AtherosclerosisPhase 3ENHANCENCT00552097
Effect of Ezetimibe Plus Simvastatin Versus Simvastatin Alone on Atherosclerosis in the Carotid Artery (ENHANCE)(P02578)
A Phase 3 study testing ezetimibe (plus simvastatin) in people with Atherosclerosis and Hypercholesterolemia, run by Organon and Co.
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. Read more about this study
- Who is it for?
- Ages 30 to 75 years
- Conditions the study is for
- Atherosclerosis, Hypercholesterolemia, Hyperlipoproteinemia Type II
- What is being tested?
- ezetimibe (plus simvastatin)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 720 participants
- Where
- No sites listed yet
- Study dates
- 1 Jun 2002to 25 Apr 2006
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
About this study
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)
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.
- Being tested
- ezetimibe (plus simvastatin), placebo (plus simvastatin)
- Medical subject headings
- Atherosclerosis, Hypercholesterolemia, Hyperlipoproteinemia Type II
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ezetimibe (plus simvastatin)Drug
Also called ZETIA, VYTORIN, SCH 58235, SCH 465981
oral tablets; ezetimibe 10 mg (plus simvastatin 80 mg) once daily for 24 months
placebo (plus simvastatin)Drug
tablets; placebo to match ezetimibe 10 mg (plus simvastatin 80 mg) once daily for 24 months
| Study group | Role | What they receive |
|---|---|---|
| EZ/Simva | Experimental | Not described Receives: Drug: ezetimibe (plus simvastatin) |
| Placebo/Simva | Placebo comparator | Not described Receives: Drug: placebo (plus simvastatin) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in ultrasound-determined average carotid artery intima-media thickness (IMT) on a per subject basis between baseline and endpoint.
Measured: 24 months
Secondary outcomes (4)
Proportion of subjects with a reduction in ultrasound-determined average carotid artery IMT between baseline and endpoint.
Measured: 24 months
Change in ultrasound-determined maximum carotid artery IMT on a per subject basis between baseline and endpoint.
Measured: 24 months
Proportion of subjects developing new carotid artery plaques between baseline and endpoint.
Measured: 24 months
Change in ultrasound-determined average carotid artery plus average common femoral artery IMT on a per subject basis between baseline and endpoint.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2007 (estimated)
- Study start1 Jun 2002
- Primary completion25 Apr 2006
- Study completion25 Apr 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for AtherosclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 720 participants (actual)
Sponsor and investigators
- Lead sponsor
- Organon and Co
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00552097
- Sponsor's protocol ID
- P02578
- Acronym
- ENHANCE
- Status last verified
- Feb 2022
- First submitted
- 31 Oct 2007
- Last updated
- 15 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
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.
PubMed 15846260Kastelein 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.
PubMed 18376000
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT00552097
- Acronym / sponsor ID
- ENHANCE / P02578
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 720 participants (actual)
- Lead sponsor
- Organon and CoIndustry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 1 Jun 2002 (actual)
- Primary completion
- 25 Apr 2006 (actual)
- Study completion
- 25 Apr 2006 (actual)
- First posted
- 1 Nov 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| EZ/Simva | Experimental | Drug: ezetimibe (plus simvastatin) |
| Placebo/Simva | Placebo comparator | Drug: placebo (plus simvastatin) |
Who may qualify
- Ages
- 30 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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:
- LDL-C >=210 mg/dL (5.43 mmol/L) 1 week before randomization
- plasma triglyceride level <=400 mg/dL (4.52 mmol/L)
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ezetimibe (plus simvastatin)Also: ZETIA, VYTORIN, SCH 58235, SCH 465981oral tablets; ezetimibe 10 mg (plus simvastatin 80 mg) once daily for 24 months | Drug | EZ/Simva |
| placebo (plus simvastatin)tablets; placebo to match ezetimibe 10 mg (plus simvastatin 80 mg) once daily for 24 months | Drug | Placebo/Simva |
Primary outcome
Change in ultrasound-determined average carotid artery intima-media thickness (IMT) on a per subject basis between baseline and endpoint.
Time frame: 24 months
4 secondary outcomes
Proportion of subjects with a reduction in ultrasound-determined average carotid artery IMT between baseline and endpoint.
Time frame: 24 months
Change in ultrasound-determined maximum carotid artery IMT on a per subject basis between baseline and endpoint.
Time frame: 24 months
Proportion of subjects developing new carotid artery plaques between baseline and endpoint.
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2024.
- Background: PubMed 15846260Kastelein 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.
- Derived from this study: PubMed 18376000Kastelein 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ezetimibe (plus simvastatin) in people with Atherosclerosis and Hypercholesterolemia, run by Organon and Co.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in ultrasound-determined average carotid artery intima-media thickness (IMT) on a per subject basis between baseline and endpoint. (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00552097, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2024.