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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Karolinska Institutet

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Decision date (initial)

2025-08-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Region Stockholm · Swedish research council

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To conduct a pilot trial to evaluate the feasibility and safety of eplerenone in patients with HFrEF and severe CKD. An exploratory analysis of efficacy will also be performed.

Conditions and MedDRA coding

Heart failure with reduced ejection fraction in combination with severe chronic kidney disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. The subject has given their written consent to participate
2. Age ≥ 18
3. A diagnosis of HFrEF according to current criteria since at least three months prior to the screening visit
4. Echocardiography within 24 months of the screening visit with EF ≤ 40%
5. New York Heart Association class II-III
6. Optimally treated and stable HFrEF (according to the investigator) since at least four weeks before the screening visit. Treatment should include BBs, SGLT2Is, ACEIs, or ARBs if eGFR ≥ 20 ml/min/1.73m2 according to the revised Lund-Malmö method. 20 Participants should also have cardiac resynchronization therapy or an implantable cardioverter-defibrillator if the indication exists according to current guidelines
7. eGFR < 30 ml/min/1.73m2 according to the revised Lund-Malmö method at least once during the 12 months prior to the screening visit and eGFR < 45 ml/min/1.73m2 at the time of inclusion

Exclusion criteria 16

1. P-K ≥ 5.5
2. eGFR < 10 ml/min/1.73m2 according to the revised Lund-Malmö method.
3. Ongoing/planned dialysis
4. Systolic blood pressure < 90 mmHg
5. Uncontrolled hypertension as judged by the investigator
6. Severe hepatic impairment (Child-Pugh C)
7. History of, or planned, heart transplantation or left ventricular assist device
8. Unwillingness to comply with highly effective contraceptive methos, or ongoing/planned pregnancy or breastfeeding
9. Previous allergic reaction to a MRA or a potassium binder
10. 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 worth)
11. QTc(f) ≥ 550 msec, history of QT prolongation associated with any medication requiring medication discontinuation, or congenital long QT syndrome
12. Uncontrolled arrythmia as judged by the investigator
13. Acute cardiac hospitalization or procedure within four weeks
14. Acute cardiac hospitalization or procedure within four weeks before inclusion
15. Not suitable as judged by the investigator (presumed inability to participate, severe or terminal co-morbidity and expected survival < 12 months)
16. Previously enrolled in this trial or participation in another trial not approved for co-enrollment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the proportion of subjects who complete the entire treatment period with and without the need to use a potassium binder.

Secondary endpoints 18

1. Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) total symptom score
2. Change in six-minute walk distance (6MWD)
3. Change in N-terminal pro b-type natriuretic peptide (NTpro-BNP)
4. Change in eGFR and urine-albumin-creatinine-ratio (UACR)
5. Safety endpoint: The occurrence of plasma potassium (P-K) ≥ 5.5 and ≥ 6.0
6. Safety endpoint: Hospitalization for hyperkalemia
7. Safety endpoint: The occurrence of P-K < 3.0
8. Safety endpoint: Hospitalization for hypokalemia
9. Safety endpoint: Decrease in eGFR of ≥ 30% and ≥ 50%
10. Safety endpoint: Hospitalization for renal failure
11. Safety endpoint: Initiation of dialysis
12. Safety endpoint: Subject-reported syncope
13. Safety endpoint: Subject-reported lightheadedness due to orthostatic hypotension as judged by the investigator
14. Safety endpoint: Any subject-reported side effect
15. Safety endpoint: Hospitalization for HF
16. Safety endpoint: All cause hospitalization
17. Safety endpoint: Cardiovascular (CV) death
18. Safety endpoint: All cause death

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Karolinska Institutet

Sponsor organisation

Karolinska Institutet

Address

Nobels Vag 6

City

Solna

Postcode

171 65

Country

Sweden

Scientific contact point

Organisation

Karolinska Institutet

Contact name

Krister Lindmark

Public contact point

Organisation

Karolinska Institutet

Contact name

Krister Lindmark

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications