
Health Authority:	United States: Food and Drug Administration

Study placed in the following topic categories:

Atherosclerosis

Arterial Occlusive Diseases

Lipid Metabolism, Inborn Errors

Hypercholesterolemia, autosomal dominant

Hyperlipidemias

Simvastatin

Hyperlipoproteinemia Type II

Vascular Diseases

Ezetimibe

Arteriosclerosis

Metabolism, Inborn Errors

Metabolic disorder

Hypercholesterolemia

Hyperlipoproteinemias

Dyslipidemias

Lipid Metabolism Disorders

Additional relevant MeSH terms:

Antimetabolites

Metabolic Diseases

Molecular Mechanisms of Pharmacological Action

Genetic Diseases, Inborn

Therapeutic Uses

Antilipemic Agents

Enzyme Inhibitors

Cardiovascular Diseases

Anticholesteremic Agents

Hydroxymethylglutaryl-CoA Reductase Inhibitors

Pharmacologic Actions

ClinicalTrials.gov processed this record on July 03, 2008

Sponsors and Collaborators:	Schering-Plough Merck
Information provided by:	Schering-Plough
ClinicalTrials.gov Identifier:	NCT00552097