An Investigational Drug on Clinical Outcomes in Patients With Aortic Stenosis (Narrowing of the Major Blood Vessel of the Heart) - Full Text View

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 Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, 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:

Genetics Home Reference related topics: supravalvular aortic stenosis

Drug Information available for: Simvastatin Ezetimibe

U.S. FDA Resources

Further study details as provided by Merck:

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) ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Mean change from baseline in peak transaortic jet velocity

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

Ages Eligible for Study:	45 Years to 85 Years
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00092677

Sponsors and Collaborators

Merck

Investigators

Study Director:

Medical Monitor

Merck

More Information

Publications:

Rossebø AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, Gerdts E, Gohlke-Bärwolf C, Holme I, Kesäniemi 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. Epub 2008 Sep 2.

Steine K, Rossebø 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. Epub 2008 Aug 26.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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. 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. 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.

Responsible Party:	Executive Vice President, Clinical and Quantitative Sciences, Merck Sharp & Dohme Corp
ClinicalTrials.gov Identifier:	NCT00092677 History of Changes
Other Study ID Numbers:	2004_050, MK0653A-043
Study First Received:	September 23, 2004
Results First Received:	March 31, 2009
Last Updated:	June 4, 2010
Health Authority:	Norway: Norwegian Medicines Agency

Additional relevant MeSH terms:

Aortic Valve Stenosis
Constriction, Pathologic
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Ventricular Outflow Obstruction
Pathological Conditions, Anatomical
Simvastatin
Ezetimibe

Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on May 22, 2013