Comparative Study on the Mode of Action of Vicadrostat and Spironolactone on Protein Profiles and Renal Hemodynamic Effects in Patients Chronic Kidney Disease With Cardiovascular Disease /Heart Failure
In this study, investigators will compare the effect of vicadrostat combined with empagliflozin with the effect of spironolactone combined with empagliflozin on renal function and changes in protein profiles in blood and urine. The hypothesis is that the renal and cardiac responses between vicadrostat and spironolactone differ due to mechanistic differences in their mode of action. Spironolactone is a mineralocorticoid receptor antagonist (MRA) and exerts its effect on a receptor, or a type of receiver, found on various cells. Vicadrostat is an aldosterone synthase inhibitor (ASI) and inhibits aldosterone production. Therefore, both drugs affect aldosterone. However, studies evaluating the differences between MRAs (such as spironolactone) and ASI (such as vicadrostat) and examining their effects on the kidneys in patients with chronic kidney disease with concurrent cardiovascular disease, and/or heart failure are still lacking. For this study, all participants will be divided into two groups: * Group 1. Participants in this group will receive one tablet of vicadrostat (10 mg) and one tablet of empagliflozin (10 mg) daily for 26 weeks. * Group 2. Participants in this group will receive one tablet of spironolactone (25 mg) and one tablet of empagliflozin (10 mg) daily for the first four weeks. Participants in this group will then receive two tablets of spironolactone (50 mg) and one tablet of empagliflozin (10 mg) daily for the remaining 22 weeks. The spironolactone dosage may be adjusted during the study period (from 12.5 to 50 mg) based on blood test results.
• Provided written and dated informed consent for participation prior to trial admission,
• Age ≥18 years, female or male
• Patients with
‣ Heart failure\*1 (any LVEF) and eGFR\*2 between 25-90 mL/min/1.73m2 OR
⁃ Established cardiovascular disease\*3 and eGFR between 25-60 mL/min/1.73m2 OR
⁃ Established cardiovascular disease and type 2 diabetes and eGFR between 25-90 mL/min/1.73m2
• Serum potassium ≤ 5.0 mmol
• Currently treated or eligible for treatment with Empagliflozin\*4
• Not using a MRA or AS inhibitor in the last 6 months prior to enrollment
• On stable doses of other guideline directed medical therapies for ≥ 4 weeks prior to enroll-ment
• Outpatient.
‣ 1 HF is defined as the definition used in the most recent ESC guidelines for HF.
⁃ 2 eGFR as assessed by the 2009 CKD-EPI without the race coefficient
⁃ 3 Cardiovascular disease is defined as a history of a myocardial infarction, coronary bypass surgery, PCI, or proven coronary artery disease (e.g. by coronary angiography, CT-scan, etc.)
⁃ 4 If switching from another SGLT2i to Empagliflozin subjects can be enrolled directly. If the subject is not yet on SGLT2i and starts Empagliflozin enrollment can start 4 weeks later see criteria 8.