Effect of Sulodexide in Overt Diabetic Nephropathy
The purpose of this study is to determine whether sulodexide is effective in slowing or preventing the progression of diabetic kidney disease.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||The Collaborative Study Group Trial: The Effect of Sulodexide in Overt Type 2 Diabetic Nephropathy|
- Time to doubling of the serum creatinine or end stage kidney disease (ESRD) [ Time Frame: Time in study depended on time to doubling of serum creatinine ] [ Designated as safety issue: No ]Time in study depended on time to doubling of serum creatinine and when the patient was enrolled in the trial.
- Safety and tolerance of sulodexide therapy long-term [ Time Frame: Time in study depended on time to doubling of serum creatinine ] [ Designated as safety issue: Yes ]Review of laboratory parameters, adverse events, physical examinations, etc. were made to evaluate patient safety.
- Change in urinary protein/albumin excretion [ Time Frame: Time in study depended on time to doubling of serum creatinine ] [ Designated as safety issue: No ]Review of urinary protein and albumin excretion was made as an additional assessment of kidney function.
|Study Start Date:||August 2005|
|Study Completion Date:||March 2008|
|Primary Completion Date:||March 2008 (Final data collection date for primary outcome measure)|
Also known as KRX-101. These patients are also on standard of care ACEs and ARBs.
Other Name: KRX-101
Placebo Comparator: Placebo
These patients were on standard of care ACEs and ARBs.
Diabetes is now the most common cause of end-stage renal disease (ESRD) in the U.S. and in many other developed nations. Diabetic nephropathy now represents 44% of all new cases of ESRD in the U.S. Despite advances in clinical care, including improvements in glycemic and blood pressure control, the number of new cases of diabetes related ESRD continues to rise. In particular, the incidence of type 2 diabetes mellitus (DM2)-related cases of ESRD is rapidly increasing. From 1993 to 1997, 71% of all diabetes-related ESRD was attributable to DM2 (USRDS 1999). The earliest sign of diabetic kidney disease presents as microalbuminuria, the spilling of small of amounts of blood protein into the urine. Microalbuminuria correlates directly with the subsequent development of more advanced kidney disease. Improved glycemic control and blood pressure control with the use of inhibitors of the renin-angiotensin-aldosterone system can reduce the level of microalbuminuria and overt proteinuria. However, despite these measures, diabetic nephropathy continues to progress, albeit more slowly. Sulodexide belongs to a class of drugs called glycosaminoglycans (GAG). GAG therapy has been shown in animal models to prevent and or induce regression of albuminuria, and the morphologic changes associated with progressive diabetic nephropathy such as glomerular basement thickening, loss of the anionic charge density and mesangial collagen deposition. Sulodexide is approved in Europe to treat vascular indications. It has been utilized in several small phase II studies to treat early diabetic nephropathy, inducing an additional 40-70 % reduction in albuminuria in subjects whose albumin excretion was already reduced with tight glycemic control plus the use of inhibitors of the renin-angiotensin-aldosterone system for blood pressure control.
The purpose of this study is to add to this body of evidence that Sulodexide may offer additional benefit in preventing or ameliorating more advanced diabetic nephropathy manifested as overt proteinuria and reduced GFR. Subjects with type 2 diabetes, moderately elevated serum creatinine and overt proteinuria will be treated with a standardized maximal recommended/tolerated dose of irbesartan 300 mg/day or losartan 100 mg/day plus additional concomitant non-ARB, non-ACEi antihypertensive drugs,for up to 2-3 months to establish adequate and stable blood pressure control and urine protein excretion. After establishing baseline serum creatinine and urine protein excretion they will be randomized to either Sulodexide 200 mg/d or matching placebo. Subjects will be seen every 3 months to monitor safety and efficacy parameters for up to 4 years. The primary outcome is a doubling of baseline serum creatinine (50% loss of kidney function) or end stage kidney disease (ESRD).
|United States, Illinois|
|The Collaborative Study Group, Clinical Coordinating Center for U.S. and Canadian clinics, Rush University Medical Center|
|Chicago, Illinois, United States, 60612|
|The Collaborative Study Group, Clinical Coordinating Center for the Pacific Region, Monash Medical Center|
|Clayton / Melbourne, Victoria, Australia, 3168|
|The Collaborative Study Group, Clinical Coordinating Center for European Clinics, University of Groningen|
|Groningen, Netherlands, 9713 AV|
|Study Director:||Edmund J Lewis, MD||The Collaborative Study Group, Rush University Medical Center, Chicago, IL USA|
|Principal Investigator:||Robert C Atkins, M.D.||The Collaborative Study Group, Monash Medical Center, Clayton, Victoria, AUSTRALIA|
|Principal Investigator:||Dick deZeeuw, M.D.||The Collaborative Study Group, University of Groningen, NETHERLANDS|
|Principal Investigator:||Itamar Raz, M.D.||The Collaborative Study Group, Hadassah University, Jerusalem, ISRAEL|