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)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 18,144
- 主要终点
- 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)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
ezetimibe/simvastatin
One Ezetimibe 10 mg/simvastatin 40 mg combination tablet and two simvastatin 40 mg placebo tablets once per day.
干预措施: ezetimibe/simvastatin (Drug)
ezetimibe/simvastatin
One Ezetimibe 10 mg/simvastatin 40 mg combination tablet and two simvastatin 40 mg placebo tablets once per day.
干预措施: Placebo for simvastatin 40 mg (Drug)
simvastatin
One simvastatin 40 mg tablet, one ezetimibe/simvastatin combination 10/40 placebo tablet and one simvastatin 40 mg placebo tablet once per day.
干预措施: simvastatin (Drug)
simvastatin
One simvastatin 40 mg tablet, one ezetimibe/simvastatin combination 10/40 placebo tablet and one simvastatin 40 mg placebo tablet once per day.
干预措施: Placebo for simvastatin 40 mg (Drug)
simvastatin
One simvastatin 40 mg tablet, one ezetimibe/simvastatin combination 10/40 placebo tablet and one simvastatin 40 mg placebo tablet once per day.
干预措施: Placebo for ezetimibe 10 mg/simvastatin 40 mg combination (Drug)
结局指标
主要结局
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)
时间窗: 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.
次要结局
- 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)(Up to approximately 9 years)
- 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)(Up to approximately 9 years)
- 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)(Up to approximately 9 years)