A study to assess the renoprotective effects of the SGLT2 inhibitor Dapagliflozin in non-diabetic patients with proteinuria: a randomized double blind 6-week cross-over trial

Phase 3

Completed

• Conditions: Chronic kidney disease; Kidney function loss; 10029149

• Registration Number: NL-OMON47662
• Lead Sponsor: niversitair Medisch Centrum Groningen

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Last Update Posted: 28 February 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 20

Inclusion Criteria

- Age *18 and *75 years
- Urinary protein excretion > 500 mg/g and * 3500 mg/g in a 24-hr urine collection
- eGFR * 25 mL/min/1.73m2
- On a stable dose of an ACEi or ARB for at least 4 weeks prior to randomization
- Willing to sign informed consent
- Women of Child-Bearing Potential (WOCBP) must be using an acceptable method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of study drug in such a manner that the risk of pregnancy is minimized.
- WOCBP must have a negative serum or urine pregnancy test result (minimum sensitivity 25 IU/L or equivalent units of HCG) within 0 to 72 hours before the first dose of study drug.
- Women must not be breast-feeding

Exclusion Criteria

- Diagnosis of type 1 or type 2 diabetes mellitus
- Urinary protein excretion > 3500 mg/day
- Peripheral Vascular Disease
- Autosomal dominant polycystic kidney disease or autosomal recessive polycystic kidney disease, lupus nephritis, or ANCA-associated vasculitis
- Indication for immunosuppressants as per the treating physician*s judgment.
- Receiving cytotoxic therapy, immunosuppressive therapy, or other immunotherapy for primary or secondary renal disease within 6 months prior to enrolment.
- Active malignancy aside from treated squamous cell or basal cell carcinoma of the skin.
- Any medication, surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of medications including, but not limited to any of the following:
o History of active inflammatory bowel disease within the last six months;
o Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;
o Gastro-intestinal ulcers and/or gastrointestinal or rectal bleeding within last six months;
o Pancreatic injury or pancreatitis within the last six months;
o Evidence of hepatic disease as determined by any one of the following: ALT or AST values exceeding 3x ULN at the screening visit, a history of hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt;
o Evidence of urinary obstruction of difficulty in voiding at screening
- History of severe hypersensitivity or contraindications to dapagliflozin
- History of hypersensitivity or contraindications to iodinated contrast media
- Subject who may be at risk for dehydration or volume depletion that may affect the interpretation of efficacy or safety data
- Participation in any clinical investigation within 3 months prior to initial dosing.
- Donation or loss of 400 ml or more of blood within 8 weeks prior to initial dosing.
- History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during the screening.
- History of noncompliance to medical regimens or unwillingness to comply with the study protocol.
- Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study.
- Pregnancy or breastfeeding
- WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and up to 4 weeks after the last dose of study drug.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Main study parameters/endpoints: Change in 24-hr proteinuria</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary study parameters/endpoints (if applicable)<br /><br>* Glomerular Filtration Rate measured with iohexol<br /><br>* Systolic/diastolic blood pressure<br /><br>* Neurohormones/biomarkers<br /><br>o Hormones of the RAAS (renin, aldosterone in plasma and urine)<br /><br>o Natriuretic Peptides<br /><br>o Urinary adenosine<br /><br>o Co-peptin<br /><br>o Immunoglobulin G<br /><br><br /><br>Other study parameters (if applicable)<br /><br>* Number of hypoglycaemic episodes<br /><br>* Serious Adverse Events<br /><br>* Drug related adverse events (causality to investigational product assessed by<br /><br>research physician).</p><br>