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

Primary Purpose

Atherosclerosis, Hypercholesterolemia, Hyperlipoproteinemia Type II

Status

Completed

Phase

Phase 3

Locations

Study Type

Interventional

Intervention

ezetimibe (plus simvastatin)

placebo (plus simvastatin)

About this trial

This is an interventional prevention trial for Atherosclerosis

Eligibility Criteria

30 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

EZ/Simva

Placebo/Simva

Arm Description

Outcomes

Primary Outcome Measures

Change in ultrasound-determined average carotid artery intima-media thickness (IMT) on a per subject basis between baseline and endpoint.

Secondary Outcome Measures

Proportion of subjects with a reduction in ultrasound-determined average carotid artery IMT between baseline and endpoint.

Change in ultrasound-determined maximum carotid artery IMT on a per subject basis between baseline and endpoint.

Proportion of subjects developing new carotid artery plaques between baseline and endpoint.

Change in ultrasound-determined average carotid artery plus average common femoral artery IMT on a per subject basis between baseline and endpoint.

Full Information

NCT ID

NCT00552097

First Posted

October 31, 2007

Last Updated

February 7, 2022

Sponsor

Organon and Co

Collaborators

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT00552097

Brief Title

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

Acronym

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)

Study Type

Interventional

2. Study Status

Record Verification Date

February 2022

Overall Recruitment Status

Completed

Study Start Date

June 1, 2002 (Actual)

Primary Completion Date

April 25, 2006 (Actual)

Study Completion Date

April 25, 2006 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Organon and Co

Collaborators

Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Atherosclerosis, Hypercholesterolemia, Hyperlipoproteinemia Type II

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

720 (Actual)

8. Arms, Groups, and Interventions

Arm Title

EZ/Simva

Arm Type

Experimental

Arm Title

Placebo/Simva

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

ezetimibe (plus simvastatin)

Other Intervention Name(s)

ZETIA, VYTORIN, SCH 58235, SCH 465981

Intervention Description

oral tablets; ezetimibe 10 mg (plus simvastatin 80 mg) once daily for 24 months

Intervention Type

Drug

Intervention Name(s)

placebo (plus simvastatin)

Intervention Description

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

Primary Outcome Measure Information:

Title

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 Measure Information:

Title

Proportion of subjects with a reduction in ultrasound-determined average carotid artery IMT between baseline and endpoint.

Time Frame

24 months

Title

Change in ultrasound-determined maximum carotid artery IMT on a per subject basis between baseline and endpoint.

Time Frame

24 months

Title

Proportion of subjects developing new carotid artery plaques between baseline and endpoint.

Time Frame

24 months

Title

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

30 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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

12. IPD Sharing Statement

Citations:

PubMed Identifier

15846260

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.

Results Reference

background

PubMed Identifier

18376000

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

Results Reference

derived

Available IPD and Supporting Information:

Available IPD/Information Type

CSR Synopsis

Available IPD/Information URL

http://www.merck.com/clinical-trials/policies-perspectives.html

Learn more about this trial

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

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