A Clinical Study to Evaluate the Efficacy and Safety of Cilostazol and Probucol in Combination on Patients With Diabetic Nephropathy
Primary Purpose
Diabetic Nephropathy
Status
Completed
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Probucol
Probucol and Cilostazol
Sponsored by
About this trial
This is an interventional treatment trial for Diabetic Nephropathy
Eligibility Criteria
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
Sites / Locations
- Beijing Universuty First Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
No Intervention
Active Comparator
Active Comparator
Arm Label
Control
Probucol
Combination
Arm Description
Probucol treatment
Probucol and Cilostazol
Outcomes
Primary Outcome Measures
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)
Secondary Outcome Measures
IMT
After 48-week and 96-week treatment, compare the change value of IMT from the baseline among 3 modality groups.
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
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)
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
Full Information
NCT ID
NCT01252056
First Posted
April 21, 2010
Last Updated
May 7, 2013
Sponsor
Otsuka Beijing Research Institute
1. Study Identification
Unique Protocol Identification Number
NCT01252056
Brief Title
A Clinical Study to Evaluate the Efficacy and Safety of Cilostazol and Probucol in Combination on Patients With Diabetic Nephropathy
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2013
Overall Recruitment Status
Completed
Study Start Date
March 2010 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
December 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Otsuka Beijing Research Institute
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The efficacy and safety of Cilostazol and Probucol in combination on patients with diabetic nephropathy is better than the single use.
Detailed Description
The objectives of this study is:
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).
To evaluate the efficacy of Cliostazol and Probucol in combination on deferring nephropathy development of the patients with diabetic nephropathy
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.
To evaluate the efficacy of Cilostazol and Probucol in combination on the progress of carotid intima-media thickness (IMT) on patients with diabetic nephropathy.
To evaluate the safety of Cilostazol and Probucol in combination on the patients with diabetic nephropathy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Nephropathy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
353 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Control
Arm Type
No Intervention
Arm Title
Probucol
Arm Type
Active Comparator
Arm Description
Probucol treatment
Arm Title
Combination
Arm Type
Active Comparator
Arm Description
Probucol and Cilostazol
Intervention Type
Drug
Intervention Name(s)
Probucol
Intervention Description
250mg,Bid
Intervention Type
Drug
Intervention Name(s)
Probucol and Cilostazol
Intervention Description
50-100mg,Bid
Primary Outcome Measure Information:
Title
nephropathy development
Description
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)
Time Frame
96W
Secondary Outcome Measure Information:
Title
IMT
Description
After 48-week and 96-week treatment, compare the change value of IMT from the baseline among 3 modality groups.
Time Frame
48 and 96W
Title
Atherosclerosis related biomarkers
Description
After 12-week, 48-week and 96-week treatment, compare the change value of atherosclerosis related biomarkers from the baseline among 3 modality groups
Time Frame
48 and 96W
Title
Nephropathy development
Description
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)
Time Frame
48 and 96W
Title
Adverse events
Description
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
Time Frame
96W
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xiaohui Guo
Organizational Affiliation
Beijing University First Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing Universuty First Hospital
City
Beijng
State/Province
Beijing
Country
China
12. IPD Sharing Statement
Citations:
PubMed Identifier
35224730
Citation
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.
Results Reference
derived
Learn more about this trial
A Clinical Study to Evaluate the Efficacy and Safety of Cilostazol and Probucol in Combination on Patients With Diabetic Nephropathy
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