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IMPROVE-IT: Examining Outcomes in Subjects With Acute Coronary Syndrome: Vytorin (Ezetimibe/Simvastatin) vs Simvastatin (P04103)

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ClinicalTrials.gov Identifier: NCT00202878
Recruitment Status : Completed
First Posted : September 20, 2005
Results First Posted : September 30, 2015
Last Update Posted : September 21, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE September 13, 2005
First Posted Date  ICMJE September 20, 2005
Results First Submitted Date  ICMJE August 28, 2015
Results First Posted Date  ICMJE September 30, 2015
Last Update Posted Date September 21, 2018
Actual Study Start Date  ICMJE October 17, 2005
Actual Primary Completion Date September 18, 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 28, 2015)
Time to First Occurrence of Cardiovascular Death, Major Coronary Event, or Non-fatal Stroke (Kaplan-Meier Estimate of Percentage of Participants Experiencing a Qualifying Event) [ Time Frame: Up to approximately 9 years ]
The time (in months) from study start to the first occurrence of any of the following clinical outcomes was recorded: cardiovascular death, major coronary Event (non-fatal myocardial infarction [MI], documented unstable angina [UA] requiring hospitalization, or coronary revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) ≥ 30 days after randomization), or non-fatal Stroke. A Clinical Endpoints Committee (CEC) reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or who were lost to follow-up and had no event were censored at the time of last available information (last study visit). The Kaplan-Meier estimate reports the percentage of participants who experienced cardiovascular death, major coronary event, or non-fatal stroke within 7 years from randomization.
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00202878 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 28, 2015)
  • Time to First Occurrence of Death From Any Cause, Major Coronary Event, or Non-fatal Stroke (Kaplan-Meier Estimate of Percentage of Participants Experiencing a Qualifying Event) [ Time Frame: Up to approximately 9 years ]
    The time (in months) from study start to the first occurrence of any of the following clinical outcomes was recorded: death from any cause, major coronary event (non-fatal myocardial infarction, documented unstable angina requiring hospitalization, or coronary revascularization with percutaneous coronary intervention or coronary artery bypass grafting ≥ 30 days after randomization), or non-fatal stroke. A Clinical Endpoints Committee (CEC) reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or who were lost to follow-up and had no event were censored at the time of last available information (last study visit). The Kaplan-Meier estimate reports the percentage of participants who experienced death from any cause, major coronary event, or non-fatal stroke within 7 years from randomization.
  • Time to First Occurrence of Coronary Heart Disease (CHD) Death, Non-fatal MI, or Urgent Coronary Revascularization With PCI or CABG ≥ 30 Days After Randomization (Kaplan-Meier Estimate of Percentage of Participants Experiencing a Qualifying Event) [ Time Frame: Up to approximately 9 years ]
    The time (in months) from study start to the first occurrence of any of the following clinical outcomes was recorded: CHD death, non-fatal MI, or urgent coronary revascularization with PCI or CABG ≥ 30 days after randomization. A Clinical Endpoints Committee (CEC) reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or who were lost to follow-up and had no event were censored at the time of last available information (last study visit). The Kaplan-Meier estimate reports the percentage of participants who experienced CHD death, non-fatal MI, or urgent coronary revascularization with PCI or CABG ≥ 30 days after randomization within 7 years from randomization.
  • Time to First Occurrence of CV Death, Nonfatal MI, UA With Hospitalization, All Revascularization Occurring ≥30 Days After Randomization, and Non-fatal Stroke (Kaplan-Meier Estimate of Percentage of Participants Experiencing a Qualifying Event) [ Time Frame: Up to approximately 9 years ]
    The time (in months) from study start to the first occurrence of any of the following clinical outcomes was recorded: CV death, non-fatal MI, documented UA that requires admission into a hospital, all revascularization (including non-coronary) occurring at least 30 days after randomization, and non-fatal stroke. A Clinical Endpoints Committee (CEC) reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or who were lost to follow-up and had no event were censored at the time of last available information (last study visit). The Kaplan-Meier estimate reports the percentage of participants who experienced CV death, non-fatal MI, unstable angina with hospitalization, all revascularization occurring ≥ 30 days after randomization, and non-fatal stroke within 7 Years from randomization.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE IMPROVE-IT: Examining Outcomes in Subjects With Acute Coronary Syndrome: Vytorin (Ezetimibe/Simvastatin) vs Simvastatin (P04103)
