Swedish Cardiac And Renal Failure Study-1

NCT ID: NCT07029503

Last Updated: 2025-06-24

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-10-31
• Study Completion Date: 2026-10-31

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.

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single-arm

Eplerenone

Group Type: EXPERIMENTAL

Eplerenone

Intervention Type: 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®).

Interventions

Eplerenone

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®).

Intervention Type: DRUG

Other Intervention Names

Inspra®

Eligibility Criteria

Inclusion Criteria

• 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%
• 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

Exclusion Criteria

• P-K ≥ 5.6
• eGFR < 10 ml/min/1.73m2 according to the revised Lund-Malmö method
• 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
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Karolinska Institutet

OTHER

Sponsor Role: lead

Responsible Party

Carl Haggård

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Krister Lindmark, MD, PhD

Role: STUDY_DIRECTOR

Karolinska Institutet

Locations

Department of Cardiology, Danderyd Hospital, Karolinska Institutet

Stockholm, , Sweden

Countries

Sweden

Central Contacts

Carl Haggård, MD, PhD

Role: CONTACT

carl.haggard@regionstockholm.se

0046735574724

Krister Lindmark, MD, PhD

Role: CONTACT

krister.lindmark@regionstockholm.se

00467028888285

Facility Contacts

Carl Haggård, MD, PhD

Role: primary

carl.haggard@regionstockholm.se

0046735574724

Krister Lindmark, MD, PhD

Role: backup

krister.lindmark@regionstockholm.se

00467028888285

Other Identifiers

2025-520550-11-00

Identifier Type: CTIS

Identifier Source: secondary_id

SCARF-1

Identifier Type: -

Identifier Source: org_study_id