About this trial
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.
Eligibility criteria
Qualifiers
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
Disqualifiers
Inability to understand and sign informed consent
Absolute contra-indication for aldosterone antagonist
Absolute contra-indication for a SGLT2-inhibitor
Heart failure hospitalization, acute coronary syndrome, cardiac surgery, stroke or transient is-chemic attack in the 90 days prior to enrollment
Trial design
Treatments tested in this trial
- vicadrostat / empagliflozin combination 1
- Spironolactone (drug)
Treatment groups
Sponsors and collaborators
University Medical Center Groningen
Lead sponsor
Boehringer Ingelheim
Collaborator
DELPHINIUM
Collaborator