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

Sponsor

Organon and Co (Industry)

Overall Status

Completed

CT.gov ID

NCT00552097

Collaborator

Merck Sharp & Dohme LLC (Industry)

720

Enrollment

Arms

46.8

Actual Duration (Months)

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Atherosclerosis Hypercholesterolemia Hyperlipoproteinemia Type II	Drug: ezetimibe (plus simvastatin) Drug: placebo (plus simvastatin)	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

720 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

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)

Actual Study Start Date :

Jun 1, 2002

Actual Primary Completion Date :

Apr 25, 2006

Actual Study Completion Date :

Apr 25, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: EZ/Simva	Drug: ezetimibe (plus simvastatin) oral tablets; ezetimibe 10 mg (plus simvastatin 80 mg) once daily for 24 months Other Names: ZETIA VYTORIN SCH 58235 SCH 465981
Placebo Comparator: Placebo/Simva	Drug: placebo (plus simvastatin) tablets; placebo to match ezetimibe 10 mg (plus simvastatin 80 mg) once daily for 24 months

Arm

Intervention/Treatment

Experimental: EZ/Simva

Drug: ezetimibe (plus simvastatin)

oral tablets; ezetimibe 10 mg (plus simvastatin 80 mg) once daily for 24 months

Other Names:

ZETIA

VYTORIN

SCH 58235

SCH 465981

Placebo Comparator: Placebo/Simva

Drug: placebo (plus simvastatin)

tablets; placebo to match ezetimibe 10 mg (plus simvastatin 80 mg) once daily for 24 months

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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