Vicadrostat versus spironolactone: effects on kidney function and protein markers

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

Phase 2 Interventional University Medical Center Groningen · NCT07304817

This will test whether vicadrostat or spironolactone, each given with empagliflozin, changes kidney function and blood/urine protein patterns in adults with CKD and heart disease or heart failure.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment100 (estimated)
Ages18 Years and up
SexAll
SponsorUniversity Medical Center Groningen Academic / other
Locations2 sites (Groningen, Provincie Groningen and 1 other locations)
Trial IDNCT07304817 on ClinicalTrials.gov

What this trial studies

This is a phase 2, open-label, parallel-group trial with 1:1 randomization and blinded endpoint assessment comparing vicadrostat (10 mg daily) to spironolactone (25–50 mg daily) on a background of empagliflozin (10 mg daily) for 26 weeks. The primary focus is change in kidney function from baseline to 4 and 26 weeks, with secondary measures including renal hemodynamics and plasma/urinary proteomic profiles. Approximately half of participants (target ~50) will undergo detailed renal hemodynamic testing at baseline, 4 and 26 weeks. The trial enrolls adults with CKD who also have heart failure or established cardiovascular disease to explore mechanistic differences between an aldosterone synthase inhibitor and a mineralocorticoid receptor antagonist.

Who should consider this trial

Good fit: Adults (≥18) with chronic kidney disease and either heart failure (any LVEF) or established cardiovascular disease, with eGFR in the protocol-specified ranges (25–90 or 25–60 mL/min/1.73 m2 depending on subgroup), serum potassium ≤5.0 mmol/L, eligible for empagliflozin, not on an MRA or ASI in the prior 6 months, and stable on other guideline therapies are eligible.

Not a fit: People with eGFR outside the allowed ranges, serum potassium >5.0 mmol/L, recent use of MRAs/ASIs, or who are unable or ineligible to take empagliflozin are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the trial could identify whether vicadrostat provides equal or better kidney protection than spironolactone and help guide safer, more targeted aldosterone-directed therapy for people with CKD and cardiovascular disease.

How similar studies have performed: Steroidal MRAs like spironolactone have evidence for benefit in heart failure but carry hyperkalemia risk, while ASIs such as vicadrostat are a newer approach with limited clinical outcome data and no prior direct head-to-head renal comparisons.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

1. Provided written and dated informed consent for participation prior to trial admission,
2. Age ≥18 years, female or male
3. 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
4. Serum potassium ≤ 5.0 mmol
5. Currently treated or eligible for treatment with Empagliflozin\*4
6. Not using a MRA or AS inhibitor in the last 6 months prior to enrollment
7. On stable doses of other guideline directed medical therapies for ≥ 4 weeks prior to enroll-ment
8. 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.

Exclusion Criteria:

1. Inability to understand and sign informed consent
2. Absolute contra-indication for aldosterone antagonist
3. Absolute contra-indication for a SGLT2-inhibitor
4. Heart failure hospitalization, acute coronary syndrome, cardiac surgery, stroke or transient is-chemic attack in the 90 days prior to enrollment
5. Women who are pregnant, breastfeeding or may be considering pregnancy during the study duration.

Where this trial is running

Groningen, Provincie Groningen and 1 other locations

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions CKDCardiovascular DiseasesHeart FailureCOMPARE-VSSpironolactoneVicadrostatmineralocorticoid receptor antagonistaldosterone synthase inhibitor
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.