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

• ClinicalTrials.gov Identifier: NCT00552097
• Recruitment Status: Completed
• First Posted: November 1, 2007
• Last Update Posted: February 17, 2022
• Sponsor: Organon and Co
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Organon and Co

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 (Clinical Trial)
• 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: June 1, 2002
• Actual Primary Completion Date: April 25, 2006
• Actual Study Completion Date: April 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

Outcome Measures

Primary Outcome Measures :

1. 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 Outcome Measures :

1. Proportion of subjects with a reduction in ultrasound-determined average carotid artery IMT between baseline and endpoint. [ Time Frame: 24 months ]
2. Change in ultrasound-determined maximum carotid artery IMT on a per subject basis between baseline and endpoint. [ Time Frame: 24 months ]
3. Proportion of subjects developing new carotid artery plaques between baseline and endpoint. [ Time Frame: 24 months ]
4. 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 ]

Eligibility Criteria

• Ages Eligible for Study: 30 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

No Contacts or Locations Provided

More Information

Study Data/Documents: CSR Synopsis 

Publications:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Erratum In: N Engl J Med. 2008 May 1;358(18):1977.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT00552097
• Other Study ID Numbers: P02578
• First Posted: November 1, 2007
• Last Update Posted: February 17, 2022
• Last Verified: February 2022

Additional relevant MeSH terms:

Atherosclerosis; Hypercholesterolemia; Hyperlipoproteinemias; Hyperlipidemias; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Simvastatin; Ezetimibe; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors