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)”

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.

Study Type: Interventional

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

Intervention(s) in this Clinical Trial

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

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: EZ/Simva
• Placebo Comparator: Placebo/Simva

Primary 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 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
    

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 30 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Schering-Plough

Overall Clinical Trial Officials and Contacts

Enrico P. Veltri, MD Study Director Schering-Plough  

Information obtained from ClinicalTrials.gov on August 27, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00552097

Study ID Number: P02578

ClinicalTrials.gov Identifier: NCT00552097

Health Authority: United States: Food and Drug Administration