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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)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00092677
First Posted: September 28, 2004
Last Update Posted: April 6, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
  Purpose
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.

Condition Intervention Phase
Aortic Stenosis Drug: ezetimibe (+) simvastatin Drug: Comparator: Placebo Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • 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) ]
    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


Secondary Outcome Measures:
  • Number of Participants That Experienced One or More Components of the Composite Clinical Endpoint of AVE (Aortic Valve Events) [ Time Frame: Entire follow-up (median = 4.35 years) ]
    Composite endpoint of AVE (aortic valve events) consists of AVR surgery, CHF (as a result of progression of AS), or cardiovascular death

  • Number of Participants That Experienced One or More Components of the Composite Clinical Endpoint of ICE (Ischemic Cardiovascular Events) [ Time Frame: Entire follow-up (median = 4.35 years) ]
    Composite endpoint of ICE (ischemic cardiovascular events) consists of cardiovascular death, nonfatal MI, CABG, PCI, hospitalized unstable angina, and nonhemorrhagic stroke

  • Change From Baseline in Peak Transaortic Jet Velocity [ Time Frame: Baseline to End of follow-up (median = 4.35 years) or pre-aortic valve replacement ]
    Mean change from baseline in peak transaortic jet velocity


Other Outcome Measures:
  • Cardiovascular Death [ Time Frame: Entire follow-up (median = 4.35 years) ]
    Number of participants that experienced cardiovascular death

  • Aortic Valve Replacement (AVR) [ Time Frame: Entire follow-up (median = 4.35 years) ]
    Number of participants that experienced aortic valve replacement (AVR)

  • Congestive Heart Failure (CHF) Due to Progression of Aortic Stenosis (AS) [ Time Frame: Entire follow-up (median = 4.35 years) ]
    Number of participants that experienced Congestive Heart Failure (CHF) due to progression of aortic stenosis (AS)

  • Nonfatal Myocardial Infarction (MI) [ Time Frame: Entire follow-up (median = 4.35 years) ]
    Number of participants that experienced nonfatal myocardial infarction (MI)

  • Coronary Artery Bypass Grafting (CABG) [ Time Frame: Entire follow-up (median = 4.35 years) ]
    Number of participants that experienced coronary artery bypass grafting (CABG)

  • Percutaneous Coronary Intervention (PCI) [ Time Frame: Entire follow-up (median = 4.35 years) ]
    Number of participants that experienced percutaneous coronary intervention (PCI)

  • Hospitalization for Unstable Angina [ Time Frame: Entire follow-up (median = 4.35 years) ]
    Number of participants that experienced hospitalization for unstable angina

  • Nonhemorrhagic Stroke [ Time Frame: Entire follow-up (median = 4.35 years) ]
    Number of participants that experienced nonhemorrhagic stroke

  • Death (Any Cause) [ Time Frame: Entire follow-up (median = 4.35 years) ]
    Number of participants that died (any cause)

  • Percent Change in Time Weighted Average Total Cholesterol From Baseline to End of Follow-up [ Time Frame: Baseline to End of follow-up (median = 4.35 years) ]
    Mean percent change (time-weighted average over follow-up) from baseline: Time-weighted average calculated using values at week 8, week 24, year 1 and every 6 months with time interval (days) between 2 successive values used as the weighting factor. For the first follow-up value, the weight was the number of days from randomization.

  • Percent Change in Time Weighted Average Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to End of Follow-up [ Time Frame: Baseline to End of follow-up (median = 4.35 years) ]
    Mean percent change (time-weighted average over follow-up) from baseline: Time-weighted average calculated using values at week 8, week 24, year 1 and every 6 months with time interval (days) between 2 successive values used as the weighting factor. For the first follow-up value, the weight was the number of days from randomization.

  • Percent Change in Time Weighted Average High-density Lipoprotein Cholesterol (HDL-C) From Baseline to End of Follow-up [ Time Frame: Baseline to End of follow-up (median = 4.35 years) ]
    Mean percent change (time-weighted average over follow-up) from baseline: Time-weighted average calculated using values at week 8, week 24, year 1 and every 6 months with time interval (days) between 2 successive values used as the weighting factor. For the first follow-up value, the weight was the number of days from randomization.

