A Clinical Study to Evaluate the Efficacy and Safety of Cilostazol and Probucol in Combination on Patients With Diabetic Nephropathy

A Randomized, Control, Parallel, Open Label, Multi-centre Clinical Study to Evaluate the Efficacy and Safety of Cilostazol and Probucol in Combination on Patients With Diabetic Nephropathy

The efficacy and safety of Cilostazol and Probucol in combination on patients with diabetic nephropathy is better than the single use.

Study Overview

• Status: Completed
• Conditions: Diabetic Nephropathy
• Intervention / Treatment: Drug: Probucol; Drug: Probucol and Cilostazol

Detailed Description

The objectives of this study is:

1. To evaluate the efficacy of Probucol on deferring nephropathy development of the patients with diabetic nephropathy (including: the change value of urine albumin from the baseline, the rate of the patients with serum creatinine reaching a doubling of the base-line serum creatinine, the rate of the hemodialysis-free survival).
2. To evaluate the efficacy of Cliostazol and Probucol in combination on deferring nephropathy development of the patients with diabetic nephropathy
3. To evaluate the efficacy of Cilostazol and Probucol in combination on atherosclerosis related biomarkers change. Atherosclerosis related biomarkers include:(a)Endothelium parameter: ICAM-1, vWF, VCAM-1,and McP-1. (b)Finolysis parameter: TM. (c)Inflammation parameter: Hs-CRP; IL-6. (d)Oxidation parameter: Ox-LDL, 8-OHdG. (e)Lipid parameter: TC, LDL-C, HDL-C, TG.
4. To evaluate the efficacy of Cilostazol and Probucol in combination on the progress of carotid intima-media thickness (IMT) on patients with diabetic nephropathy.
5. To evaluate the safety of Cilostazol and Probucol in combination on the patients with diabetic nephropathy.

• Study Type: Interventional
• Enrollment (Actual): 353
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijng, Beijing, China
      • Beijing Universuty First Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female age 40~75 years old
• Type 2 diabetes mellitus above 6 months
• HbA1c ≤8%
• Twice (above 2-week interval) confirmed urinary albumin at 30-3000µg/mg.cre
• Receive routine dosage ACEI or ARB treatment above 2 months, and the dosage has been fixed for at least 1 month
• LDL-C>100 mg/dL (2.60 mmol/L) and/ or hyperlipidemia patients with Statins treatment
• Free will to sign the informed consent form

Exclusion Criteria:

• Has an allergic history to investigational drugs
• Receive antilipemic agents (except Statins) within the latest 2 months, including Probucol
• Receive antiplatelet or anticoagulation agents (except Aspirin) within the latest 2 months, including Cilostazol
• Rapid progression of nephropathy within the latest 3 months
• Kidney disease caused by other reasons according to medical history
• Serum potassium level less than 3.5 mEq/L or more than 5.5 mEq/L
• Hemorrhagic tendency or hemorrhagic disease (such as alimentary tract hemorrhage, active fundus hemorrhage, etc.)
• Has a myocardial infarction, angina pectoris, or cerebral infarction within the latest 3 months
• Congestive heart failure
• Pregnant, potentially pregnant, or lactating woman
• Severe hepatic inadequacy (AST or ALT is 2.5 times higher than the upper limit of the normal value range)
• Serum creatinine level is 1.5 times higher than the upper limit of the normal value range
• Persistent or hardly controlled hypertension (such as malignant hypertension, SBP≥170 mmHg and/ or DBP≥100 mmHg)
• Severe ventricular arrhythmia (such as multiple and multifocal premature ventricular contractions)
• Has a medical history of cardiac syncope or primary syncope
• Has condition that may prolong QT interval (such as congenital long QT syndrome, taking drugs which prolong QT interval, hypokalemia or hypomagnesemia, etc.), or for man QT interval>450msec, for woman QT interval>470msec
• Has severe complication (such as diabetes mellitus ketoacidosis, nonketotic hyperosmolar diabetic coma, malignant tumor, severe anaemia, severe hematologic diseases, etc.)
• Register other clinical trials within the latest 3 months
• Other conditions that would be excluded from this study according to doctors'judgment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control
Active Comparator: Probucol; Probucol treatment	Drug: Probucol; 250mg,Bid
Active Comparator: Combination; Probucol and Cilostazol	Drug: Probucol and Cilostazol; 50-100mg,Bid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
nephropathy development	After 96-week treatment, compare the efficacy between Probucol group and group control group on deferring nephropathy development of the patients with diabetic nephropathy (including: the change value of urine albumin from the baseline, the rate of the patients with serum creatinine reaching a doubling of the base-line serum creatinine, the rate of the hemodialysis-free survival)	96W

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IMT	After 48-week and 96-week treatment, compare the change value of IMT from the baseline among 3 modality groups.	48 and 96W
Atherosclerosis related biomarkers	After 12-week, 48-week and 96-week treatment, compare the change value of atherosclerosis related biomarkers from the baseline among 3 modality groups	48 and 96W
Nephropathy development	1. After 48-week and 96-week treatment, compare the efficacy among 3 modality groups on deferring nephropathy development of the patients with diabetic nephropathy (including: the change value of urine albumin from the baseline, the rate of the patients with serum creatinine reaching a doubling of the base-line serum creatinine, the rate of the hemodialysis-free survival)	48 and 96W
Adverse events	Incidence of adverse events, clinically relevant abnormal laboratory results before and after treatment (including hemotology, biochemistry, routine urine analysis and glycosylated hemoglobin), abnormal findings of vital sign, physical examination, and 12-lead ECG results	96W

Collaborators and Investigators

• Sponsor: Otsuka Beijing Research Institute
• Investigators: Principal Investigator: Xiaohui Guo, Beijing University First Hospital

Publications and helpful links

General Publications

• Natale P, Palmer SC, Saglimbene VM, Ruospo M, Razavian M, Craig JC, Jardine MJ, Webster AC, Strippoli GF. Antiplatelet agents for chronic kidney disease. Cochrane Database Syst Rev. 2022 Feb 28;2(2):CD008834. doi: 10.1002/14651858.CD008834.pub4.

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: April 21, 2010
• First Submitted That Met QC Criteria: December 1, 2010
• First Posted (Estimate): December 2, 2010

Study Record Updates

• Last Update Posted (Estimate): May 8, 2013
• Last Update Submitted That Met QC Criteria: May 7, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Kidney Diseases; Diabetic Nephropathies; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Antimetabolites; Neuroprotective Agents; Protective Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Antioxidants; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Cilostazol; Probucol
• Other Study ID Numbers: 260-09-805-01