Trial Outcomes & Findings for Effect of Sulodexide in Early Diabetic Nephropathy (NCT NCT00130208)

Last Updated: 2018-03-23

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1056 participants

Primary outcome timeframe

26 Weeks

Results posted on

2018-03-23

Participant Flow

Participant milestones

Participant milestones
Measure	Sulodexide Also known as KRX-101. All patients will be on standard of care ACE or ARBs. Sulodexide: 100 mg sulodexide gelcaps	Placebo All patients will be on standard of care ACE or ARBs. Placebo: 0 mg gelcap
Maintenance Period (26 Weeks) STARTED	524	532
Maintenance Period (26 Weeks) Valid Albumin Creatinine Ratio	492	494
Maintenance Period (26 Weeks) COMPLETED	500	502
Maintenance Period (26 Weeks) NOT COMPLETED	24	30
Washout Period (8 Weeks) STARTED	500	502
Washout Period (8 Weeks) COMPLETED	494	490
Washout Period (8 Weeks) NOT COMPLETED	6	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Sulodexide Also known as KRX-101. All patients will be on standard of care ACE or ARBs. Sulodexide: 100 mg sulodexide gelcaps	Placebo All patients will be on standard of care ACE or ARBs. Placebo: 0 mg gelcap
Maintenance Period (26 Weeks) Adverse Event	10	12
Maintenance Period (26 Weeks) Physician Decision	0	2
Maintenance Period (26 Weeks) Withdrawal by Subject	8	11
Maintenance Period (26 Weeks) Lost to Follow-up	5	4
Maintenance Period (26 Weeks) Other	1	1
Washout Period (8 Weeks) Adverse Event	3	6
Washout Period (8 Weeks) Withdrawal by Subject	2	4
Washout Period (8 Weeks) Lost to Follow-up	0	1
Washout Period (8 Weeks) Other	1	1

Baseline Characteristics

Effect of Sulodexide in Early Diabetic Nephropathy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sulodexide n=524 Participants Also known as KRX-101. All patients will be on standard of care ACE or ARBs. Sulodexide: 100 mg sulodexide gelcaps	Placebo n=532 Participants All patients will be on standard of care ACE or ARBs. Placebo: 0 mg gelcap	Total n=1056 Participants Total of all reporting groups
Age, Continuous	62.0 years STANDARD_DEVIATION 9.73 • n=113 Participants	62.3 years STANDARD_DEVIATION 9.90 • n=163 Participants	62.2 years STANDARD_DEVIATION 9.82 • n=160 Participants
Sex: Female, Male Female	130 Participants n=113 Participants	124 Participants n=163 Participants	254 Participants n=160 Participants
Sex: Female, Male Male	394 Participants n=113 Participants	408 Participants n=163 Participants	802 Participants n=160 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	28 Participants n=113 Participants	31 Participants n=163 Participants	59 Participants n=160 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	496 Participants n=113 Participants	501 Participants n=163 Participants	997 Participants n=160 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=113 Participants	0 Participants n=163 Participants	0 Participants n=160 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=113 Participants	2 Participants n=163 Participants	4 Participants n=160 Participants
Race (NIH/OMB) Asian	33 Participants n=113 Participants	34 Participants n=163 Participants	67 Participants n=160 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=113 Participants	2 Participants n=163 Participants	3 Participants n=160 Participants
Race (NIH/OMB) Black or African American	39 Participants n=113 Participants	28 Participants n=163 Participants	67 Participants n=160 Participants
Race (NIH/OMB) White	440 Participants n=113 Participants	451 Participants n=163 Participants	891 Participants n=160 Participants
Race (NIH/OMB) More than one race	8 Participants n=113 Participants	15 Participants n=163 Participants	23 Participants n=160 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=113 Participants	0 Participants n=163 Participants	1 Participants n=160 Participants

PRIMARY outcome

Timeframe: 26 Weeks

Outcome measures

Outcome measures
Measure	Sulodexide n=492 Participants Also known as KRX-101. All patients will be on standard of care ACE or ARBs. Sulodexide: 100 mg sulodexide gelcaps	Placebo n=494 Participants All patients will be on standard of care ACE or ARBs. Placebo: 0 mg gelcap
Number of Subjects With Conversion From Microalbuminuria to Normoalbuminuria	39 Participants	30 Participants

PRIMARY outcome

Timeframe: 26 Weeks

During the treatment period, KRX-101 is being compared to placebo to assess whether a 50% reduction in microalbuminuria has been achieved.

