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Aortic StenosisPhase 3NCT00092677

An Investigational Drug on Clinical Outcomes in Patients With Aortic Stenosis (Narrowing of the Major Blood Vessel of the Heart)(MK-0653A-043 AM4)(COMPLETED)

A Phase 3 study testing ezetimibe (+) simvastatin in people with Aortic Stenosis, run by Organon and Co.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to evaluate whether treatment with an investigational drug as compared to placebo will reduce the risk of major cardiovascular events in patients with aortic stenosis. Read more about this study

Who is it for?
Ages 45 to 85 years
Conditions the study is for
Aortic Stenosis
What is being tested?
ezetimibe (+) simvastatin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,873 participants
Where
No sites listed yet
Study dates
Jan 2001to Apr 2008
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 45 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients aged 45 to 85 with mild abnormalities of the aortic valve as confirmed by an echocardiogram.

Who cannot join

  • Patients previously in a trial using the study drug, or currently taking any medications that are not allowed in this study.

About this study

Official title: A Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Effects of Ezetimibe + Simvastatin on Clinical Outcomes in Patients With Aortic Stenosis

The purpose of this study is to evaluate whether treatment with an investigational drug as compared to placebo will reduce the risk of major cardiovascular events in patients with aortic stenosis.

Conditions
Aortic Stenosis
Being tested
ezetimibe (+) simvastatin, Comparator: Placebo
Medical subject headings
Aortic Valve Stenosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ezetimibe (+) simvastatinDrug

    Also called MK0653A

    Duration of Treatment: 4 years

  • Comparator: PlaceboDrug

    matching Placebo

Study groups in NCT00092677
Study groupRoleWhat they receive
EZ/Simva 10/40 mgExperimentalEzetimibe 10 mg + Simvastatin 40 mg
Receives: Drug: ezetimibe (+) simvastatin
PlaceboPlacebo comparatorNot described
Receives: Drug: Comparator: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants That Experienced One or More Components of the Composite Clinical Endpoint of MCE (Major Cardiovascular Events)

    Composite endpoint of MCE consists of cardiovascular death, AVR (aortic valve replacement) surgery, CHF(congestive heart failure) as a result of progression of aortic stenosis, nonfatal MI (myocardial infarction), CABG (coronary artery bypass) surgery, PCI (percutaneous coronary intervention), hospitalized unstable angina, and nonhemorrhagic stroke

    Measured: Entire follow-up (median = 4.35 years)

Secondary outcomes (3)
  1. Number of Participants That Experienced One or More Components of the Composite Clinical Endpoint of AVE (Aortic Valve Events)

    Composite endpoint of AVE (aortic valve events) consists of AVR surgery, CHF (as a result of progression of AS), or cardiovascular death

    Measured: Entire follow-up (median = 4.35 years)

  2. Number of Participants That Experienced One or More Components of the Composite Clinical Endpoint of ICE (Ischemic Cardiovascular Events)

    Composite endpoint of ICE (ischemic cardiovascular events) consists of cardiovascular death, nonfatal MI, CABG, PCI, hospitalized unstable angina, and nonhemorrhagic stroke

    Measured: Entire follow-up (median = 4.35 years)

  3. Change From Baseline in Peak Transaortic Jet Velocity

    Mean change from baseline in peak transaortic jet velocity

    Measured: Baseline to End of follow-up (median = 4.35 years) or pre-aortic valve replacement

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Sep 2004 (estimated)
  2. Study startJan 2001
  3. Primary completionApr 2008
  4. Study completionApr 2008

Resources

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
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
1,873 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00092677
Sponsor's protocol ID
0653A-043
Other IDs
2004_050
Status last verified
Feb 2022
First submitted
23 Sep 2004
Last updated
16 May 2024
Individual data sharing
No

Publications

  • Rossebo AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, Gerdts E, Gohlke-Barwolf C, Holme I, Kesaniemi YA, Malbecq W, Nienaber CA, Ray S, Skjaerpe T, Wachtell K, Willenheimer R; SEAS Investigators. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med. 2008 Sep 25;359(13):1343-56. doi: 10.1056/NEJMoa0804602. Epub 2008 Sep 2.

    PubMed 18765433
  • Steine K, Rossebo AB, Stugaard M, Pedersen TR. Left ventricular systolic and diastolic function in asymptomatic patients with moderate aortic stenosis. Am J Cardiol. 2008 Oct 1;102(7):897-901. doi: 10.1016/j.amjcard.2008.07.001. Epub 2008 Aug 26.

    PubMed 18805118
  • Bahlmann E, Gerdts E, Einarsen E, Midtbo H, Pedersen ER, Rossebo A, Willems S, Cramariuc D. Impact of sex-specific thresholds for low flow in assessment of prognosis in concordantly and discordantly graded aortic valve stenosis. Eur Heart J Cardiovasc Imaging. 2025 Jan 31;26(2):280-286. doi: 10.1093/ehjci/jeae272.

    PubMed 39467305
  • Hadziselimovic E, Greve AM, Sajadieh A, Olsen MH, Kesaniemi YA, Nienaber CA, Ray SG, Rossebo AB, Wachtell K, Nielsen OW. Association of high-sensitivity troponin T with outcomes in asymptomatic non-severe aortic stenosis: a post-hoc substudy of the SEAS trial. EClinicalMedicine. 2023 Feb 28;58:101875. doi: 10.1016/j.eclinm.2023.101875. eCollection 2023 Apr.

