HFrEF - Heart Failure With Reduced Ejection FractionPhase 2SCARF-1NCT07029503
Swedish Cardiac And Renal Failure Study-1
A Phase 2 study testing Eplerenone in people with HFrEF - Heart Failure With Reduced Ejection Fraction and Chronic Kidney Disease, run by Karolinska Institutet at 1 site in Sweden.
Trial summary
Previous studies have shown that patients with heart failure with reduced pumping function and preserved kidney function experience improved symptoms, longer survival, and fewer hospitalizations when treated with medications such as eplerenone. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HFrEF - Heart Failure With Reduced Ejection Fraction, Chronic Kidney Disease
- What is being tested?
- Eplerenone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteSweden
- Study dates
- Feb 2026to Oct 2027
- 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
- The participant has given their written consent to participate
- A diagnosis of HFrEF according to current criteria, for at least three months before the screening visit
- Echocardiography within 24 months of the screening visit with ejection fraction ≤ 40%. The responsible investigator is allowed to order a new TTE at their own discretion if clinically indicated - e.g. following the initiation of markedly intensified HFrEF-treatment or in the event of significant clinical deterioration. If the new TTE shows an EF > 40%, the participant will not be eligible for inclusion. However, a potential echocardiographic worsening should not, by itself, preclude enrollment
- New York Heart Association class II-III
- Optimally treated and stable HFrEF (according to the investigator) since at least four weeks before the screening visit. Treatment should include beta-blockers, sodium/glucose co-transporter 2 inhibitors, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers if eGFR ≥ 20 ml/min/1.73m2 according to the revised Lund-Malmö method. Participants should also have cardiac resynchronization therapy or an implantable cardioverter-defibrillator if the indication exists according to current guidelines
- eGFR < 30 ml/min/1.73m2 according to the revised Lund-Malmö method at least once during the 12 months before the screening visit, and eGFR < 45 ml/min/1.73m2 at the time of inclusion
Who cannot join
- P-K ≥ 5.6
- For the first ten study participants:
- eGFR < 20 ml/min/1.73m2 according to the revised Lund-Malmö method, or projected decline in eGFR to < 10 ml/min/1.73m2 during the 36-week study period. The projected decline will be estimated using the three most recent eGFR values from the previous 6-12 months
- For the remainder of the study participants: eGFR < 10 ml/min/1.73m2 according to the revised Lund-Malmö method, or projected decline in eGFR to < 10 ml/min/1.73m2 during the 36-week study period. The projected decline will be estimated using the three most recent eGFR values from the previous 6-12 months
- Ongoing/planned dialysis
- Systolic blood pressure < 90 mmHg
Show all 17Show fewer
- Uncontrolled hypertension as judged by the investigator
- Severe hepatic impairment (Child-Pugh C)
- History of, or planned, heart transplantation or left ventricular assist device
- Unwillingness to comply with highly effective contraceptive methods, or ongoing/planned pregnancy, or breastfeeding
- Previous allergic reaction to an MRA or a potassium binder
- Ongoing treatment with lithium, cyclosporine, tacrolimus, nonsteroidal anti-inflammatory drugs, trimethoprim, or strong CYP3A inhibitors (ketoconazole, itraconazole, ritonavir, nelfinavir, clarithromycin, telithromycin, and nefazodone) or inducers (rifampicin, carbamazepine, phenytoin, phenobarbital, and St. John's Wort)
- QTc(f) ≥ 550 msec, history of QT prolongation associated with any medication requiring medication discontinuation, or congenital long QT syndrome
- Uncontrolled arrhythmia as judged by the investigator
- Acute cardiac hospitalization or procedure within four weeks before inclusion
- Not suitable as judged by the investigator (presumed inability to participate, severe or terminal co-morbidity, and expected survival < 12 months)
- Previously enrolled in this trial or participation in another trial not approved for co-enrollment
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Sweden1 site, 1 recruiting
- Recruiting
Department of Cardiology, Danderyd Hospital, Karolinska Institutet
Stockholm
Carl Haggård, MD, PhD, 0046735574724, carl.haggard@regionstockholm.se
Krister Lindmark, MD, PhD, 00467028888285, krister.lindmark@regionstockholm.se
About this study
Official title: Swedish Cardiac And Renal Failure Study-1 (SCARF-1): An Open-Label Pilot Trial to Evaluate the Feasibility, Safety and Efficacy of Eplerenone in Patients With Heart Failure With Reduced Ejection Fraction and Severe Chronic Kidney Disease
Previous studies have shown that patients with heart failure with reduced pumping function and preserved kidney function experience improved symptoms, longer survival, and fewer hospitalizations when treated with medications such as eplerenone. However, individuals with impaired kidney function have been excluded from these trials due to concerns about potential adverse effects on potassium levels, kidney function, and possibly also blood pressure. As a result, clear treatment recommendations for this high-risk group are lacking.