Outcome measures

Outcome measures
Measure	Sulodexide n=492 Participants Also known as KRX-101. All patients will be on standard of care ACE or ARBs. Sulodexide: 100 mg sulodexide gelcaps	Placebo n=494 Participants All patients will be on standard of care ACE or ARBs. Placebo: 0 mg gelcap
Number of Subjects With Greater Than 50% Reduction in Microalbuminuria	76 Participants	87 Participants

SECONDARY outcome

Timeframe: 26 Weeks

Population: Participant numbers include those with both baseline and week 26 measurements

Outcome measures

Outcome measures
Measure	Sulodexide n=489 Participants Also known as KRX-101. All patients will be on standard of care ACE or ARBs. Sulodexide: 100 mg sulodexide gelcaps	Placebo n=496 Participants All patients will be on standard of care ACE or ARBs. Placebo: 0 mg gelcap
Change in Serum Albumin From Baseline to End of 26 Weeks	-0.02 percent change Standard Error 0.01	-0.02 percent change Standard Error 0.01

Adverse Events

Sulodexide

Serious events: 21 serious events

Other events: 348 other events

Deaths: 2 deaths

Placebo

Serious events: 33 serious events

Other events: 358 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Information

Keryx Biopharmaceuticals

Phone: 1-844-44-KERYX

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Sulodexide n=523 participants at risk Also known as KRX-101. All patients will be on standard of care ACE or ARBs. Sulodexide: 100 mg sulodexide gelcaps	Placebo n=532 participants at risk All patients will be on standard of care ACE or ARBs. Placebo: 0 mg gelcap
Cardiac disorders Atrioventricular block complete	0.19% 1/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.00% 0/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Blood and lymphatic system disorders Post-procedural hematoma	0.19% 1/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.00% 0/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.19% 1/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.00% 0/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Hepatobiliary disorders Cholecystitis	0.19% 1/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.00% 0/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Cardiac disorders Ischaemic Cardiomyopathy	0.19% 1/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.00% 0/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Infections and infestations Subcutaneous Abscess	0.19% 1/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.00% 0/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Respiratory, thoracic and mediastinal disorders Pulmonary edema	0.19% 1/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.00% 0/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Cardiac disorders Supraventricular Tachycardia	0.19% 1/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.00% 0/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Cardiac disorders Myocardial Infarction	0.19% 1/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.00% 0/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Renal and urinary disorders Renal Failure Acute	0.19% 1/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.19% 1/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Cardiac disorders Acute Coronary Syndrome	0.19% 1/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.19% 1/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Cardiac disorders Aortic Stenosis	0.19% 1/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.00% 0/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Cardiac disorders Aortic Aneurysm	0.19% 1/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.00% 0/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Cardiac disorders Transient ischemic attack	0.19% 1/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.00% 0/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Metabolism and nutrition disorders Diabetic Foot	0.19% 1/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.00% 0/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Infections and infestations Pancreatitis	0.19% 1/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.00% 0/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Injury, poisoning and procedural complications Device Failure	0.19% 1/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.00% 0/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Gastrointestinal disorders Intestinal Obstruction	0.19% 1/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.00% 0/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Infections and infestations Cellulitis	0.00% 0/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.19% 1/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Musculoskeletal and connective tissue disorders Scoliosis	0.00% 0/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.19% 1/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
General disorders Death	0.00% 0/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.38% 2/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Nervous system disorders Cerebrovascular Accident	0.19% 1/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.56% 3/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Cardiac disorders Coronary artery disease	0.00% 0/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.19% 1/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Respiratory, thoracic and mediastinal disorders Lung Disorder	0.00% 0/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.19% 1/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Infections and infestations Sigmoiditis	0.19% 1/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.00% 0/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.19% 1/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.00% 0/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Musculoskeletal and connective tissue disorders Spinal Cord Stenosis	0.00% 0/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.19% 1/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Respiratory, thoracic and mediastinal disorders Acute Respiratory Distress	0.00% 0/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.19% 1/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Infections and infestations Septic Shock	0.00% 0/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.19% 1/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Infections and infestations Osteomyelitis	0.00% 0/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.19% 1/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian Cancer	0.00% 0/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.19% 1/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Cardiac disorders Carotid Artery Stenosis	0.00% 0/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.19% 1/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon Cancer Metastatic	0.00% 0/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.19% 1/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Cardiac disorders Cardiac Failure	0.00% 0/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.38% 2/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	0.00% 0/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.19% 1/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-Hodgkins Lymphoma	0.00% 0/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.19% 1/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal Cancer	0.00% 0/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.19% 1/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Respiratory, thoracic and mediastinal disorders Obstructive Airways Disorder	0.00% 0/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.19% 1/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Cardiac disorders Atrial Fibrillation	0.00% 0/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.19% 1/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Cardiac disorders Cardiomyopathy	0.00% 0/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.19% 1/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication

