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:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00092677
First received: September 23, 2004
Last updated: March 27, 2014
Last verified: March 2014
  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:


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) ] [ 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


Other Outcome Measures:
  • Cardiovascular Death [ Time Frame: Entire follow-up (median = 4.35 years) ] [ Designated as safety issue: No ]
    Number of participants that experienced cardiovascular death

  • Aortic Valve Replacement (AVR) [ Time Frame: Entire follow-up (median = 4.35 years) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    Number of participants that experienced nonfatal myocardial infarction (MI)

  • Coronary Artery Bypass Grafting (CABG) [ Time Frame: Entire follow-up (median = 4.35 years) ] [ Designated as safety issue: No ]
    Number of participants that experienced coronary artery bypass grafting (CABG)

  • Percutaneous Coronary Intervention (PCI) [ Time Frame: Entire follow-up (median = 4.35 years) ] [ Designated as safety issue: No ]
    Number of participants that experienced percutaneous coronary intervention (PCI)

  • Hospitalization for Unstable Angina [ Time Frame: Entire follow-up (median = 4.35 years) ] [ Designated as safety issue: No ]
    Number of participants that experienced hospitalization for unstable angina

  • Nonhemorrhagic Stroke [ Time Frame: Entire follow-up (median = 4.35 years) ] [ Designated as safety issue: No ]
    Number of participants that experienced nonhemorrhagic stroke

  • Death (Any Cause) [ Time Frame: Entire follow-up (median = 4.35 years) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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

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
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, see Learn About Clinical Studies.

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

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

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

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00092677     History of Changes
Other Study ID Numbers: 0653A-043, 2004_050
Study First Received: September 23, 2004
Results First Received: March 31, 2009
Last Updated: March 27, 2014
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
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 19, 2014