  • Percent Change in Time Weighted Average Triglycerides From Baseline to End of Follow-up [ Time Frame: Baseline to End of follow-up (median = 4.35 years) ]
    Mean percent change (time-weighted average over follow-up) from baseline: Time-weighted average calculated using values at week 8, week 24, year 1 and every 6 months with time interval (days) between 2 successive values used as the weighting factor. For the first follow-up value, the weight was the number of days from randomization.


Enrollment: 1873
Study Start Date: January 2001
Study Completion Date: April 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EZ/Simva 10/40 mg
Ezetimibe 10 mg + Simvastatin 40 mg
Drug: ezetimibe (+) simvastatin
Duration of Treatment: 4 years
Other Name: MK0653A
Placebo Comparator: Placebo Drug: Comparator: Placebo
matching Placebo

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   45 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • Patients previously in a trial using the study drug, or currently taking any medications that are not allowed in this study.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00092677


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Nielsen OW, Sajadieh A, Sabbah M, Greve AM, Olsen MH, Boman K, Nienaber CA, Kesäniemi YA, Pedersen TR, Willenheimer R, Wachtell K. Assessing Optimal Blood Pressure in Patients With Asymptomatic Aortic Valve Stenosis: The Simvastatin Ezetimibe in Aortic Stenosis Study (SEAS). Circulation. 2016 Aug 9;134(6):455-68. doi: 10.1161/CIRCULATIONAHA.115.021213. Epub 2016 Aug 2.
Bang CN, Greve AM, La Cour M, Boman K, Gohlke-Bärwolf C, Ray S, Pedersen T, Rossebø A, Okin PM, Devereux RB, Wachtell K. Effect of Randomized Lipid Lowering With Simvastatin and Ezetimibe on Cataract Development (from the Simvastatin and Ezetimibe in Aortic Stenosis Study). Am J Cardiol. 2015 Dec 15;116(12):1840-4. doi: 10.1016/j.amjcard.2015.09.026. Epub 2015 Oct 3.
Gerdts E, Rossebø AB, Pedersen TR, Cioffi G, Lønnebakken MT, Cramariuc D, Rogge BP, Devereux RB. Relation of Left Ventricular Mass to Prognosis in Initially Asymptomatic Mild to Moderate Aortic Valve Stenosis. Circ Cardiovasc Imaging. 2015 Nov;8(11):e003644; discussion e003644. doi: 10.1161/CIRCIMAGING.115.003644.
Blyme A, Asferg C, Nielsen OW, Sehestedt T, Kesäniemi YA, Gohlke-Bärwolf C, Boman K, Willenheimer R, Ray S, Nienaber CA, Rossebø A, Wachtell K, Olsen MH. High sensitivity C reactive protein as a prognostic marker in patients with mild to moderate aortic valve stenosis during lipid-lowering treatment: an SEAS substudy. Open Heart. 2015 Feb 4;2(1):e000152. doi: 10.1136/openhrt-2014-000152. eCollection 2015.
Greve AM, Bang CN, Berg RM, Egstrup K, Rossebø AB, Boman K, Nienaber CA, Ray S, Gohlke-Baerwolf C, Nielsen OW, Okin PM, Devereux RB, Køber L, Wachtell K. Resting heart rate and risk of adverse cardiovascular outcomes in asymptomatic aortic stenosis: the SEAS study. Int J Cardiol. 2015 Feb 1;180:122-8. doi: 10.1016/j.ijcard.2014.11.181. Epub 2014 Nov 26.
Cramariuc D, Rogge BP, Lønnebakken MT, Boman K, Bahlmann E, Gohlke-Bärwolf C, Chambers JB, Pedersen TR, Gerdts E. Sex differences in cardiovascular outcome during progression of aortic valve stenosis. Heart. 2015 Feb;101(3):209-14. doi: 10.1136/heartjnl-2014-306078. Epub 2014 Oct 9.
Jander N, Hochholzer W, Kaufmann BA, Bahlmann E, Gerdts E, Boman K, Chambers JB, Nienaber CA, Ray S, Rossebo A, Pedersen TR, Wachtell K, Gohlke-Bärwolf C, Neumann FJ, Minners J. Velocity ratio predicts outcomes in patients with low gradient severe aortic stenosis and preserved EF. Heart. 2014 Dec;100(24):1946-53. doi: 10.1136/heartjnl-2014-305763. Epub 2014 Sep 12.