    PubMed 36915288
  • Bahlmann E, Einarsen E, Cramariuc D, Pedersen ER, Rossebo AB, Midtbo H, Willems S, Gerdts E. Prognosis in asymptomatic patients with discordantly graded aortic valve stenosis based on pressure recovery adjusted valve area. Open Heart. 2022 Nov;9(2):e002159. doi: 10.1136/openhrt-2022-002159.

    PubMed 36428084
  • Hadziselimovic E, Greve AM, Sajadieh A, Olsen MH, Kesaniemi YA, Nienaber CA, Ray SG, Rossebo AB, Willenheimer R, Wachtell K, Nielsen OW. Association of Annual N-Terminal Pro-Brain Natriuretic Peptide Measurements With Clinical Events in Patients With Asymptomatic Nonsevere Aortic Stenosis: A Post Hoc Substudy of the SEAS Trial. JAMA Cardiol. 2022 Apr 1;7(4):435-444. doi: 10.1001/jamacardio.2021.5916.

    PubMed 35171199
  • Bahlmann E, Einarsen E, Cramariuc D, Midtbo H, Mancusi C, Rossebo A, Willems S, Gerdts E. Low myocardial energetic efficiency is associated with increased mortality in aortic stenosis. Open Heart. 2021 Aug;8(2):e001720. doi: 10.1136/openhrt-2021-001720.

    PubMed 34426527
  • Einarsen E, Cramariuc D, Bahlmann E, Midtbo H, Chambers JB, Gerdts E. Higher Acceleration/Ejection Time Ratio Predicts Impaired Outcome in Aortic Valve Stenosis. Circ Cardiovasc Imaging. 2021 Jan;14(1):e011467. doi: 10.1161/CIRCIMAGING.120.011467. Epub 2021 Jan 19.

    PubMed 33461302
  • Greve AM, Bang CN, Boman K, Egstrup K, Kesaniemi YA, Ray S, Pedersen TR, Wachtell K. Relation of Lipid-Lowering Therapy to Need for Aortic Valve Replacement in Patients With Asymptomatic Mild to Moderate Aortic Stenosis. Am J Cardiol. 2019 Dec 1;124(11):1736-1740. doi: 10.1016/j.amjcard.2019.08.037. Epub 2019 Sep 7.

    PubMed 31586530
  • Gerdts E, Saeed S, Midtbo H, Rossebo A, Chambers JB, Einarsen E, Bahlmann E, Devereux R. Higher left ventricular mass-wall stress-heart rate product and outcome in aortic valve stenosis. Heart. 2019 Nov;105(21):1629-1633. doi: 10.1136/heartjnl-2018-314462. Epub 2019 Jun 1.

    PubMed 31154431
  • Bahlmann E, Cramariuc D, Saeed S, Chambers JB, Nienaber CA, Kuck KH, Lonnebakken MT, Gerdts E. Low systemic arterial compliance is associated with increased cardiovascular morbidity and mortality in aortic valve stenosis. Heart. 2019 Oct;105(19):1507-1514. doi: 10.1136/heartjnl-2018-314386. Epub 2019 May 15.

    PubMed 31092548
  • Hodges GW, Bang CN, Forman JL, Olsen MH, Boman K, Ray S, Kesaniemi YA, Eugen-Olsen J, Greve AM, Jeppesen JL, Wachtell K. Effect of simvastatin and ezetimibe on suPAR levels and outcomes. Atherosclerosis. 2018 May;272:129-136. doi: 10.1016/j.atherosclerosis.2018.03.030. Epub 2018 Mar 16.

    PubMed 29602140
  • Hodges GW, Bang CN, Eugen-Olsen J, Olsen MH, Boman K, Ray S, Kesaniemi AY, Jeppesen JL, Wachtell K. SuPAR predicts postoperative complications and mortality in patients with asymptomatic aortic stenosis. Open Heart. 2018 Jan 13;5(1):e000743. doi: 10.1136/openhrt-2017-000743. eCollection 2018.

    PubMed 29387432
  • Greve AM, Bang CN, Boman K, Egstrup K, Forman JL, Kesaniemi YA, Ray S, Pedersen TR, Best P, Rajamannan NM, Wachtell K. Effect Modifications of Lipid-Lowering Therapy on Progression of Aortic Stenosis (from the Simvastatin and Ezetimibe in Aortic Stenosis [SEAS] Study). Am J Cardiol. 2018 Mar 15;121(6):739-745. doi: 10.1016/j.amjcard.2017.12.011. Epub 2017 Dec 25.

    PubMed 29361285
  • Bang CN, Greve AM, Rossebo AB, Ray S, Egstrup K, Boman K, Nienaber C, Okin PM, Devereux RB, Wachtell K. Antihypertensive Treatment With beta-Blockade in Patients With Asymptomatic Aortic Stenosis and Association With Cardiovascular Events. J Am Heart Assoc. 2017 Nov 27;6(12):e006709. doi: 10.1161/JAHA.117.006709.

    PubMed 29180457

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing ezetimibe (+) simvastatin in people with Aortic Stenosis, 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 1 inclusion and 1 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 16 May 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?

Yes. Results are posted in the registry (first posted 27 May 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants That Experienced One or More Components of the Composite Clinical Endpoint of MCE (Major Cardiovascular Events) (time frame: Entire follow-up (median = 4.35 years)). 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 NCT00092677, which also lists 35 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 16 May 2024.

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