Effect of Sulodexide on Albuminuria in Chinese Type 2 Diabetic Patients

Study Overview
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Brief Summary
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Current therapies targeting albuminuria in diabetic nephropathy leave residual urinary albumin secretion, which meanwhile leave residual cardiovascular risk. Previous studies demonstrated that sulodexide could reduce albuminuria in type 2 diabetic patients. But no data concerning Chinese population is available. The investigators aim to provide evidence of effects of sulodexide on diabetic nephropathy in Chinese diabetic patients. Further the investigators also test the hypothesis that sequential administration of intravenous and oral replacement of the drug would gain an earlier and greater reduction of albuminuria, compared with oral use only.

Official Title
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Effect of Intravenous and Oral Therapy With Sulodexide on Albuminuria in Type 2 Diabetic Patients

Conditions
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Diabetic Nephropathy, Albuminuria

Intervention / Treatment
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* Drug: intravenous use of sulodexide followed by oral use
* Drug: use of sulodexide orally only


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of type 2 diabetes based on WHO criteria Age 18-75 years old Serum creatinine ≤ 1.5 mg/dL (130umol/L) Albuminuria defined by a urine albumin/creatinine ratio(ACR) according to ADA criteria 2009 (microalbuminuria by 30-299 ug albumin/mg creatinine and macroalbuminuria by ≥300 ug albumin/mg creatinine on random spot urine collection ) Continued stable seated systolic blood pressure < 180 mmHg and diastolic blood pressure < 110 mmHg Willing to change antihypertensive medication regimen if necessary Willing to provide written informed consent to participate in the study Willing to take contraception,or infertility for the duration of the study Exclusion Criteria: Type 1 diabetes mellitus Present acute diabetic complication, or severe chronic diabetic complication(e.g. proliferative diabetic retinopathy) Complicating uncontrolled severe infection Hepatic insufficiency or renal insufficiency or severe disturbance of lipid metabolism Blood pressure ≥ 180/110mmHg Severe concomitant systemic disease(e.g. cardiac insufficiency, stroke), anticipated to be unable to finish the trial Uncooperative,unable to follow up, or anticipated unable to finish the trial Patients with other known specific renal diseases Untreated urinary tract infection that would impact urinary protein values Evidence of hepatic dysfunction including total bilirubin > 2.0 mg/dL (34 mmol/L) or elevated transaminases History of Cardiovascular disease as follows: Unstable angina pectoris, myocardial infarction, transient ischemic attack, cerebrovascular accident, New York Heart Association Functional Class III or IV heart failure, obstructive valvular heart disease or hypertrophic cardiomyopathy Any risk of bleeding, or platelet count < 100×109/L or anticipated surgery within research period Active, recurrent or metastatic cancer, or known HIV infection Participant in any experimental drug study in the past 90 days prior to the enrollment of the study, or plan to participate in any drug study during the study period Prior exposure to sulodexide, either in a clinical setting or as a participant in another clinical study Known allergy or intolerance to any heparin-like compounds or multiple drug allergies Lactation, pregnancy, or an anticipated or planned pregnancy during the study period Inability to give an informed consent or to cooperate with researchers (e.g. psychiatric disorder) or history of noncompliance to medical regimen

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: sequencial use of sulodexide<br>Patients will be given sulodexide 1200 LSU per day intravenously for 2 weeks. Then patients will receive 1000 LSU per day orally for 50 weeks. | Drug: intravenous use of sulodexide followed by oral use<br>* Patients will be given sulodexide 1200 LSU per day intravenously for 2 weeks,then receive 1000 LSU per day orally for 50 weeks.<br>* Other names: sequential use of sulodexide;|
| Active Comparator: oral use of sulodexide<br>Patients allocated to oral group will received 1000 LSU per day orally for 52 weeks | Drug: use of sulodexide orally only<br>* Patients receive 1000 LSU per day orally for 52 weeks<br>* Other names: oral use of sulodexide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in urine albumin/creatinine ratio | conversion to normoalbuminuria and at least a 25% reduction in UACR opposed to baseline, or 50% reduction in UACR opposed to baseline | 52th week since the commence of therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in urine albumin/creatinine ratio and serum creatinine |  | before and 2nd,12th,24th,36th and 60th week since the commence of therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetic nephropathy, albuminuria, type 2 diabetes, sulodexide