Effects of Dapagliflozin on EChOcardiographic Measures of CarDiac StructurE and Function in Patients with CKD

Prior treatment

• Treatment with SGLT2 inhibitor within 8 weeks prior to enrolment
• Coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting) or valvular repair/replacement within 12 weeks prior to enrolment
• Participation in another clinical study with an investigational product within the last month prior to enrolment
• Inability to understand or comply with the investigational product, procedures, and/or follow-up or any conditions that may prevent the participant to complete the study

Other illness

• Type 1 diabetes
• For patients with type 2 diabetes:
  • History of diabetic ketoacidosis
• History of organ transplant
• Known allergy or hypersensitivity to SGLT2 inhibitors or Placebo ingredients
• Myocardial infarction, unstable angina, stroke or transient ischemic attack within 12 weeks of enrolment
• Known blood-borne diseases, such as Hepatitis A, B, C, D, and E, and Human immunodeficiency virus (HIV) types 1 and 2, Ebola, Lassa fever virus.

Lab values

• Hepatic impairment (aspartate transaminase or alanine transaminase \>3 times the upper limit of normal \[ULN\] or total bilirubin \>2 times the ULN at the time of enrolment)

Age

• Any condition outside the renal and cardiovascular study area with a life expectancy of \<2 years based on investigator's clinical judgement

Other

• Patients undergoing dialysis
• Female patients who are pregnant, lactating, or are considering becoming pregnant during the study or for 6 months after study completion

• Signed informed consent
• ≥ 18 years of age
• Chronic kidney disease (CKD), defined as evidence of decreased eGFR (eGFR ≥20 and \<60 mL/minute per 1.73 m2) or between eGFR ≥60 and \<90 mL/minute per 1.73 m2 with urinary albumin:creatinine ratio ≥200 mg/g or protein:creatinine ratio ≥300 mg/g
• Stable treatment with clinically appropriate doses of ACEi/ARB among CKD patients with proteinuria and uptitrated to maximal recommended or tolerated dose for at least 4 weeks before randomization, if not medically contraindicated
• For patients with type 2 diabetes:
  • Stable antihyperglycemic treatment \> 30 days before screening
• Female patients should either not be of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile, or is of childbearing potential and practicing one of the following methods of contraception throughout the study and for 30 days after study completion: Hormonal contraception (oral contraceptives, contraceptive implant, injectable birth control, contraceptive patch, or vaginal ring) or intrauterine device
• Ability to understand and read Danish