- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00552097
Effect of Ezetimibe Plus Simvastatin Versus Simvastatin Alone on Atherosclerosis in the Carotid Artery (ENHANCE)(P02578) (ENHANCE)
February 7, 2022 updated by: Organon and Co
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 Overview
Status
Completed
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
720
Phase
- Phase 3
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
30 years to 75 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: EZ/Simva
|
oral tablets; ezetimibe 10 mg (plus simvastatin 80 mg) once daily for 24 months
Other Names:
|
Placebo Comparator: Placebo/Simva
|
tablets; placebo to match ezetimibe 10 mg (plus simvastatin 80 mg) once daily for 24 months
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change in ultrasound-determined average carotid artery intima-media thickness (IMT) on a per subject basis between baseline and endpoint.
Time Frame: 24 months
|
24 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Proportion of subjects with a reduction in ultrasound-determined average carotid artery IMT between baseline and endpoint.
Time Frame: 24 months
|
24 months
|
Change in ultrasound-determined maximum carotid artery IMT on a per subject basis between baseline and endpoint.
Time Frame: 24 months
|
24 months
|
Proportion of subjects developing new carotid artery plaques between baseline and endpoint.
Time Frame: 24 months
|
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
|
24 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 1, 2002
Primary Completion (Actual)
April 25, 2006
Study Completion (Actual)
April 25, 2006
Study Registration Dates
First Submitted
October 31, 2007
First Submitted That Met QC Criteria
October 31, 2007
First Posted (Estimate)
November 1, 2007
Study Record Updates
Last Update Posted (Actual)
February 17, 2022
Last Update Submitted That Met QC Criteria
February 7, 2022
Last Verified
February 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Metabolic Diseases
- Arteriosclerosis
- Arterial Occlusive Diseases
- Lipid Metabolism Disorders
- Dyslipidemias
- Hypercholesterolemia
- Atherosclerosis
- Hyperlipidemias
- Hyperlipoproteinemias
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Simvastatin
- Ezetimibe
Other Study ID Numbers
- P02578
Plan for Individual participant data (IPD)
Study Data/Documents
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Atherosclerosis
-
University Hospital, CaenUnknownPeripheral Arterial Disease | Atherosclerosis Obliterans | Atherosclerosis Right Leg | Atherosclerosis Left LegFrance
-
Nantes University HospitalAbbottCompletedAtherosclerosis ObliteransFrance
-
Central Hospital, Nancy, FranceSuspended
-
Federal University of São PauloCompletedAtherosclerosis of ArteryBrazil
-
MedtronicActive, not recruitingAtherosclerosis of Femoral Artery | Obstructive Disease | Atherosclerosis of Popliteal ArteryFrance
-
Cabinet de Medecine Interne Générale Demetrio PitarchCompletedAtherosclerosis of Artery
-
Emory UniversityThe Robert W. Woodruff FoundationCompleted
-
Korea UniversityMinistry of Health & Welfare, KoreaCompletedAtherosclerosis | Noninvasive Imaging of AtherosclerosisKorea, Republic of
-
Zhejiang Zylox Medical Device Co., Ltd.RecruitingAtherosclerosis of Femoral ArteryGermany
-
VA Office of Research and DevelopmentCompletedSaphenous Vein Graft AtherosclerosisUnited States
Clinical Trials on ezetimibe (plus simvastatin)
-
University of Sao PauloCompletedCoronary Heart Disease
-
University of CologneMerck Sharp & Dohme LLCCompleted
-
University of OxfordNational Health and Medical Research Council, Australia; Merck Sharp & Dohme... and other collaboratorsCompleted
-
Merck Sharp & Dohme LLCCompleted
-
Peking Union Medical College HospitalUnknownAtherosclerosisChina
-
dr.Frank L.J. VisserenMerck Sharp & Dohme LLCCompletedThe PostprAndial eNdothelial Function After Combination of Ezetimibe and simvAstatin Study (PANACEA)Metabolic SyndromeNetherlands, Spain
-
Organon and CoCompleted
-
Organon and CoCompletedMyocardial Infarction | Hypercholesterolemia
-
Korea UniversityWithdrawn
-
Hue University of Medicine and PharmacyUniversità degli Studi di SassariUnknownChronic Kidney Diseases | HypercholesterolemiaVietnam