A Randomized, Prospective, Double-Blind Study to Evaluate the Effects on Lipid Profile of Combined Ezetimibe and Simvastatin Therapy as Compared to Simvastatin Alone in People With Type 2 Diabetes
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 108
- 试验地点
- 8
- 主要终点
- LDL-cholesterol, at 16 weeks of treatment. LDL-cholesterol is measured at -4, 0, 8, 12 and 16 weeks.
研究概览
简要总结
Diabetes mellitus is becoming a global epidemic burden. Its chronic cardiovascular complications, myocardial infarction and stroke, are the main causes of death in diabetic patients. It was found that low density lipoprotein (LDL) cholesterol concentration is related to the increased coronary disease risk that could be successfully reduced by cholesterol-lowering therapy. Furthermore, preliminary evidence suggests that ameliorating dyslipidemia may be renoprotective in diabetic patients with proteinuria.
Ezetimibe is the first selective inhibitor of cholesterol absorption and it has demonstrated a high efficacy in lowering cholesterol concentration and an excellent safety profile. Preliminary data suggest that ezetimibe, combined with a drug that blocks the cholesterol synthesis (statins), could be even more effective in decreasing cholesterol concentration. The aim of this study is to evaluate whether ezetimibe-simvastatin combined therapy is superior to simvastatin monotherapy in ameliorating the lipid profile and albuminuria in type 2 diabetic patients.
详细描述
INTRODUCTION
Diabetes mellitus contributes substantially to the global burden of disease, with an estimated 150 million people affected worldwide and its prevalence is expected to double by 2025. Myocardial infarction and stroke are common causes of major morbidity in people with diabetes, most of whose deaths are attributed to cardiovascular causes. Recent findings provide definitive evidences that cholesterol-lowering therapy can produce substantial reductions in the risk of heart attacks, stroke and revascularizations in diabetic patients even if they do not have high blood cholesterol concentrations.
Also preliminary evidence is available that ameliorating dyslipidemia may be renoprotective in diabetic patients with proteinuria.
Ezetimibe is the first member of a class of highly selective cholesterol absorption inhibitors that effectively and potently prevents the absorption of cholesterol by inhibiting the passage of biliary and dietary cholesterol across the wall of the small intestine, without affecting absorption of other fat-soluble nutrients.
Many pre-clinical models have demonstrated the lipid-lowering and anti-atherosclerotic properties of ezetimibe as a single agent, and showed its synergistic effect in combination with HMGCoA reductase inhibitors (statins).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Double
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type 2 diabetes mellitus with stable antidiabetic treatment since at least three months
- •Total cholesterol concentrations >135mg/dl and/or concomitant lipid lowering therapy with HMGCoA inhibitors
- •Serum creatinine ≤1.5mg/dl
- •Urinary albumin excretion rate < 200μg/min
- •Written informed consent
排除标准
- •History of myocardial infarction, stroke or hospital admission for angina within the previous 6 months
- •History of percutaneous transluminal coronary angioplasty or coronary artery bypass grafting
- •Clinically manifest heart failure (grade III or above according to New York Heart Association criteria)
- •Poor glycemic control (HbA1C >11%)
- •Primary hyperlipidemia
- •Uncontrolled thyroid diseases
- •Infectious disease within 4 weeks of starting
- •Acute liver disease or hepatic dysfunction
- •Inflammatory muscle disease or evidence of muscle problems
- •Concurrent treatment with systemic steroids, androgens, cyclosporin and other immunosuppressive drugs, fibrates, high-dose niacin or cholestyramine
- •Pregnancy or lactating
- •Women of childbearing potential without following a scientifically accepted form of contraception
- •Life-threatening conditions or terminal concomitant diseases other than diabetes
- •Specific contraindications or history of hypersensitivity to the study drugs or other statins
- •Legal incapacity and/or other circumstances rendering the patient unable to understand the nature, scope and possible consequence of the trial
- •Evidence of an uncooperative attitude
- •Any evidence that patient will not be able to complete the trial follow-up
结局指标
主要结局
LDL-cholesterol, at 16 weeks of treatment. LDL-cholesterol is measured at -4, 0, 8, 12 and 16 weeks.
次要结局
- Total cholesterol, apolipoprotein A1 and B, lipoprotein and triglycerides, at -4, 0, 8, 12 and 16 weeks
- Explorative
- Urinary albumin excretion, at -4, 0, 8 and 16 weeks