Clinical trial NCT01252056: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetic Nephropathy
Lead sponsor: Otsuka Beijing Research Institute
Sponsor class: INDUSTRY
First posted: 2010-12-02
Enrollment: 353
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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:

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.

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

Primary outcomes:
measure: nephropathy development
timeFrame: 96W
Secondary outcomes:
measure: IMT
timeFrame: 48 and 96W
measure: Atherosclerosis related biomarkers
timeFrame: 48 and 96W
measure: Nephropathy development
timeFrame: 48 and 96W
measure: Adverse events
timeFrame: 96W
Other outcomes:
Locations:
city: Beijng
country: China
facility: Beijing Universuty First Hospital
state: Beijing
Study officials:
affiliation: Beijing University First Hospital
name: Xiaohui Guo
role: PRINCIPAL_INVESTIGATOR
References:
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.