Diabetic NephropathyPhase 4NCT00130312
Effect of Sulodexide in Overt Diabetic Nephropathy
A Phase 4 study testing Sulodexide in people with Diabetic Nephropathy, run by Keryx Biopharmaceuticals at 3 sites in 3 countries.
Trial summary
The purpose of this study is to determine whether sulodexide is effective in slowing or preventing the progression of diabetic kidney disease. 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
- 968 participants
- Where
- 3 sitesin 3 countries
- Study dates
- Aug 2005to Mar 2008
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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;
- 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.
Who cannot join
- 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;
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- 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.
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 Overt Type 2 Diabetic Nephropathy
The purpose of this study is to determine whether sulodexide is effective in slowing or preventing the progression of diabetic kidney disease.
Read the 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).
- Conditions
- Diabetic Nephropathy
- Being tested
- Sulodexide, Placebo
- Keywords
- Diabetes, Diabetic Nephropathy, Proteinuria
- Medical subject headings
- Diabetic Nephropathies, Diabetes Mellitus, Proteinuria
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 gelcap in the morning and evening
PlaceboDrug
Also called placebo gelpcap
1 placebo gelcap in the morning and evening
| Study group | Role | What they receive |
|---|---|---|
| Sulodexide | Experimental | Also known as KRX-101. These patients are also on ACEs and ARBs (irbesartin and/or losartan). Receives: Drug: Sulodexide |
| Placebo | Placebo comparator | These patients are also on ACEs and ARBs (irbesartin and/or losartan). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to doubling of the serum creatinine or end stage kidney disease (ESRD)
Time in study depended on time to doubling of serum creatinine and when the patient was enrolled in the trial.
Measured: Time in study depended on time to doubling of serum creatinine
Safety and tolerance of sulodexide therapy long-term
Review of laboratory parameters, adverse events, physical examinations, etc. were made to evaluate patient safety.
Measured: Time in study depended on time to doubling of serum creatinine
Secondary outcomes (1)
Change in urinary protein/albumin excretion
Review of urinary protein and albumin excretion was made as an additional assessment of kidney function.
Measured: Time in study depended on time to doubling of serum creatinine
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 completionMar 2008
- Study completionMar 2008
Why it stopped: No difference in protein excretion at 6\&12 months. No safety issues.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 968 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, MD, 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
- NCT00130312
- Sponsor's protocol ID
- KRX-101-401
- Status last verified
- Mar 2021
- First submitted
- 11 Aug 2005
- Last updated
- 19 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Bidadkosh A, Lambooy SPH, Heerspink HJ, Pena MJ, Henning RH, Buikema H, Deelman LE. Predictive Properties of Biomarkers GDF-15, NTproBNP, and hs-TnT for Morbidity and Mortality in Patients With Type 2 Diabetes With Nephropathy. Diabetes Care. 2017 Jun;40(6):784-792. doi: 10.2337/dc16-2175. Epub 2017 Mar 24.
PubMed 28341782
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2021. 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 Overt Type 2 Diabetic Nephropathy
- ClinicalTrials.gov ID
- NCT00130312
- Acronym / sponsor ID
- KRX-101-401
- Conditions
- Diabetic Nephropathy
- Keywords
- Diabetes, Diabetic Nephropathy, Proteinuria
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: No difference in protein excretion at 6\&12 months. No safety issues.
- Enrolment
- 968 participants (actual)
- Lead sponsor
- Keryx BiopharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- Collaborative Study Group (CSG)
- Study start
- Aug 2005
- Primary completion
- Mar 2008 (actual)
- Study completion
- Mar 2008 (actual)
- First posted
- 15 Aug 2005 (estimated)
- Results
- Not posted in the source record
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 this study is to determine whether sulodexide is effective in slowing or preventing the progression of diabetic kidney disease.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sulodexide | Experimental | Drug: SulodexideAlso known as KRX-101. These patients are also on ACEs and ARBs (irbesartin and/or losartan). |
| Placebo | Placebo comparator | Drug: PlaceboThese patients are also on ACEs and ARBs (irbesartin and/or losartan). |
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;
- 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.
Key exclusion criteria (28 listed)
- Type 1 (insulin-dependent; juvenile onset) diabetes;
- Renal disease as follows:
- 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:
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 gelcap in the morning and evening | Drug | Sulodexide |
| PlaceboAlso: placebo gelpcap1 placebo gelcap in the morning and evening | Drug | Placebo |
Primary outcome
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
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
Review of laboratory parameters, adverse events, physical examinations, etc. were made to evaluate patient safety.
1 secondary outcome
Change in urinary protein/albumin excretion
Time frame: Time in study depended on time to doubling of serum creatinine
Results and safety
The study was stopped early (reason given: No difference in protein excretion at 6\&12 months. No safety issues.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2021.
- Derived from this study: PubMed 28341782Bidadkosh A, Lambooy SPH, Heerspink HJ, Pena MJ, Henning RH, Buikema H, Deelman LE. Predictive Properties of Biomarkers GDF-15, NTproBNP, and hs-TnT for Morbidity and Mortality in Patients With Type 2 Diabetes With Nephropathy. Diabetes Care. 2017 Jun;40(6):784-792. doi: 10.2337/dc16-2175. Epub 2017 Mar 24.
- 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, MD 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 4 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 28 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: stopped early, as of the sponsor's last update on 19 Mar 2021. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: No difference in protein excretion at 6\&12 months. No safety issues.). Results are not available in the source record.
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?
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). 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 NCT00130312, 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 19 Mar 2021.