Spironolactone Alternate Dosing vs Finerenone in Elevated Potassium - K Safety Study

Official title

Safety of Finerenone Versus Alternate-Day Spironolactone in Patients With Heart Failure and Diabetic Kidney Disease at High Risk for Hyperkalemia: The SAFE-K Randomized Trial

Overview

This study evaluates the safety of finerenone compared with alternate-day spironolactone in patients with heart failure and diabetic kidney disease at increased risk of hyperkalemia. Patients with chronic kidney disease and heart failure often benefit from mineralocorticoid receptor antagonists, but their use is frequently limited by elevated potassium levels. Finerenone has been associated with a lower risk of hyperkalemia in clinical trials, but direct comparisons with spironolactone in high-risk patients are limited. In this randomized study, eligible participants will be assigned to receive either finerenone once daily or spironolactone on alternate days, in addition to standard therapy. Patients will be closely monitored during hospitalization and followed for 4 weeks. The primary outcome is clinically relevant hyperkalemia, defined by elevated potassium levels or the need to adjust or discontinue treatment due to hyperkalemia. Secondary outcomes include changes in potassium levels, kidney function, and clinical events. This study aims to provide practical evidence to guide the safe use of mineralocorticoid receptor antagonists in patients at high risk for hyperkalemia.

Detailed description

This is a prospective, randomized, open-label, blinded endpoint (PROBE), single-center study designed to compare the safety of finerenone versus alternate-day spironolactone in patients with heart failure and diabetic kidney disease at increased risk of hyperkalemia.

Mineralocorticoid receptor antagonists (MRAs) are a cornerstone therapy in patients with heart failure and have demonstrated benefits in patients with diabetic kidney disease. However, their use is often limited by hyperkalemia, particularly in patients with impaired renal function and elevated baseline potassium levels. Finerenone, a non-steroidal MRA, has shown a more favorable safety profile compared to steroidal MRAs in previous trials, but direct head-to-head comparisons in high-risk populations are lacking.

Eligible participants will be adults with heart failure and diabetic kidney disease with elevated baseline potassium levels. After providing informed consent, participants will be randomized in a 1:1 ratio to receive either finerenone once daily or spironolactone administered on alternate days, in addition to standard of care therapy.

Participants will undergo intensive monitoring during hospitalization, including daily assessment of serum potassium and renal function for up to 7 days or until discharge. After hospital discharge, participants will be followed in the outpatient setting for a total of 4 weeks, with scheduled visits and laboratory monitoring.

The primary endpoint is the incidence of clinically relevant hyperkalemia within 4 weeks, defined as serum potassium ≥ 5.5 mEq/L, treatment interruption or dose adjustment due to hyperkalemia, or the need for potassium-lowering therapy.

Secondary endpoints include change in serum potassium levels, time to first hyperkalemia event, incidence of severe hyperkalemia (≥ 6.0 mEq/L), treatment discontinuation, changes in renal function, and exploratory clinical outcomes such as heart failure hospitalization, arrhythmias, and all-cause mortality.

This study aims to provide pragmatic, clinically applicable evidence to inform the use of MRAs in a high-risk cardiorenal population.

Interventions

• Drug Finerenone
  Finerenone 10 mg administered orally once daily. Treatment is given in addition to standard of care therapy for heart failure and diabetic kidney disease. Dose interruption or discontinuation may occur according to protocol-defined safety criteria, particularly in the setting of hyperkalemia.
• Drug Spironolactone (drug)
  Spironolactone 25 mg administered orally on alternate days. Treatment is given in addition to standard of care therapy for heart failure and diabetic kidney disease. Dose interruption or discontinuation may occur according to protocol-defined safety criteria, particularly in the setting of hyperkalemia.

Primary outcome measures

• Clinically Relevant Hyperkalemia [Time frame: Up to 4 weeks after randomization]

Secondary outcome measures (4)

• Change in Serum Potassium [Time frame: Baseline to 4 weeks]
• Time to First Hyperkalemia Event [Time frame: Up to 4 weeks]
• Temporary or Permanent Discontinuation of Study Drug [Time frame: Up to 4 weeks]
• Change in Albuminuria and in Renal Function [Time frame: Up to 4 weeks.]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years
• Diagnosis of heart failure, regardless of left ventricular ejection fraction
• Diagnosis of type 2 diabetes mellitus
• Diabetic kidney disease, defined by the presence of albuminuria (urinary albumin-to-creatinine ratio ≥ 30 mg/g)
• Estimated glomerular filtration rate (eGFR) ≥ 25 mL/min/1.73 m²
• Serum potassium between 5.0 and 5.5 mEq/L at screening
• Receiving or eligible to receive standard of care therapy for heart failure
• Ability to provide written informed consent
• Ability to comply with study procedures and follow-up visits

Exclusion criteria

• Serum potassium > 5.5 mEq/L at screening
• Acute kidney injury at the time of enrollment
• Symptomatic hypotension or systolic blood pressure < 90 mmHg
• Clinically significant arrhythmias requiring immediate intervention
• Known hypersensitivity or contraindication to finerenone or spironolactone
• Use of potassium-sparing diuretics other than the study drugs
• Pregnancy or breastfeeding
• Participation in another interventional clinical trial
• Any condition that, in the opinion of the investigator, would make participation unsafe or interfere with study procedures

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07523867 · HM-IC-SAFEK

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