Comparative Study on the Mode of Action of Vicadrostat and Spironolactone on Protein Profiles and Renal Hemodynamic Effects (COMPARE-VS)

The hypothesis is that renal and cardiac response to a mineralocorticoid receptor antagonist (MRA) differs from the response to an aldosterone synthase inhibitor (ASi) due to the mechanistic differences in action between these two compounds. However, direct head-to-head comparative studies evaluating the renal, cardiac, and systemic effects of MRAs and ASi in patients with chronic kidney disease (CKD), with concomitant cardiovascular disease (CVD) or heart failure (HF), are lacking. The main objective of this study in patients with chronic kidney disease with either cardiovascular disease and/or or heart failure is to compare the effects of the ASi, vicadrostat, with the steroidal MRA, spironolactone, on the change in kidney function from baseline to 4 and 26 weeks. Secondary objectives include * Change in renal hemodynamic measurements from baseline to 4 and 26 weeks * Changes in plasma and urinary protein profiles and associated pathways from baseline to 4 and 26 weeks This is a mechanistic trial using an open-label, parallel-group comparative design with 1:1 randomization and blinded endpoint assessment. Treatment with vicadrostat (Investigational Medicinal Product; IMP 10mg daily) or spironolactone (Comparator IMP; 25-50mg daily) for 26 weeks whilst on empagliflozin (Auxiliary Medicinal Product; AxMP 10mg daily). In half of the enrolled subjects (targeted 50 subjects) renal hemodynamic measurements will be performed at baseline, at 4 and at 26 weeks.