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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Otsuka Beijing Research Institute
ClinicalTrials.gov Identifier:
NCT01252056
First received: April 21, 2010
Last updated: May 7, 2013
Last verified: May 2013
  Purpose

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


Condition Intervention Phase
Diabetic Nephropathy
Drug: Probucol
Drug: Probucol and Cilostazol
Phase 4

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

Resource links provided by NLM:


Further study details as provided by Otsuka Beijing Research Institute:

Primary Outcome Measures:
  • nephropathy development [ Time Frame: 96W ] [ Designated as safety issue: No ]
    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 [ Time Frame: 48 and 96W ] [ Designated as safety issue: No ]
    After 48-week and 96-week treatment, compare the change value of IMT from the baseline among 3 modality groups.

  • Atherosclerosis related biomarkers [ Time Frame: 48 and 96W ] [ Designated as safety issue: No ]
    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 [ Time Frame: 48 and 96W ] [ Designated as safety issue: No ]
    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 [ Time Frame: 96W ] [ Designated as safety issue: Yes ]
    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


Enrollment: 353
Study Start Date: March 2010
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   40 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01252056

Locations
China, Beijing
Beijing Universuty First Hospital
Beijng, Beijing, China
Sponsors and Collaborators
Otsuka Beijing Research Institute
Investigators
Principal Investigator: Xiaohui Guo Beijing University First Hospital
  More Information

No publications provided

Responsible Party: Otsuka Beijing Research Institute
ClinicalTrials.gov Identifier: NCT01252056     History of Changes
Other Study ID Numbers: 260-09-805-01
Study First Received: April 21, 2010
Last Updated: May 7, 2013
Health Authority: China: Food and Drug Administration

Additional relevant MeSH terms:
Diabetic Nephropathies
Kidney Diseases
Urologic Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Probucol
Cilostazol
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Antioxidants
Protective Agents
Physiological Effects of Drugs
Fibrinolytic Agents
Fibrin Modulating Agents
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Vasodilator Agents
Neuroprotective Agents
Central Nervous System Agents
Phosphodiesterase 3 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Bronchodilator Agents

ClinicalTrials.gov processed this record on July 20, 2014