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

Atherosclerosis Clinical Trial

— ENHANCE  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00552097
• Other study ID #: P02578
• Status: Completed
• Phase: Phase 3
• Start date: June 1, 2002
• Est. completion date: April 25, 2006

Study information

• Verified date: February 2022
• Source: Organon and Co
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 720
• Est. completion date: April 25, 2006
• Est. primary completion date: April 25, 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Atherosclerosis
• Hypercholesterolemia
• Hyperlipidemias
• Hyperlipoproteinemia Type II
• Hyperlipoproteinemias

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Organon and Co	Merck Sharp & Dohme Corp.

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in ultrasound-determined average carotid artery intima-media thickness (IMT) on a per subject basis between baseline and endpoint.		24 months
Secondary	Proportion of subjects with a reduction in ultrasound-determined average carotid artery IMT between baseline and endpoint.		24 months
Secondary	Change in ultrasound-determined maximum carotid artery IMT on a per subject basis between baseline and endpoint.		24 months
Secondary	Proportion of subjects developing new carotid artery plaques between baseline and endpoint.		24 months
Secondary	Change in ultrasound-determined average carotid artery plus average common femoral artery IMT on a per subject basis between baseline and endpoint.		24 months