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

Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity Medical Center Groningen

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

100 Participants
are divided into 2 treatment groups

Sponsors and collaborators

University Medical Center Groningen

Lead sponsor

Boehringer Ingelheim

Collaborator

DELPHINIUM

Collaborator