Clinical trial NCT00552097: Effect of Ezetimibe Plus Simvastatin Versus Simvastatin Alone on Atherosclerosis in the Carotid Artery (ENHANCE)(P02578)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Atherosclerosis
Hypercholesterolemia
Hyperlipoproteinemia Type II
Lead sponsor: Organon and Co
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2007-11-01
Enrollment: 720
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility 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

Primary outcomes:
measure: Change in ultrasound-determined average carotid artery intima-media thickness (IMT) on a per subject basis between baseline and endpoint.
timeFrame: 24 months
Secondary outcomes:
measure: Proportion of subjects with a reduction in ultrasound-determined average carotid artery IMT between baseline and endpoint.
timeFrame: 24 months
measure: Change in ultrasound-determined maximum carotid artery IMT on a per subject basis between baseline and endpoint.
timeFrame: 24 months
measure: Proportion of subjects developing new carotid artery plaques between baseline and endpoint.
timeFrame: 24 months
measure: Change in ultrasound-determined average carotid artery plus average common femoral artery IMT on a per subject basis between baseline and endpoint.
timeFrame: 24 months
Other outcomes:
Locations:
Study officials:
References:
citation: 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. doi: 10.1016/j.ahj.2004.06.024.
citation: 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. doi: 10.1056/NEJMoa0800742. Epub 2008 Mar 30.