Swedish Cardiac And Renal Failure Study-1

NCT07029503 | Recruiting Phase 2

• 2 other identifiers: SCARF-12025-520550-11-00
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

HFrEF - Heart Failure With Reduced Ejection Fraction; Chronic Kidney Disease

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

Outcome Measures

Primary Outcomes (1)

• 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

  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

  Between the first and final day of each of the three 12-week study periods

• Hospitalization for hyperkalemia

  Between the first and final day of each of the three 12-week study periods

• The occurrence of P-K < 3.0

  Between the first and final day of each of the three 12-week study periods

• Hospitalization for hypokalemia

  Between the first and final day of each of the three 12-week study periods

• Decrease in eGFR of ≥ 30% and ≥ 50%

  Between the first and final day of each of the three 12-week study periods

Other Outcomes (34)

• Kansas City Cardiomyopathy Questionnaire (KCCQ) total symptom score

  At the end of the 12-week eplerenone treatment period, compared with the scores at the end of the 12-week baseline period and the end of the 12-week withdrawal period

• Six-Minute Walk Test (6MWD)

  At the end of the 12-week eplerenone treatment period, compared with the values at the end of the 12-week baseline period and the end of the 12-week withdrawal period

• N-terminal pro b-type natriuretic peptide (NTpro-BNP)

  At the end of the 12-week eplerenone treatment period, compared with the values at the end of the 12-week baseline period and the end of the 12-week withdrawal period

Study Arms (1)

Single-arm

EXPERIMENTAL

Eplerenone

Drug: Eplerenone

Interventions

Eplerenone DRUG

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®).

Also known as: Inspra®

Single-arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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
• Not suitable as judged by the investigator (presumed inability to participate, severe or terminal co-morbidity, and expected survival \< 12 months)

Sponsors & Collaborators

• Karolinska Institutet: lead

Study Sites (1)

Department of Cardiology, Danderyd Hospital, Karolinska Institutet

Stockholm, Sweden

RECRUITING

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Heart Failure; Renal Insufficiency; Lymphoma, Follicular

Interventions

Eplerenone

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Heart Diseases; Cardiovascular Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Krister Lindmark, MD, PhD

  Karolinska Institutet

  STUDY DIRECTOR

Central Study Contacts

Carl Haggård, MD, PhD

CONTACT

0046735574724; carl.haggard@regionstockholm.se

Krister Lindmark, MD, PhD

CONTACT

00467028888285; krister.lindmark@regionstockholm.se

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Transthoracic Echocardiography (TTE) analysis will take place retrospectively in a blinded manner
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Model Details: 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.

Study Record Dates

• First Submitted: June 2, 2025
• First Posted: June 19, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: The IPD and supporting information will be shared after publication of the results in a peer-reviewed medical journal, and will be available for a minimum of 25 years therafter.
• Access Criteria: Access to IPD and supporting information may be granted to qualified researchers whose intended use is to evaluate the trial, provided that participant anonymity is maintained.

Locations

SE (1)