In recent years, however, background therapies have been modernized and are now associated with a lower risk of potassium disturbances. Preliminary data also suggest that patients with impaired kidney function may benefit from eplerenone treatment. However, confirmation through dedicated studies is needed.
The primary objective of this pilot trial is to assess the feasibility and safety of eplerenone in patients with heart failure with reduced pumping function and impaired kidney function. Treatment effectiveness will also be explored.
Read the detailed description
Virtually all major trials in heart failure with reduced ejection fraction (HFrEF), including those investigating mineralocorticoid receptor antagonists (MRAs) such as eplerenone, have excluded patients with severe chronic kidney disease (CKD). This exclusion has likely been driven by concerns over the risks of hyperkalemia and worsening renal function (WRF). However, post-hoc analyses of these major trials, along with data from registries and cohort studies, suggest that patients with more advanced renal impairment may still derive an overall benefit from MRA treatment.
The objective of this pilot trial is to evaluate the feasibility and safety of eplerenone in patients with HFrEF and severe CKD. An exploratory analysis of efficacy will also be performed.
- Being tested
- Eplerenone
- Keywords
- HFrEF - Heart Failure with Reduced Ejection Fraction, Chronic kidney disease, Heart failure, Chronic heart failure, HFrEF, CKD, Renal dysfunction, Kidney dysfunction, Renal impairment, Advanced, Severe, Mineralocorticoid receptor antagonists, MRA, Eplerenone, Sodium Zirconium Cyclosilicate, SZC
- Medical subject headings
- Renal Insufficiency, Chronic, Heart Failure, Renal Insufficiency, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EplerenoneDrug
Also called Inspra®
Participants will receive eplerenone 25 mg once daily or every other day, based on baseline potassium levels, eGFR, systolic blood pressure, and concomitant use of weak or moderate CYP3A4 inhibitors.
The study will implement a safety protocol with predefined procedures for managing significant hyperkalemia, worsening renal function, and hypotension. These will include temporary or permanent dose reduction or discontinuation of eplerenone, and, if necessary, administration of the potassium binder sodium zirconium cyclosilicate (SZC, Lokelma®).
| Study group | Role | What they receive |
|---|---|---|
| Single-arm | Experimental | Eplerenone Receives: Drug: Eplerenone |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint is the proportion of participants who complete the treatment period with and without the need to use a potassium binder
Without eplerenone interruption/discontinuation due to safety reasons, with and without SZC
Measured: Between the first and final day of the 12-week eplerenone treatment period
Secondary outcomes (14)
The occurrence of plasma potassium (P-K) ≥ 5.6 and ≥ 6.0
Yes/no
Measured: Between the first and final day of each of the three 12-week study periods
Hospitalization for hyperkalemia
Primary or co-primary reason, yes/no
Measured: Between the first and final day of each of the three 12-week study periods
The occurrence of P-K < 3.0
Yes/no
Measured: Between the first and final day of each of the three 12-week study periods
Hospitalization for hypokalemia
Primary or co-primary reason, yes/no
Measured: Between the first and final day of each of the three 12-week study periods
Decrease in eGFR of ≥ 30% and ≥ 50%
According to the revised Lund-Malmö method in ml/min/1.73 m2, compared to the start of each study period, yes/no
Measured: Between the first and final day of each of the three 12-week study periods
Hospitalization for renal failure
Primary or co-primary reason, yes/no
Measured: Between the first and final day of each of the three 12-week study periods
Initiation of dialysis
Yes/no
Measured: Between the first and final day of each of the three 12-week study periods
Participant-reported lightheadedness due to orthostatic hypotension as judged by the investigator
Yes/no
Measured: Between the first and final day of each of the three 12-week study periods
Participant-reported syncope
Yes/no
Measured: Between the first and final day of each of the three 12-week study periods
Any participant-reported side effect
Yes/No
Measured: Between the first and final day of each of the three 12-week study periods
Hospitalization for heart failure
Primary or co-primary reason, yes/no
Measured: Between the first and final day of each of the three 12-week study periods
All-cause hospitalization
Yes/no
Measured: Between the first and final day of each of the three 12-week study periods
Cardiovascular death
Primary reason, yes/no
Measured: Between the first and final day of each of the three 12-week study periods
All-cause death
Yes/no
Measured: Between the first and final day of each of the three 12-week study periods
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2025
- Study startFeb 2026 (estimated)
- Primary completionFeb 2027 (estimated)
- Study completionOct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HFrEF - Heart Failure With Reduced Ejection FractionStudies of the same condition, open and under way.
- More trials run by Karolinska InstitutetThe 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- ABA-design with a 12-week baseline, a 12-week intervention, and a 12-week withdrawal period. Two observational periods are chosen due to the high risk of natural clinical deterioration, even over a relatively short timeframe, and to enable within-participant comparison of outcome slopes across phases.
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Carl Haggård, Karolinska Institutet
- Investigators
- Krister Lindmark, MD, PhD, Study director, Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07029503
- Sponsor's protocol ID
- SCARF-1
- Other IDs
- 2025-520550-11-00, 2025
- Acronym
- SCARF-1
- Status last verified
- Feb 2026
- First submitted
- 2 Jun 2025
- Last updated
- 24 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data with approved ethical permission. All requests will be evaluated, but this does not mean all requests will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Swedish Cardiac And Renal Failure Study-1 (SCARF-1): An Open-Label Pilot Trial to Evaluate the Feasibility, Safety and Efficacy of Eplerenone in Patients With Heart Failure With Reduced Ejection Fraction and Severe Chronic Kidney Disease
- ClinicalTrials.gov ID
- NCT07029503
- Acronym / sponsor ID
- SCARF-1 / SCARF-1
- Keywords
- HFrEF - Heart Failure with Reduced Ejection Fraction, Chronic kidney disease, Heart failure, Chronic heart failure, HFrEF, CKD, Renal dysfunction, Kidney dysfunction
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Karolinska InstitutetUniversity, hospital or other
- Study start
- Feb 2026 (estimated)
- Primary completion
- Feb 2027 (estimated)
- Study completion
- Oct 2027 (estimated)
- First posted
- 19 Jun 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.
Previous studies have shown that patients with heart failure with reduced pumping function and preserved kidney function experience improved symptoms, longer survival, and fewer hospitalizations when treated with medications such as eplerenone. However, individuals with impaired kidney function have been excluded from these trials due to concerns about potential adverse effects on potassium levels, kidney function, and possibly also blood pressure. As a result, clear treatment recommendations for this high-risk group are lacking.
In recent years, however, background therapies have been modernized and are now associated with a lower risk of potassium disturbances. Preliminary data also suggest that patients with impaired kidney function may benefit from eplerenone treatment. However, confirmation through dedicated studies is needed.
The primary objective of this pilot trial is to assess the feasibility and safety of eplerenone in patients with heart failure with reduced pumping function and impaired kidney function. Treatment effectiveness will also be explored.
Detailed description
Virtually all major trials in heart failure with reduced ejection fraction (HFrEF), including those investigating mineralocorticoid receptor antagonists (MRAs) such as eplerenone, have excluded patients with severe chronic kidney disease (CKD). This exclusion has likely been driven by concerns over the risks of hyperkalemia and worsening renal function (WRF). However, post-hoc analyses of these major trials, along with data from registries and cohort studies, suggest that patients with more advanced renal impairment may still derive an overall benefit from MRA treatment.
The objective of this pilot trial is to evaluate the feasibility and safety of eplerenone in patients with HFrEF and severe CKD. An exploratory analysis of efficacy will also be performed.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- ABA-design with a 12-week baseline, a 12-week intervention, and a 12-week withdrawal period. Two observational periods are chosen due to the high risk of natural clinical deterioration, even over a relatively short timeframe, and to enable within-participant comparison of outcome slopes across phases.
| Arm | Type | Receives |
|---|---|---|
| Single-arm | Experimental | Drug: EplerenoneEplerenone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- The participant has given their written consent to participate
- A diagnosis of HFrEF according to current criteria, for at least three months before the screening visit
- Echocardiography within 24 months of the screening visit with ejection fraction ≤ 40%. The responsible investigator is allowed to order a new TTE at their own discretion if clinically indicated - e.g. following the initiation of markedly intensified HFrEF-treatment or in the event of significant clinical deterioration. If the new TTE shows an EF > 40%, the participant will not be eligible for inclusion. However, a potential echocardiographic worsening should not, by itself, preclude enrollment
- New York Heart Association class II-III
- Optimally treated and stable HFrEF (according to the investigator) since at least four weeks before the screening visit. Treatment should include beta-blockers, sodium/glucose co-transporter 2 inhibitors, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers if eGFR ≥ 20 ml/min/1.73m2 according to the revised Lund-Malmö method. Participants should also have cardiac resynchronization therapy or an implantable cardioverter-defibrillator if the indication exists according to current guidelines
Key exclusion criteria (17 listed)
- P-K ≥ 5.6
- For the first ten study participants:
- eGFR < 20 ml/min/1.73m2 according to the revised Lund-Malmö method, or projected decline in eGFR to < 10 ml/min/1.73m2 during the 36-week study period. The projected decline will be estimated using the three most recent eGFR values from the previous 6-12 months
- For the remainder of the study participants: eGFR < 10 ml/min/1.73m2 according to the revised Lund-Malmö method, or projected decline in eGFR to < 10 ml/min/1.73m2 during the 36-week study period. The projected decline will be estimated using the three most recent eGFR values from the previous 6-12 months
- Ongoing/planned dialysis
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 |
|---|---|---|
| EplerenoneAlso: Inspra®Participants will receive eplerenone 25 mg once daily or every other day, based on baseline potassium levels, eGFR, systolic blood pressure, and concomitant use of weak or moderate CYP3A4 inhibitors. The study will implement a safety protocol with predefined procedures for managing significant hyperkalemia, worsening renal function, and hypotension. These will include temporary or permanent dose reduction or discontinuation of eplerenone, and, if necessary, administration of the potassium binder sodium zirconium cyclosilicate (SZC, Lokelma®). | Drug | Single-arm |
Primary outcome
The primary endpoint is the proportion of participants who complete the treatment period with and without the need to use a potassium binder
Time frame: Between the first and final day of the 12-week eplerenone treatment period
Without eplerenone interruption/discontinuation due to safety reasons, with and without SZC
14 secondary outcomes
The occurrence of plasma potassium (P-K) ≥ 5.6 and ≥ 6.0
Time frame: Between the first and final day of each of the three 12-week study periods
Hospitalization for hyperkalemia
Time frame: Between the first and final day of each of the three 12-week study periods
The occurrence of P-K < 3.0
Time frame: Between the first and final day of each of the three 12-week study periods
Hospitalization for hypokalemia
Time frame: Between the first and final day of each of the three 12-week study periods
Decrease in eGFR of ≥ 30% and ≥ 50%
Time frame: Between the first and final day of each of the three 12-week study periods
Hospitalization for renal failure
Time frame: Between the first and final day of each of the three 12-week study periods
Initiation of dialysis
Time frame: Between the first and final day of each of the three 12-week study periods
Participant-reported lightheadedness due to orthostatic hypotension as judged by the investigator
Time frame: Between the first and final day of each of the three 12-week study periods
Participant-reported syncope
Time frame: Between the first and final day of each of the three 12-week study periods
Any participant-reported side effect
Time frame: Between the first and final day of each of the three 12-week study periods
Hospitalization for heart failure
Time frame: Between the first and final day of each of the three 12-week study periods
All-cause hospitalization
Time frame: Between the first and final day of each of the three 12-week study periods
Cardiovascular death
Time frame: Between the first and final day of each of the three 12-week study periods
All-cause death
Time frame: Between the first and final day of each of the three 12-week study periods
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 24 Feb 2026.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data with approved ethical permission. All requests will be evaluated, but this does not mean all requests will be shared.
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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.
Krister Lindmark, MD, PhD study director
Karolinska Institutet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Eplerenone in people with HFrEF - Heart Failure With Reduced Ejection Fraction and Chronic Kidney Disease, run by Karolinska Institutet at 1 site in Sweden.
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 6 inclusion and 17 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 24 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. 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?
Contact Carl Haggård, MD, PhD (0046735574724, carl.haggard@regionstockholm.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary endpoint is the proportion of participants who complete the treatment period with and without the need to use a potassium binder (time frame: Between the first and final day of the 12-week eplerenone treatment period). 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 24 Feb 2026.