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

August 13, 2024 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

Conditions

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

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
Drug: ezetimibe (plus simvastatin)
oral tablets; ezetimibe 10 mg (plus simvastatin 80 mg) once daily for 24 months
Other Names:
  • SCH 58235
  • ZETIA
  • SCH 465981
  • VYTORIN
Placebo Comparator: Placebo/Simva
Drug: placebo (plus simvastatin)
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

Organon and Co

Collaborators

Merck Sharp & Dohme LLC

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

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 (Estimated)

November 1, 2007

Study Record Updates

Last Update Posted (Actual)

August 15, 2024

Last Update Submitted That Met QC Criteria

August 13, 2024

Last Verified

February 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P02578

Plan for Individual participant data (IPD)

Study Data/Documents

  1. CSR Synopsis

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.

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