Greve AM, Dalsgaard M, Bang CN, Egstrup K, Rossebø AB, Boman K, Cramariuc D, Nienaber CA, Ray S, Gohlke-Baerwolf C, Okin PM, Devereux RB, Køber L, Wachtell K. Usefulness of the electrocardiogram in predicting cardiovascular mortality in asymptomatic adults with aortic stenosis (from the Simvastatin and Ezetimibe in Aortic Stenosis Study). Am J Cardiol. 2014 Sep 1;114(5):751-6. doi: 10.1016/j.amjcard.2014.06.006. Epub 2014 Jun 21.
Greve AM, Dalsgaard M, Bang CN, Egstrup K, Ray S, Boman K, Rossebø AB, Gohlke-Baerwolf C, Devereux RB, Køber L, Wachtell K. Stroke in patients with aortic stenosis: the Simvastatin and Ezetimibe in Aortic Stenosis study. Stroke. 2014 Jul;45(7):1939-46. doi: 10.1161/STROKEAHA.114.005296. Epub 2014 Jun 5.
Minners J, Gohlke-Baerwolf C, Kaufmann BA, Bahlmann E, Gerdts E, Boman K, Chambers JB, Nienaber CA, Willenheimer R, Wachtell K, Holme I, Pedersen TR, Neumann FJ, Jander N. Adjusting parameters of aortic valve stenosis severity by body size. Heart. 2014 Jul;100(13):1024-30. doi: 10.1136/heartjnl-2013-305225. Epub 2014 Apr 29.
Bahlmann E, Gerdts E, Cramariuc D, Gohlke-Baerwolf C, Nienaber CA, Wachtell K, Seifert R, Chambers JB, Kuck KH, Ray S. Prognostic value of energy loss index in asymptomatic aortic stenosis. Circulation. 2013 Mar 12;127(10):1149-56. doi: 10.1161/CIRCULATIONAHA.112.078857. Epub 2013 Jan 28.
Greve AM, Gerdts E, Boman K, Gohlke-Baerwolf C, Rossebø AB, Devereux RB, Køber L, Ray S, Willenheimer R, Wachtell K. Impact of QRS duration and morphology on the risk of sudden cardiac death in asymptomatic patients with aortic stenosis: the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) Study. J Am Coll Cardiol. 2012 Mar 27;59(13):1142-9. doi: 10.1016/j.jacc.2011.12.020.
Holme I, Pedersen TR, Boman K, Egstrup K, Gerdts E, Kesäniemi YA, Malbecq W, Ray S, Rossebø AB, Wachtell K, Willenheimer R, Gohlke-Bärwolf C. A risk score for predicting mortality in patients with asymptomatic mild to moderate aortic stenosis. Heart. 2012 Mar;98(5):377-83. doi: 10.1136/heartjnl-2011-300475. Epub 2011 Dec 8.
Greve AM, Boman K, Gohlke-Baerwolf C, Kesäniemi YA, Nienaber C, Ray S, Egstrup K, Rossebø AB, Devereux RB, Køber L, Willenheimer R, Wachtell K. Clinical implications of electrocardiographic left ventricular strain and hypertrophy in asymptomatic patients with aortic stenosis: the Simvastatin and Ezetimibe in Aortic Stenosis study. Circulation. 2012 Jan 17;125(2):346-53. doi: 10.1161/CIRCULATIONAHA.111.049759. Epub 2011 Dec 6.
Cramariuc D, Cioffi G, Rieck AE, Devereux RB, Staal EM, Ray S, Wachtell K, Gerdts E. Low-flow aortic stenosis in asymptomatic patients: valvular-arterial impedance and systolic function from the SEAS Substudy. JACC Cardiovasc Imaging. 2009 Apr;2(4):390-9. doi: 10.1016/j.jcmg.2008.12.021.
Peto R, Emberson J, Landray M, Baigent C, Collins R, Clare R, Califf R. Analyses of cancer data from three ezetimibe trials. N Engl J Med. 2008 Sep 25;359(13):1357-66. doi: 10.1056/NEJMsa0806603. Epub 2008 Sep 2.

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00092677     History of Changes
Other Study ID Numbers: 0653A-043
2004_050 ( Other Identifier: Merck Study Number )
First Submitted: September 23, 2004
First Posted: September 28, 2004
Results First Submitted: March 31, 2009
Results First Posted: May 27, 2009
Last Update Posted: April 6, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php


Additional relevant MeSH terms:
Constriction, Pathologic
Aortic Valve Stenosis
Pathological Conditions, Anatomical
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Ventricular Outflow Obstruction
Simvastatin
Ezetimibe
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors


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