Diabetic NephropathyPhase 3NCT00130208
Effect of Sulodexide in Early Diabetic Nephropathy
A Phase 3 study testing Sulodexide in people with Diabetic Nephropathy, run by Keryx Biopharmaceuticals at 3 sites in 3 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Nephropathy
- What is being tested?
- Sulodexide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,056 participants
- Where
- 3 sitesin 3 countries
- Study dates
- Aug 2005to Feb 2008
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 37Show fewer
- 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.
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
United States1 site
The Collaborative Study Group, Clinical Coordinating Center for U.S. and Canadian Clinics, Rush University Medical Center
Chicago, Illinois, 60612
Australia1 site
The Collaborative Study Group, Clinical Coordinating Center for the Pacific Region, Monash Medical Center
Melbourne, Victoria, 3168
Netherlands1 site
The Collaborative Study Group, Clinical Coordinating Center for European Clinics, University of Groningen
Groningen, 9713 AV
About this study
Official title: The Collaborative Study Group Trial: The Effect of Sulodexide in Patients With Type 2 Diabetes and Microalbuminuria
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.
Read the 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
- Conditions
- Diabetic Nephropathy
- Being tested
- Sulodexide, Placebo
- Keywords
- Diabetes, Diabetes Mellitus, Type 2, Albuminuria, Diabetic Nephropathy
- Medical subject headings
- Diabetic Nephropathies, Diabetes Mellitus, Diabetes Mellitus, Type 2, Albuminuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SulodexideDrug
Also called KRX-101
100 mg sulodexide gelcaps
PlaceboDrug
Also called Placebo oral gelcap
0 mg gelcap
| Study group | Role | What they receive |
|---|---|---|
| Sulodexide | Experimental | Also known as KRX-101. All patients will be on standard of care ACE or ARBs. Receives: Drug: Sulodexide |
| Placebo | Placebo comparator | All patients will be on standard of care ACE or ARBs. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Conversion From Microalbuminuria to Normoalbuminuria
The primary efficacy variable was the fraction of those patients in the ITT population with valid baseline and Week 26 ACRs in whom "therapeutic success" was achieved at Week 26 measured as a conversion of microalbuminuria to normoalbuminuria and at least a 25% reduction in ACR relative to baseline
Measured: 26 Weeks
Number of Subjects With Greater Than 50% Reduction in Microalbuminuria
During the treatment period, KRX-101 is being compared to placebo to assess whether a 50% reduction in microalbuminuria has been achieved.
Measured: 26 Weeks
Secondary outcomes (1)
Change in Serum Albumin From Baseline to End of 26 Weeks
Measured: 26 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2005 (estimated)
- Study startAug 2005
- Primary completionJan 2008
- Study completionFeb 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetic NephropathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 1,056 participants (actual)
Sponsor and investigators
- Lead sponsor
- Keryx Biopharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Collaborative Study Group (CSG)
- Responsible party
- Sponsor
- Investigators
- Edmund J Lewis, M.D., Study director, The Collaborative Study Group, Rush University Medical Center, Chicago, IL USARobert C Atkins, M.D., Principal investigator, The Collaborative Study Group, Monash Medical Center, Clayton, Victoria, AUSTRALIADick deZeeuw, M.D., Principal investigator, The Collaborative Study Group, University of Groningen, NETHERLANDSItamar Raz, M.D., Principal investigator, The Collaborative Study Group, Hadassah University, Jerusalem, ISRAEL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00130208
- Sponsor's protocol ID
- KRX-101-301
- Status last verified
- Feb 2018
- First submitted
- 11 Aug 2005
- Last updated
- 23 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Lewis EJ, Lewis JB, Greene T, Hunsicker LG, Berl T, Pohl MA, de Zeeuw D, Heerspink HL, Rohde RD, Atkins RC, Reutens AT, Packham DK, Raz I; Collaborative Study Group. Sulodexide for kidney protection in type 2 diabetes patients with microalbuminuria: a randomized controlled trial. Am J Kidney Dis. 2011 Nov;58(5):729-36. doi: 10.1053/j.ajkd.2011.06.020. Epub 2011 Aug 26.
PubMed 21872376
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Collaborative Study Group Trial: The Effect of Sulodexide in Patients With Type 2 Diabetes and Microalbuminuria
- ClinicalTrials.gov ID
- NCT00130208
- Acronym / sponsor ID
- KRX-101-301
- Conditions
- Diabetic Nephropathy
- Keywords
- Diabetes, Diabetes Mellitus, Type 2, Albuminuria, Diabetic Nephropathy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,056 participants (actual)
- Lead sponsor
- Keryx BiopharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- Collaborative Study Group (CSG)
- Study start
- Aug 2005
- Primary completion
- Jan 2008 (actual)
- Study completion
- Feb 2008 (actual)
- First posted
- 15 Aug 2005 (estimated)
- Results
- Posted 23 Mar 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sulodexide | Experimental | Drug: SulodexideAlso known as KRX-101. All patients will be on standard of care ACE or ARBs. |
| Placebo | Placebo comparator | Drug: PlaceboAll patients will be on standard of care ACE or ARBs. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (37 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SulodexideAlso: KRX-101100 mg sulodexide gelcaps | Drug | Sulodexide |
| PlaceboAlso: Placebo oral gelcap0 mg gelcap | Drug | Placebo |
Primary outcome
Number of Subjects With Conversion From Microalbuminuria to Normoalbuminuria
Time frame: 26 Weeks
The primary efficacy variable was the fraction of those patients in the ITT population with valid baseline and Week 26 ACRs in whom "therapeutic success" was achieved at Week 26 measured as a conversion of microalbuminuria to normoalbuminuria and at least a 25% reduction in ACR relative to baseline
Number of Subjects With Greater Than 50% Reduction in Microalbuminuria
Time frame: 26 Weeks
During the treatment period, KRX-101 is being compared to placebo to assess whether a 50% reduction in microalbuminuria has been achieved.
1 secondary outcome
Change in Serum Albumin From Baseline to End of 26 Weeks
Time frame: 26 Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 21872376Lewis EJ, Lewis JB, Greene T, Hunsicker LG, Berl T, Pohl MA, de Zeeuw D, Heerspink HL, Rohde RD, Atkins RC, Reutens AT, Packham DK, Raz I; Collaborative Study Group. Sulodexide for kidney protection in type 2 diabetes patients with microalbuminuria: a randomized controlled trial. Am J Kidney Dis. 2011 Nov;58(5):729-36. doi: 10.1053/j.ajkd.2011.06.020. Epub 2011 Aug 26.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Edmund J Lewis, M.D. study director
The Collaborative Study Group, Rush University Medical Center, Chicago, IL USA
Robert C Atkins, M.D. principal investigator
The Collaborative Study Group, Monash Medical Center, Clayton, Victoria, AUSTRALIA
Dick deZeeuw, M.D. principal investigator
The Collaborative Study Group, University of Groningen, NETHERLANDS
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sulodexide in people with Diabetic Nephropathy, run by Keryx Biopharmaceuticals at 3 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States, Australia, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Mar 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects With Conversion From Microalbuminuria to Normoalbuminuria (time frame: 26 Weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00130208, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2018.