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

Diabetic Nephropathy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01252056
• Other study ID #: 260-09-805-01
• Status: Completed
• Phase: Phase 4
• First received: April 21, 2010
• Last updated: May 7, 2013
• Start date: March 2010
• Est. completion date: December 2012

Study information

• Verified date: May 2013
• Source: Otsuka Beijing Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 353
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 75 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetic Nephropathies
• Diabetic Nephropathy
• Kidney Diseases

Intervention

Drug:
• Probucol
250mg,Bid
• Probucol and Cilostazol
50-100mg,Bid

Locations

Country	Name	City	State
China	Beijing Universuty First Hospital	Beijng	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Otsuka Beijing Research Institute

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	IMT	After 48-week and 96-week treatment, compare the change value of IMT from the baseline among 3 modality groups.	48 and 96W	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes