CKDPhase 2COMPARE-VSNCT07304817
Comparative Study on the Mode of Action of Vicadrostat and Spironolactone on Protein Profiles and Renal Hemodynamic Effects (COMPARE-VS)
A Phase 2 study testing vicadrostat / empagliflozin combination 1 and Spironolactone (drug) in people with CKD and Cardiovascular Diseases, run by University Medical Center Groningen at 2 sites in Netherlands.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- CKD, Cardiovascular Diseases, Heart Failure
- What is being tested?
- vicadrostat / empagliflozin combination 1 and Spironolactone (drug)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 2 sitesNetherlands
- Study dates
- 12 May 2026to Feb 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- 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
Show all 15Show fewer
- Serum potassium ≤ 5.0 mmol
- Currently treated or eligible for treatment with Empagliflozin*4
- Not using a MRA or AS inhibitor in the last 6 months prior to enrollment
- On stable doses of other guideline directed medical therapies for ≥ 4 weeks prior to enroll-ment
- 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.
Who cannot join
- 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
- Women who are pregnant, breastfeeding or may be considering pregnancy during the study duration.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands2 sites, 2 recruiting
- Recruiting
Delphinium
Groningen, Provincie Groningen, 9713GZ
Marieke Ettema, +31 (0)6 11277741, m.ettema@delphiniumcro.com
David Smeijers, MD
- Recruiting
University Medical Center Groningen
Groningen, Provincie Groningen, 9713GZ
Kevin Damman, Associate Professor, +31 (0)50 361 11255, k.damman@umcg.nl
Kevin Damman, Associate Professor
About this study
Official title: 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.
Read more
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.
Read the 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.
- Conditions
- CKD, Cardiovascular Diseases, Heart Failure
- Being tested
- vicadrostat / empagliflozin combination 1, Spironolactone (drug)
- Keywords
- COMPARE-VS, Spironolactone, Vicadrostat, CKD, mineralocorticoid receptor antagonist (MRA), aldosterone synthase inhibitor (ASi)
- Medical subject headings
- Cardiovascular Diseases, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
vicadrostat / empagliflozin combination 1Drug
Group 1
Spironolactone (drug)Drug
Group 2
| Study group | Role | What they receive |
|---|---|---|
| Vicadrostat | Experimental | daily treatment with Vicadrostat and background Empagliflozin Receives: Drug: vicadrostat / empagliflozin combination 1 |
| Spironolactone | Active comparator | daily treatment with Spironlactone and background Empagliflozin Receives: Drug: Spironolactone (drug) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Kidney function (eGFR)
Changes in kidney function as determined by change in eGFR
Measured: From baseline to 4 and 26 weeks of treatment.
Secondary outcomes (6)
Renal hemodynamic measurements
Changes in renal hemodynamic measurements
Measured: From baseline to 4 and 26 weeks of treatment
Plasma protein profiles
Plasma protein profiles via proteomics
Measured: From baseline to 4 and 26 weeks of treatment
Urinary protein profiles
Urinary protein profiles via proteomics
Measured: From baseline to 4 and 26 weeks of treatment
Changes in blood concentration markers
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).
Measured: From baseline to 4 and 26 weeks of treatment
Changes in urinary concentration markers
Changes in urinary concentration of sodium, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1)
Measured: From baseline to 4 and 26 weeks of treatment
Changes in UACR
Changes in UACR
Measured: From baseline to 4 and 26 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2025
- Study start12 May 2026
- Primary completionFeb 2028 (estimated)
- Study completionFeb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CKDStudies of the same condition, open and under way.
- More trials run by University Medical Center GroningenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A mechanistic trial using an open-label, parallel-group comparative design with 1:1 randomization and blinded endpoint assessment.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Collaborators
- Boehringer Ingelheim, DELPHINIUM
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07304817
- Sponsor's protocol ID
- COMPARE-VS
- Other IDs
- ECR COMPARE-VS (1378-0052), 2025-523743-35-00, 2025
- Acronym
- COMPARE-VS
- Status last verified
- May 2026
- First submitted
- 20 Nov 2025
- Last updated
- 29 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: will be updated at a later stage
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07304817
- Acronym / sponsor ID
- COMPARE-VS / COMPARE-VS
- Conditions
- CKD, Cardiovascular Diseases, Heart Failure
- Keywords
- COMPARE-VS, Spironolactone, Vicadrostat, CKD, mineralocorticoid receptor antagonist (MRA), aldosterone synthase inhibitor (ASi)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Collaborators
- Boehringer Ingelheim, DELPHINIUM
- Study start
- 12 May 2026 (actual)
- Primary completion
- Feb 2028 (estimated)
- Study completion
- Feb 2028 (estimated)
- First posted
- 26 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- A mechanistic trial using an open-label, parallel-group comparative design with 1:1 randomization and blinded endpoint assessment.
| Arm | Type | Receives |
|---|---|---|
| Vicadrostat | Experimental | Drug: vicadrostat / empagliflozin combination 1daily treatment with Vicadrostat and background Empagliflozin |
| Spironolactone | Active comparator | Drug: Spironolactone (drug)daily treatment with Spironlactone and background Empagliflozin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Provided written and dated informed consent for participation prior to trial admission,
- Age ≥18 years, female or male
- Patients with
- Serum potassium ≤ 5.0 mmol
- Currently treated or eligible for treatment with Empagliflozin*4
Key exclusion criteria (5 listed)
- 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
- Women who are pregnant, breastfeeding or may be considering pregnancy during the study duration.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| vicadrostat / empagliflozin combination 1Group 1 | Drug | Vicadrostat |
| Spironolactone (drug)Group 2 | Drug | Spironolactone |
Primary outcome
Kidney function (eGFR)
Time frame: From baseline to 4 and 26 weeks of treatment.
Changes in kidney function as determined by change in eGFR
6 secondary outcomes
Renal hemodynamic measurements
Time frame: From baseline to 4 and 26 weeks of treatment
Plasma protein profiles
Time frame: From baseline to 4 and 26 weeks of treatment
Urinary protein profiles
Time frame: 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 urinary concentration markers
Time frame: From baseline to 4 and 26 weeks of treatment
Changes in UACR
Time frame: From baseline to 4 and 26 weeks.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2026.
- Individual participant dataSharing planned: Undecided. will be updated at a later stage
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing vicadrostat / empagliflozin combination 1 and Spironolactone (drug) in people with CKD and Cardiovascular Diseases, run by University Medical Center Groningen at 2 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Kidney function (eGFR) (time frame: From baseline to 4 and 26 weeks of treatment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2026.