HypercholesterolemiaPhase 3NCT00651391
Effect of Ezetimibe Plus Simvastatin on Flow-Mediated Brachial Artery Vasoactivity in Subjects With Primary Hypercholesterolemia (Study P03336)
A Phase 3 study testing Ezetimibe + Simvastatin and Simvastatin in people with Hypercholesterolemia and Atherosclerosis, run by Organon and Co.
Trial summary
The purpose of this study is to evaluate the effect of ezetimibe coadministered with simvastatin compared with simvastatin alone when administered for 12 weeks on endothelial function as assessed by brachial artery reactivity testing (BART) using high-frequency ultrasound to image the brachial artery vasomotor… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypercholesterolemia, Atherosclerosis
- What is being tested?
- Ezetimibe + Simvastatin and Simvastatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2003to 1 Sep 2004
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults (18 years old and older) with primary hypercholesterolemia with a plasma LDL-C >=145 mg/dL and <=250 mg/dL, and plasma TG <=350 mg/dL after adequate drug washout.
- Postmenopausal women who are receiving postmenopausal hormonal therapy or raloxifene must be maintained on a stable hormone replacement therapy (HRT) or raloxifene regimen for at least 6 weeks prior to study entry and throughout the study period.
- All subjects must agree to refrain from drinking alcohol or caffeine containing beverages for 12 hours prior to each study visit at which a BART assessment is performed; be minimally active (eg, avoid excessive physical activity) for 12 hours prior to each study visit at which a BART assessment is performed; and be willing to observe the NCEP Step I diet, participate in the study, and complete all study-related procedures.
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
- Smoking, excessive alcohol consumption, underlying disease likely to limit life span to less than one year, or known hypersensitivity or any contraindication to simvastatin, ezetimibe, or nitroglycerin
- Existing hypercholesterolemia for which withholding approved lipid-lowering therapy for the duration of the study would be inappropriate
- The following concomitant illnesses: congestive heart failure NYHA Class III or IV; obstructive cardiomyopathy; uncontrolled cardiac arrhythmias; severe aortic stenosis; upper severe aortic stenosis; MI, CABG, or angioplasty within 6 months of study entry; uncontrolled hypertension; unstable or severe peripheral artery disease within 3 months of study entry; unstable angina pectoris; disorders of the hematologic, digestive or central nervous systems including cerebrovascular disease and degenerative disease that would limit study evaluation or participation; uncontrolled or newly diagnosed (within one month of study entry) diabetes mellitus; uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins (clinically euthyroid subjects on stable replacement doses of thyroid hormone are eligible for enrollment); known impairment of renal function (plasma creatinine >2.0 mg/dL), dysproteinemia, nephrotic syndrome or other renal disease (24-hour urinary protein 3+ or 1 gram); hepatobiliary or hepatic disease (subjects with AST or ALT >2 times the upper limit of reference range will be excluded); HIV positive; and known coagulopathy.
- Use of certain drugs, foods, or other agents known to alter lipid levels or to cause interactions with either ezetimibe or simvastatin
About this study
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Effect of Ezetimibe Plus Simvastatin Compared With Simvastatin Alone on Flow-Mediated Brachial Artery Vasoactivity in Subjects With Primary Hypercholesterolemia (The EFFECTS Trial)
The purpose of this study is to evaluate the effect of ezetimibe coadministered with simvastatin compared with simvastatin alone when administered for 12 weeks on endothelial function as assessed by brachial artery reactivity testing (BART) using high-frequency ultrasound to image the brachial artery vasomotor response to a flow-mediated stimulus (high-shear stress) in subjects with high cholesterol. The secondary objectives include evaluation of nitroglycerin-induced vasodilation. In addition, lipid parameters (low-density-lipoprotein cholesterol [LDL-C], high-density-lipoprotein cholesterol [HDL-C], triglycerides [TG], total cholesterol [TC]) and C reactive protein (CRP) will be assessed by treatment group.
- Conditions
- Hypercholesterolemia, Atherosclerosis
- Being tested
- Ezetimibe + Simvastatin, Simvastatin, Placebo
- Medical subject headings
- Hypercholesterolemia, Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ezetimibe + SimvastatinDrug
Also called SCH 58235
oral tablet of ezetimibe 10 mg plus simvastatin 20 mg once daily in the evening for 12 weeks
SimvastatinDrug
oral simvastatin 20 mg once daily in the evening for 12 weeks
PlaceboDrug
oral placebo once daily in the evening for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Ezetimibe + Simvastatin | Experimental | Not described Receives: Drug: Ezetimibe + Simvastatin |
| Simvastatin | Active comparator | Not described Receives: Drug: Simvastatin |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline to endpoint in flow-mediated vasodilation: percent change in the mean diameter between 1-minute, post-cuff release diameter and image obtained prior to cuff application.
Measured: Week 12
Secondary outcomes (2)
Change from baseline to endpoint in NTG-induced vasodilation: percent change in the diameter between the post-NTG and pre-NTG diameters.
Measured: Week 12
Changes from baseline to endpoint in LDL-C, HDL-C, TG, TC, and CRP.
