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Effect of Sulodexide in Early Diabetic Nephropathy

This study has been completed.
Sponsor:
Collaborator:
Collaborative Study Group (CSG)
Information provided by (Responsible Party):
Keryx Biopharmaceuticals
ClinicalTrials.gov Identifier:
NCT00130208
First received: August 11, 2005
Last updated: September 7, 2012
Last verified: September 2012
  Purpose

The purpose of the study is to determine whether treatment with sulodexide is effective in reducing the level of urine albumin excretion in patients with early diabetic kidney disease expressed as microalbuminuria.


Condition Intervention Phase
Diabetic Nephropathy
Drug: Sulodexide
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: The Collaborative Study Group Trial: The Effect of Sulodexide in Patients With Type 2 Diabetes and Microalbuminuria

Resource links provided by NLM:


Further study details as provided by Keryx Biopharmaceuticals:

Primary Outcome Measures:
  • Conversion from microalbuminuria to normoalbuminuria [ Time Frame: 34 Weeks ] [ Designated as safety issue: No ]
    Run-in period, followed by a treatment period, followed by a Washout Period. Treatment period is 30 weeks and Washout Period 4 weeks.

  • Greater than 50% reduction in microalbuminuria [ Time Frame: 30 Weeks ] [ Designated as safety issue: No ]
    During the treatment period, KRX-101 is being compared to placebo to assess whether a 50% reduction in microalbuminuria has been achieved.


Secondary Outcome Measures:
  • Observed change in albumin excretion [ Time Frame: 34 Weeks ] [ Designated as safety issue: No ]
    Review of albumin excretion during the treatment period will be made and will also be compared to albumin excretion during the washout period.

  • Comparison of adverse events, laboratory parameters, and physical exams between active and placebo patients [ Time Frame: 34 weeks (also screening and run-in periods) ] [ Designated as safety issue: Yes ]
    Patients will be reviewed for adverse events, laboratory parameters, and physical examinations throughout the trial and compared by treatment arm (active v. placebo).


Enrollment: 1000
Study Start Date: August 2005
Study Completion Date: February 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sulodexide
Also known as KRX-101. All patients will be on standard of care ACE or ARBs.
Drug: Sulodexide
Placebo Comparator: Placebo
All patients will be on standard of care ACE or ARBs.

Detailed Description:

Diabetic nephropathy is an important cause of morbidity and mortality in patients with either type 1 or type 2 diabetes mellitus. The pathogenesis and natural history of diabetic nephropathy is characterized initially by microalbuminuria followed by a progressive decline in glomerular function. An emerging body of evidence supports the notion that glomerular capillary wall and mesangial alterations in diabetic nephropathy involve pathobiochemical alterations of glycoproteins in these structures. Evidence, in experimental animals rendered diabetic, reveals that the administration of heparin and other anionic glycoproteins (GAG) can effectively prevent the biochemical alterations which are responsible for albuminuria. Sulodexide, an orally active agent which does not have anticoagulant properties associated with its oral dose range, is comprised of three naturally occurring glycosaminoglycan (GAG) polysaccharide components isolated from porcine intestinal mucosa. Small clinical studies employing sulodexide, have shown that albuminuria is significantly diminished in patients with diabetic nephropathy, even when these patients are receiving angiotensin II receptor blockers (ARB) or angiotensin converting enzyme inhibitors (ACEI), agents already proven to reduce albuminuria and slow progressive diabetic nephropathy.

This study is designed to evaluate whether sulodexide is safe and effective in treating subjects with type 2 diabetic nephropathy. Subjects with type 2 diabetes and microalbuminuria (defined as a urinary albumin to creatinine ratio,(ACR)in men 35-200 mg/G and in women 45-200 mg/G) who are also receiving either irbesartan 300 mg/day, losartan 100 mg/day, or a maximum approved dose of an angiotensin receptor blocker (ARB) or angiotensin converting enzyme inhibitor (ACEI) will be enrolled in the study. The study will consist of the following periods:

  • Screening: of 1-2 weeks for assessing basic eligibility/exclusion criteria
  • Run-in: of up to 16 weeks on maximal dose of ARB or ACE with stable blood pressure control
  • Qualifying visit: qualifying patients are on maximal dose of ARB or ACE for a minimum of 4 months with stable BP control, SBP <150 mmHg, DBP <90 mmHg and albumin to creatinine ratio, (ACR) between in men 35-200 mg/G and in women 45-200 average of 3 first morning voids
  • Randomization: patients are randomized to sulodexide 100 mg or matching placebo administered orally twice a day.
  • Maintenance: 26 week maintenance period, with 4 visits to monitor safety and ACR
  • Washout Period: 8 week washout period, with 2 visits to monitor safety and ACR
  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
  • Serum creatinine equal to or less than 1.5 mg/dL
  • Microalbuminuria, defined by a urine albumin/creatinine ratio in men; 35- 200 mg albumin/G creatinine, in women; 45-200 mg albumin/G creatinine
  • Blood pressure controlled to less than 150/90 mmHg
  • Willing to change antihypertensive medication regimen if necessary

Exclusion Criteria:

  • Age of onset of type 2 diabetes <18 years;
  • HbA1C >10.0%;
  • Morbid obesity defined as a body mass index (BMI) >= 45 kg/m2;
  • Type 1 (insulin-dependent; juvenile onset) diabetes;
  • Renal disease as follows:

    • Patients with known non-diabetic renal disease
    • Renal allograft
  • Absolute requirement for combination therapy of angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB);
  • 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 or stent placement within 3 months of study entry;
    • Transient ischemic attack within 3 months of study entry;
    • Cerebrovascular accident within 3 months of study entry;
    • Symptomatic heart failure requiring ACE inhibition;
    • New York Heart Association Functional Class III or IV heart failure;
    • Obstructive valvular heart disease or hypertrophic cardiomyopathy;
    • 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);
  • History of multiple drug allergies;
  • 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;
  • Inability to remain on a stable dose of the following class of medications 30 days prior to randomization and throughout the study:

    • 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins);
    • Peroxisome proliferator-activated receptor gamma (PPAR gamma inhibitors (glitazones);
    • Cyclooxygenase-2 inhibitors (COX-2 inhibitors); or
    • Non-steroidal anti-inflammatory drugs (NSAIDS);
  • History of alcohol or other drug abuse within 12 months of study entry;
  • Known human immunodeficiency virus (HIV) 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 or liver transaminase (AST or ALT) >3 times upper limit of normal;
  • Anticipated surgery within trial period;
  • Inability to cooperate with study personnel or history of noncompliance to medical regimen (i.e., patients who would be expected to comply poorly with treatment);
  • Known allergies or intolerance to any heparin-like compound;
  • Untreated urinary tract infection that would impact urinary protein values; or
  • Prior exposure to sulodexide, either in a clinical setting or as a participant in another clinical study.
  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: NCT00130208

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, M.D. 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 by Keryx Biopharmaceuticals

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Keryx Biopharmaceuticals
ClinicalTrials.gov Identifier: NCT00130208     History of Changes
Other Study ID Numbers: KRX-101-301
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
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
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Keryx Biopharmaceuticals:
Diabetes
Diabetes Mellitus, Type 2
Albuminuria
Diabetic Nephropathy

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

ClinicalTrials.gov processed this record on November 25, 2014