The Use of Cilostazol in Patients With Diabetic Nephropathy
Information source: Chinese University of Hong Kong
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Diabetes Mellitus, Type 2; Diabetes Complications
Intervention: Cilostazol (Drug); Placebo (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: Chinese University of Hong Kong Official(s) and/or principal investigator(s): Peter C Tong, PhD, MBBS, Principal Investigator, Affiliation: Chinese University of Hong Kong
Summary
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.
Clinical Details
Official title: A Randomised, Double-Blind, Placebo-Controlled Study of Cilostazol 100 mg Twice Daily in the Treatment of Diabetic Nephropathy in Hong Kong Chinese
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Doubling of serum creatinine level50% reduction in GFR (estimated by MDRD equation) GFR less than 15 ml/min/1.73m2 Need for dialysis Death related to renal causes Fatal or severe bleeding
Secondary outcome: Composite cardiovascular endpoints (acute myocardial infarction, revascularisation procedures, heart failure or unstable angina or arrhythmia) requiring hospital admissions, lower extremity amputation)Number of hospital admissions, total number of days of hospital stay and attendance at the Accident and Emergency Department
Detailed description:
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.
Eligibility
Minimum age: 20 Years.
Maximum age: 70 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Male or female patients aged between 20 and 70 years
2. Patients with Type 2 diabetic mellitus
3. 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
4. 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)
5. 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
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Additional Information
Starting date: December 2005
Last updated: May 21, 2009
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