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

Phase 3

Completed

• Conditions: Hyperlipoproteinemia Type II; Atherosclerosis; Hypercholesterolemia
• Interventions: Drug: ezetimibe (plus simvastatin); Drug: placebo (plus simvastatin)

• Registration Number: NCT00552097
• Lead Sponsor: Organon and Co

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2002-06-01
• Primary Completion: 2006-04-25
• Study Completion: 2006-04-25
• Study First Submitted: 2007-10-31
• Study First Submitted QC: 2007-10-31
• Study First Posted: 2007-11-01
• Status Verified: 2022-02
• Last Update Submitted: 2024-08-13
• Last Update Posted: 2024-08-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 720

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
EZ/Simva	ezetimibe (plus simvastatin)	-
Placebo/Simva	placebo (plus simvastatin)	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
Proportion of subjects with a reduction in ultrasound-determined average carotid artery IMT 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