Other adverse events
Measure	Sulodexide n=523 participants at risk Also known as KRX-101. All patients will be on standard of care ACE or ARBs. Sulodexide: 100 mg sulodexide gelcaps	Placebo n=532 participants at risk All patients will be on standard of care ACE or ARBs. Placebo: 0 mg gelcap
Cardiac disorders Coronary Artery Disease	1.1% 6/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.56% 3/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Gastrointestinal disorders Diarrhea	4.0% 21/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	3.8% 20/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Gastrointestinal disorders Constipation	1.9% 10/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	2.1% 11/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Gastrointestinal disorders Nausea	1.9% 10/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	1.1% 6/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Gastrointestinal disorders Abdominal Pain	0.76% 4/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	1.1% 6/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Gastrointestinal disorders Dyspepsia	0.57% 3/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	1.1% 6/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
General disorders Edema Peripheral	10.5% 55/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	12.2% 65/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
General disorders Edema	2.5% 13/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	2.3% 12/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
General disorders Chest Pain	1.5% 8/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	1.1% 6/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
General disorders Asthenia	1.7% 9/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.75% 4/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
General disorders Fatigue	0.76% 4/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	1.7% 9/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Respiratory, thoracic and mediastinal disorders Upper Respiratory Tract Infection	3.4% 18/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	4.5% 24/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Respiratory, thoracic and mediastinal disorders Nasopharyngitis	4.0% 21/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	3.4% 18/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Infections and infestations Urinary Tract Infection	3.1% 16/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	3.8% 20/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Infections and infestations Bronchitis	1.7% 9/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	3.0% 16/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Infections and infestations Influenza	1.5% 8/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	2.3% 12/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Infections and infestations Sinusitis	1.7% 9/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.94% 5/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Infections and infestations Gastroenteritis	0.57% 3/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	1.1% 6/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Investigations Cardiac Murmur	0.96% 5/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	1.7% 9/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Investigations Weight Increased	1.1% 6/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.75% 4/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Investigations Blood glucose increased	0.19% 1/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	1.1% 6/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Metabolism and nutrition disorders Hypoglycaemia	1.9% 10/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	1.5% 8/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Metabolism and nutrition disorders Hyperglycaemia	1.1% 6/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	1.5% 8/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Metabolism and nutrition disorders Hyperkalaemia	1.7% 9/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.94% 5/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Musculoskeletal and connective tissue disorders Back Pain	2.5% 13/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	3.2% 17/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Musculoskeletal and connective tissue disorders Pain in extremities	2.1% 11/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	3.6% 19/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Musculoskeletal and connective tissue disorders Arthralgia	2.5% 13/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	2.4% 13/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Musculoskeletal and connective tissue disorders Muscle Spasms	1.3% 7/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	1.7% 9/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Nervous system disorders Headache	3.1% 16/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	3.2% 17/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Nervous system disorders Dizziness	2.5% 13/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	2.8% 15/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Nervous system disorders Hypoesthesia	0.38% 2/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	1.1% 6/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Psychiatric disorders Depression	0.38% 2/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	1.5% 8/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Respiratory, thoracic and mediastinal disorders Cough	2.7% 14/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	1.7% 9/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Respiratory, thoracic and mediastinal disorders Rales	1.3% 7/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	2.1% 11/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.1% 6/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	1.5% 8/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Respiratory, thoracic and mediastinal disorders Epistaxis	1.1% 6/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.38% 2/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Skin and subcutaneous tissue disorders Rash	1.3% 7/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	1.7% 9/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Vascular disorders Hypertension	2.3% 12/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	2.8% 15/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication
Vascular disorders Hypotension	1.3% 7/523 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication	0.94% 5/532 • Adverse event data was collected for the full duration of the trial (34 weeks) The safety population consisted of all patients who were administered at least 1 dose of study medication. There was one patient in the sulodexide group who was randomized but did not receive study medication