The Use of Cilostazol in Patients With Diabetic Nephropathy
A Randomised, Double-Blind, Placebo-Controlled Study of Cilostazol 100 mg Twice Daily in the Treatment of Diabetic Nephropathy in Hong Kong Chinese
Patients with type 2 diabetes have a long duration of disease for the development of complications. Among all complications, microangiopathic complications are major causes of mortality and morbidity in diabetic patients. In Asia, patients with type 2 diabetes are particularly susceptible to the development of kidney disease. Patients with diabetic kidney disease have more adverse metabolic profiles and increased risk of having other complications such as blindness, stroke, heart attack and nerve damage than those without. Despite receiving the best of care, the combined event rate of death, cardiovascular disease and end stage kidney disease in diabetic patients with renal impairment remained as high as 10% per year.
Cilostazol reduces platelet aggregation and prevents formation of blood clots. Furthermore, cilostazol treatment has been shown to reduce serum triglyceride concentrations and increase HDL-cholesterol levels. In this randomized placebo-controlled, double-blinded study, the investigators hypothesize that Cilostazol may reduce the rate of decline in renal function in Chinese patients with type 2 diabetes and mild to moderate renal impairment. Sixty patients will be randomised to receive either Cilostazol 100 mg twice daily or placebo for 12 months. The effect of Cilostazol on the progression of diabetic nephropathy, as defined by rates of decline in glomerular filtration rate, serum creatinine and urinary albumin excretion rate will be measured. The results will provide additional insight on the management of diabetic kidney disease which is prevalent among Chinese diabetic patients in Hong Kong.
研究概览
详细说明
Hypothesis:
Cilostazol reduces the rate of decline in renal function in Chinese patients with type 2 diabetes and mild to moderate renal impairment secondary to diabetic nephropathy.
Objectives:
To assess the suppressive effect of Cilostazol on the progression of diabetic nephropathy, as defined by rates of decline in glomerular filtration rate, serum creatinine and urinary albumin excretion rate.
The rising prevalence of diabetes in Asia imposes a heavy burden on the health care system. Given the increasingly early onset of disease, patients with type 2 diabetes have long duration of disease for the development of complications. Among all complications, microangiopathic complications are major causes of mortality and morbidity in diabetic patients. In Asia, patients with type 2 diabetes are particularly susceptible to the development of nephropathy. Among dialysis patients, the primary disease is diabetic nephropathy in about 40 to 50 % of patients. Despite the inhibition of the renin angiotensin system using either ACE inhibitor or AII receptor blocker (ARB) as well as introduction of tight glycaemic and blood pressure control, the prevalence of diabetic nephropathy remains high. More importantly, patients with nephropathy have more adverse metabolic profiles and increased risk of having other complications such as retinopathy, macrovascular diseases and neuropathy than those without. Indeed, according to the RENAAL Study, despite receiving the best of care, the combined event rate of death, cardiovascular disease and end stage renal disease in diabetic patients with renal impairment remained as high as 10% per year.
Cilostazol exerts antiplatelet, antithrombotic and vasodilating effects by inhibiting phosphodiesterase type 3 in platelets and vascular smooth muscle cells. Furthermore, cilostazol treatment has been shown to reduce serum triglyceride concentrations and increase HDL-cholesterol levels. In Japanese patients with type 2 diabetes, cilostazol therapy was associated with regression of carotid intimal media thickness and could prevent the onset of silent brain infarction. On the other hand, abnormal metabolism of prostaglandins in renal glomeruli has been postulated to modulate renal haemodynamics. Elevated levels of platelet-derived microparticles and soluble adhesion molecules may further contribute to the development of diabetic nephropathy. Cilostazol treatment had been shown to reduce serum levels of PMP, activated platelet subsets, soluble adhesion molecules and urinary excretion of thromboxane B2 in patients with type 2 diabetes. These changes were accompanied by a reduction in urinary albumin excretion and an increase in creatinine clearance.
研究类型
注册 (实际的)
阶段
- 第四阶段
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Male or female patients aged between 20 and 70 years
- Patients with Type 2 diabetic mellitus
- A fasting urinary albumin/creatinine ratio greater than or equal to 30 mg/mmol or 24 hour urinary albumin excretion greater than or equal to 300 mg/day in two urine collections during the baseline period
Two consecutive serum creatinine levels during baseline period which meet the following requirements:
- Women: between 80 umol/l and 250 umol/l (inclusive)
- Men: between 105 umol/l and 250 umol/l (inclusive)
- Written informed consent
Exclusion Criteria:
- Pregnancy
- Known allergy to cilostazol or aspirin
- Congestive heart failure (NYHA class III to IV)
- Severe liver impairment (greater than or equal to 3 times ULN of ALT)
- Serum potassium levels greater than or equal to 5.5 mmol/l on 2 consecutive specimens
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:并行分配
- 屏蔽:四人间
武器和干预
参与者组/臂 |
干预/治疗 |
---|---|
安慰剂比较:安慰剂
|
每天两次,每次 1 片
|
有源比较器:Cilostazol
Cilostazol 100 mg twice daily
|
西洛他唑 100 毫克,每日两次
其他名称:
|
研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
---|---|
Doubling of serum creatinine level
大体时间:1 year
|
1 year
|
50% reduction in GFR (estimated by MDRD equation)
大体时间:1 year
|
1 year
|
GFR less than 15 ml/min/1.73m2
大体时间:1 year
|
1 year
|
Need for dialysis
大体时间:1 year
|
1 year
|
Death related to renal causes
大体时间:1 year
|
1 year
|
Fatal or severe bleeding
大体时间:1 year
|
1 year
|
次要结果测量
结果测量 |
大体时间 |
---|---|
Composite cardiovascular endpoints (acute myocardial infarction, revascularisation procedures, heart failure or unstable angina or arrhythmia) requiring hospital admissions, lower extremity amputation)
大体时间:1 year
|
1 year
|
Number of hospital admissions, total number of days of hospital stay and attendance at the Accident and Emergency Department
大体时间:1 year
|
1 year
|
合作者和调查者
调查人员
- 首席研究员:Peter C Tong, PhD, MBBS、Chinese University of Hong Kong
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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