Official Title  ICMJE A Multicenter, Double-Blind, Randomized Study to Establish the Clinical Benefit and Safety of Vytorin (Ezetimibe/Simvastatin Tablet) vs Simvastatin Monotherapy in High-Risk Subjects Presenting With Acute Coronary Syndrome (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial - IMPROVE IT)
Brief Summary This is a randomized, active-control, double-blind study of subjects with stabilized high-risk acute coronary syndrome (ACS). The primary objective is to evaluate the clinical benefit of Ezetimibe/Simvastatin Combination 10/40 (single tablet, under the brand VYTORIN in the United States) compared with Simvastatin 40 mg. As per the original protocol, if low-density lipoprotein cholesterol (LDL-C) response was inadequate, the dose of simvastatin in the VYTORIN arm or simvastatin arm, could be increased to 80 mg (Note: per June 2011 protocol amendment, criteria for continued use of 80 mg simvastatin were modified and new increases of simvastatin dose to 80 mg were stopped). Clinical benefit will be defined as the reduction in the risk of the occurrence of the composite endpoint of cardiovascular (CV) death, major coronary events, and stroke.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Hypercholesterolemia
  • Myocardial Infarction
Intervention  ICMJE
  • Drug: ezetimibe/simvastatin
    Ezetimibe/simvastatin 10/40 mg per day from randomization through the end of participation. As per the original protocol, if LDL-C response was inadequate, the dose of simvastatin in the VYTORIN arm or simvastatin arm, could be increased to 80 mg (Note: per June 2011 protocol amendment, criteria for continued use of 80 mg simvastatin were modified and new increases of simvastatin dose to 80 mg were stopped).
    Other Names:
    • Vytorin
    • Inegy
  • Drug: simvastatin
    Simvastatin 40 mg per day from randomization through the end of participation. As per the original protocol, if LDL-C response was inadequate, the dose of simvastatin in the VYTORIN arm or simvastatin arm, could be increased to 80 mg (Note: per June 2011 protocol amendment, criteria for continued use of 80 mg simvastatin were modified and new increases of simvastatin dose to 80 mg were stopped).
    Other Name: Zocor
  • Drug: Placebo for simvastatin 40 mg
    one or two tablets orally daily
  • Drug: Placebo for ezetimibe 10 mg/simvastatin 40 mg combination
    one tablet orally daily.
Study Arms  ICMJE
  • Experimental: ezetimibe/simvastatin
    One Ezetimibe 10 mg/simvastatin 40 mg combination tablet and two simvastatin 40 mg placebo tablets once per day.
    Interventions:
    • Drug: ezetimibe/simvastatin
    • Drug: Placebo for simvastatin 40 mg
  • Active Comparator: simvastatin
    One simvastatin 40 mg tablet, one ezetimibe/simvastatin combination 10/40 placebo tablet and one simvastatin 40 mg placebo tablet once per day.
    Interventions:
    • Drug: simvastatin
    • Drug: Placebo for simvastatin 40 mg
    • Drug: Placebo for ezetimibe 10 mg/simvastatin 40 mg combination
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 28, 2015)
18144
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE September 18, 2014
Actual Primary Completion Date September 18, 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Clinically stable participants may be eligible to enroll within 10 days following hospital admission with high-risk acute coronary syndrome (either ST-elevation myocardial infarction [STEMI] or Non-STEMI or unstable angina)
  • Participants not taking a statin must have an LDL-C of 125 mg/dl or less. Participants taking a statin must have an LDL-C of 100 mg/dl or less.

Exclusion Criteria:

  • Pregnant or lactating woman, or intending to become pregnant
  • Participant with active liver disease or persistent unexplained serum transaminase elevation
  • History of alcohol or drug abuse
  • History of sensitivity to statin or ezetimibe
  • A participant for whom discontinuation of existing lipid lowering regimen poses an unacceptable risk.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries United States
 
Administrative Information
NCT Number  ICMJE NCT00202878
Other Study ID Numbers  ICMJE P04103
MK-0653A-080 ( Other Identifier: Merck Study Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP