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

May 28, 2026 updated by: University Medical Center Groningen

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • Provincie Groningen
      • Groningen, Provincie Groningen, Netherlands, 9713GZ
        • Recruiting
        • University Medical Center Groningen
        • Contact:
          • Kevin Damman, Associate Professor
          • Phone Number: +31 (0)50 361 11255
          • Email: k.damman@umcg.nl
        • Principal Investigator:
          • Kevin Damman, Associate Professor
      • Groningen, Provincie Groningen, Netherlands, 9713GZ
        • Recruiting
        • Delphinium
        • Contact:
        • Principal Investigator:
          • David Smeijers, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Vicadrostat
daily treatment with Vicadrostat and background Empagliflozin
Drug: vicadrostat / empagliflozin combination 1
Group 1
Active Comparator: Spironolactone
daily treatment with Spironlactone and background Empagliflozin
Drug: Spironolactone (drug)
Group 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Kidney function (eGFR)
Time Frame: From baseline to 4 and 26 weeks of treatment.
Changes in kidney function as determined by change in eGFR
From baseline to 4 and 26 weeks of treatment.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Renal hemodynamic measurements
Time Frame: From baseline to 4 and 26 weeks of treatment
Changes in renal hemodynamic measurements
From baseline to 4 and 26 weeks of treatment
Plasma protein profiles
Time Frame: From baseline to 4 and 26 weeks of treatment
Plasma protein profiles via proteomics
From baseline to 4 and 26 weeks of treatment
Urinary protein profiles
Time Frame: From baseline to 4 and 26 weeks of treatment
Urinary protein profiles via proteomics
From baseline to 4 and 26 weeks of treatment
Changes in blood concentration markers
Time Frame: From baseline to 4 and 26 weeks of treatment
Changes in blood (serum and plasma) concentrations of potassium, creatinine, neutrophil gelatinase-associated lipocalin (NGAL), renin, angiotensin II, aldosterone, and kidney injury molecule-1 (KIM-1).
From baseline to 4 and 26 weeks of treatment
Changes in urinary concentration markers
Time Frame: From baseline to 4 and 26 weeks of treatment
Changes in urinary concentration of sodium, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1)
From baseline to 4 and 26 weeks of treatment
Changes in UACR
Time Frame: From baseline to 4 and 26 weeks.
Changes in UACR
From baseline to 4 and 26 weeks.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Medical Center Groningen

Collaborators

Boehringer Ingelheim
DELPHINIUM

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 12, 2026

Primary Completion (Estimated)

February 1, 2028

Study Completion (Estimated)

February 1, 2028

Study Registration Dates

First Submitted

November 20, 2025

First Submitted That Met QC Criteria

December 12, 2025

First Posted (Actual)

December 26, 2025

Study Record Updates

Last Update Posted (Actual)

May 29, 2026

Last Update Submitted That Met QC Criteria

May 28, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • COMPARE-VS
  • ECR COMPARE-VS (1378-0052) (Other Grant/Funding Number: Boehringer Ingelheim International GmbH)
  • 2025-523743-35-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

will be updated at a later stage

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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