Chronic kidney disease Kidney function loss
Conditions
Interventions
Dapagliflozin 10 mg/day, once a day in the morning OR matched placebo once a
day in the morning.
Chronic
Dapagliflozin
Diabetes Mellitus
Renal insufficiency
Sodium-glucose transporter 2
Sponsors
Universitair Medisch Centrum Groningen
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
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
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main study parameters/endpoints: Change in 24-hr proteinuria | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary study parameters/endpoints (if applicable) * Glomerular Filtration Rate measured with iohexol * Systolic/diastolic blood pressure * Neurohormones/biomarkers o Hormones of the RAAS (renin, aldosterone in plasma and urine) o Natriuretic Peptides o Urinary adenosine o Co-peptin o Immunoglobulin G Other study parameters (if applicable) * Number of hypoglycaemic episodes * Serious Adverse Events * Drug related adverse events (causality to investigational product assessed by research physician). | — |
Countries
The Netherlands
Outcome results
None listed