Measured: Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2008 (estimated)
- Study start1 Oct 2003
- Primary completion1 Sep 2004
- Study completion1 Sep 2004
Why it stopped: Slow enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypercholesterolemiaStudies 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 28 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
- NCT00651391
- Sponsor's protocol ID
- P03336
- Status last verified
- Feb 2022
- First submitted
- 31 Mar 2008
- Last updated
- 15 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
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
- A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Effect of Ezetimibe Plus Simvastatin Compared With Simvastatin Alone on Flow-Mediated Brachial Artery Vasoactivity in Subjects With Primary Hypercholesterolemia (The EFFECTS Trial)
- ClinicalTrials.gov ID
- NCT00651391
- Acronym / sponsor ID
- P03336
- Conditions
- Hypercholesterolemia, Atherosclerosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow enrollment
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Organon and CoIndustry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 1 Oct 2003 (actual)
- Primary completion
- 1 Sep 2004 (actual)
- Study completion
- 1 Sep 2004 (actual)
- First posted
- 2 Apr 2008 (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 this study is to evaluate the effect of ezetimibe coadministered with simvastatin compared with simvastatin alone when administered for 12 weeks on endothelial function as assessed by brachial artery reactivity testing (BART) using high-frequency ultrasound to image the brachial artery vasomotor response to a flow-mediated stimulus (high-shear stress) in subjects with high cholesterol. The secondary objectives include evaluation of nitroglycerin-induced vasodilation. In addition, lipid parameters (low-density-lipoprotein cholesterol [LDL-C], high-density-lipoprotein cholesterol [HDL-C], triglycerides [TG], total cholesterol [TC]) and C reactive protein (CRP) will be assessed by treatment group.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Ezetimibe + Simvastatin | Experimental | Drug: Ezetimibe + Simvastatin |
| Simvastatin | Active comparator | Drug: Simvastatin |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adults (18 years old and older) with primary hypercholesterolemia with a plasma LDL-C >=145 mg/dL and <=250 mg/dL, and plasma TG <=350 mg/dL after adequate drug washout.
- Postmenopausal women who are receiving postmenopausal hormonal therapy or raloxifene must be maintained on a stable hormone replacement therapy (HRT) or raloxifene regimen for at least 6 weeks prior to study entry and throughout the study period.
- All subjects must agree to refrain from drinking alcohol or caffeine containing beverages for 12 hours prior to each study visit at which a BART assessment is performed; be minimally active (eg, avoid excessive physical activity) for 12 hours prior to each study visit at which a BART assessment is performed; and be willing to observe the NCEP Step I diet, participate in the study, and complete all study-related procedures.
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
- Smoking, excessive alcohol consumption, underlying disease likely to limit life span to less than one year, or known hypersensitivity or any contraindication to simvastatin, ezetimibe, or nitroglycerin
- Existing hypercholesterolemia for which withholding approved lipid-lowering therapy for the duration of the study would be inappropriate
- The following concomitant illnesses: congestive heart failure NYHA Class III or IV; obstructive cardiomyopathy; uncontrolled cardiac arrhythmias; severe aortic stenosis; upper severe aortic stenosis; MI, CABG, or angioplasty within 6 months of study entry; uncontrolled hypertension; unstable or severe peripheral artery disease within 3 months of study entry; unstable angina pectoris; disorders of the hematologic, digestive or central nervous systems including cerebrovascular disease and degenerative disease that would limit study evaluation or participation; uncontrolled or newly diagnosed (within one month of study entry) diabetes mellitus; uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins (clinically euthyroid subjects on stable replacement doses of thyroid hormone are eligible for enrollment); known impairment of renal function (plasma creatinine >2.0 mg/dL), dysproteinemia, nephrotic syndrome or other renal disease (24-hour urinary protein 3+ or 1 gram); hepatobiliary or hepatic disease (subjects with AST or ALT >2 times the upper limit of reference range will be excluded); HIV positive; and known coagulopathy.
- Use of certain drugs, foods, or other agents known to alter lipid levels or to cause 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 + SimvastatinAlso: SCH 58235oral tablet of ezetimibe 10 mg plus simvastatin 20 mg once daily in the evening for 12 weeks | Drug | Ezetimibe + Simvastatin |
| Simvastatinoral simvastatin 20 mg once daily in the evening for 12 weeks | Drug | Simvastatin |
| Placebooral placebo once daily in the evening for 12 weeks | Drug | Placebo |
Primary outcome
Change from baseline to endpoint in flow-mediated vasodilation: percent change in the mean diameter between 1-minute, post-cuff release diameter and image obtained prior to cuff application.
Time frame: Week 12
2 secondary outcomes
Change from baseline to endpoint in NTG-induced vasodilation: percent change in the diameter between the post-NTG and pre-NTG diameters.
Time frame: Week 12
Changes from baseline to endpoint in LDL-C, HDL-C, TG, TC, and CRP.
Time frame: Week 12
Results and safety
The study was stopped early (reason given: Slow enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2024.
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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 + Simvastatin and Simvastatin in people with Hypercholesterolemia and Atherosclerosis, 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 3 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: stopped early, 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 was stopped early (reason given: Slow enrollment). Results are not available in the source record.
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 from baseline to endpoint in flow-mediated vasodilation: percent change in the mean diameter between 1-minute, post-cuff release diameter and image obtained prior to cuff application. (time frame: Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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; AzTrials last refreshed its copy on 6 Nov 2026.