Effect of Sulodexide in Overt Diabetic Nephropathy

This study has been terminated.
(No difference in protein excretion at 6&12 months. No safety issues.)
Sponsor:
Collaborator:
Collaborative Study Group (CSG)
Information provided by (Responsible Party):
Keryx Biopharmaceuticals
ClinicalTrials.gov Identifier:
NCT00130312
First received: August 11, 2005
Last updated: September 7, 2012
Last verified: September 2012
  Purpose

The purpose of this study is to determine whether sulodexide is effective in slowing or preventing the progression of diabetic kidney disease.


Condition Intervention Phase
Diabetic Nephropathy
Drug: Sulodexide
Phase 4

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Keryx Biopharmaceuticals:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 1248
Study Start Date: August 2005
Study Completion Date: March 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sulodexide
Also known as KRX-101. These patients are also on standard of care ACEs and ARBs.
Drug: Sulodexide
N/A
Other Name: KRX-101
Placebo Comparator: Placebo
These patients were on standard of care ACEs and ARBs.

Detailed Description:

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of type 2 diabetes;
  • Urine protein to creatinine ratio (PCR) equal to or greater than 900 mg/G (101.7 mg/mmol) in women and equal to or greater than 650 mg/G (73.45 mg/mmol) in men;
  • Serum creatinine in women 1.3 - 3.0 mg/dL (115-265 μmol/L), inclusive, and in men 1.5 - 3.0 mg/dL (133-265 μmol/L), inclusive;
  • Willing to discontinue antihypertensive medication regimen, if applicable;
  • Willing and able to give informed consent.

Exclusion Criteria:

  • Type 1 (insulin-dependent; juvenile onset) diabetes;
  • Renal disease as follows:

    • Patients with known non-diabetic renal disease (nephrosclerosis superimposed on diabetic nephropathy acceptable), or
    • Renal allograft;
  • Absolute requirement for combination therapy of angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB);
  • Patients who require ACEI, but not ACEI/ARB combination;
  • Cardiovascular disease as follows:

    • Unstable angina pectoris within 3 months of study entry;
    • Myocardial infarction, coronary artery bypass graft surgery, or percutaneous transluminal coronary angioplasty/stent within 3 months of study entry;
    • Transient ischemic attack within 3 months of study entry;
    • Cerebrovascular accident within 3 months of study entry;
    • New York Heart Association Functional Class III or IV (Note: if a patient is New York Heart Association Functional Class I or II and requires an ACEI, consult with the Clinical Coordinating Center to obtain permission for the patient to be on an ACEI rather than an ARB);
    • Obstructive valvular heart disease or hypertrophic cardiomyopathy; or
    • Second or third degree atrioventricular block not successfully treated with a pacemaker;
  • Need for chronic (>2 weeks) immunosuppressive therapy, including corticosteroids (excluding inhaled or nasal steroids);
  • New diagnosis of cancer or recurrent cancer within 5 years of screening (except non-melanoma skin cancer);
  • Psychiatric disorder that interferes with the patient's ability to comply with the protocol;
  • Inability to tolerate oral medication or a history of significant malabsorption;
  • History of alcohol or other drug abuse within 12 months of study entry;
  • Known human immunodeficiency virus disease;
  • Any other medical condition which renders the patient unable to or unlikely to complete the study, or which would interfere with optimal participation in the study or produce significant risk to the patient;
  • Receipt of any investigational drugs (including placebo) within 30 days of enrollment;
  • Evidence of hepatic dysfunction including total bilirubin >2.0 mg/dL (>35 micromol/L) or liver transaminase (aspartate aminotransferase [AST] or alanine transferase [ALT]) >3 times upper limit of normal;
  • Anticipate need for surgery;
  • Inability to cooperate with study personnel or history of noncompliance to medical regimen;
  • Known allergies or intolerance to any heparin-like compound including heparin-induced thrombocytopenia Type II;
  • Prior exposure to sulodexide, either in a clinical setting or as a participant in another clinical study.
  • Untreated urinary tract infection that would impact urinary protein values.
  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: NCT00130312

Locations
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
Australia, Victoria
The Collaborative Study Group, Clinical Coordinating Center for the Pacific Region, Monash Medical Center
Clayton / Melbourne, Victoria, Australia, 3168
Netherlands
The Collaborative Study Group, Clinical Coordinating Center for European Clinics, University of Groningen
Groningen, Netherlands, 9713 AV
Sponsors and Collaborators
Keryx Biopharmaceuticals
Collaborative Study Group (CSG)
Investigators
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
  More Information

No publications provided

Responsible Party: Keryx Biopharmaceuticals
ClinicalTrials.gov Identifier: NCT00130312     History of Changes
Obsolete Identifiers: NCT00342238
Other Study ID Numbers: KRX-101-401
Study First Received: August 11, 2005
Last Updated: September 7, 2012
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Federal Ministry for Health and Women
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Canada: Health Canada
Denmark: Danish Medicines Agency
Finland: Finnish Medicines Agency
France: Ministry of Health
Hong Kong: Department of Health
Hungary: National Institute of Pharmacy
Ireland: Irish Medicines Board
Israel: Israeli Health Ministry Pharmaceutical Administration
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Malaysia: Ministry of Health
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
New Zealand: Health and Disability Ethics Committees
Poland: Ministry of Health
Portugal: National Pharmacy and Medicines Institute
Singapore: Health Sciences Authority
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Switzerland: Swissmedic
Taiwan: Department of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Keryx Biopharmaceuticals:
Diabetes
Diabetic Nephropathy
Proteinuria

Additional relevant MeSH terms:
Diabetic Nephropathies
Kidney Diseases
Urologic Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Glucuronyl glucosamine glycan sulfate
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Cardiovascular Agents
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 26, 2014