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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Failure; Diabetic Kidney Disease; Hyperkalemia
• Intervention / Treatment: Drug: Finerenone; Drug: Spironolactone (drug)

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jefferson L Vieira, MD, PHD; Phone Number: +5585981236289; Email: unidadepesquisaclinica@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Finerenone; Participants assigned to this arm will receive finerenone 10 mg orally once daily, in addition to standard of care therapy for heart failure and diabetic kidney disease.	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.
Active Comparator: Alternate-Day Spironolactone; Participants assigned to this arm will receive spironolactone 25 mg orally on alternate days, in addition to standard of care therapy for heart failure and diabetic kidney disease.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinically Relevant Hyperkalemia	Clinically relevant hyperkalemia is defined as the occurrence of any of the following: serum potassium ≥ 5.5 mEq/L, temporary or permanent discontinuation or dose adjustment of the study drug due to hyperkalemia, or need for potassium-lowering therapy.	Up to 4 weeks after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Serum Potassium	Mean change in serum potassium from baseline to 4 weeks.	Baseline to 4 weeks
Time to First Hyperkalemia Event	Time from randomization to first occurrence of serum potassium ≥ 5.5 mEq/L.	Up to 4 weeks
Temporary or Permanent Discontinuation of Study Drug	Incidence of temporary or permanent interruption of study drug due to hyperkalemia.	Up to 4 weeks
Change in Albuminuria and in Renal Function	Change in urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) from baseline to 4 weeks.	Up to 4 weeks.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart Failure Hospitalization	Incidence of hospitalization due to heart failure.	Up to 4 weeks
All-Cause Mortality	Incidence of death from any cause.	Up to 4 weeks

Collaborators and Investigators

• Sponsor: Hospital de Messejana Dr. Carlos Alberto Studart Gomes

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: April 5, 2026
• First Submitted That Met QC Criteria: April 5, 2026
• First Posted (Actual): April 13, 2026

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 9, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Chronic Kidney Disease; Cardiorenal Syndrome; Hyperkalemia; Spironolactone; Mineralocorticoid Receptor Antagonist; Heart Failure Treatment; Finerenone
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Cardiovascular Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Heart Diseases; Chronic Disease; Disease Attributes; Metabolic Diseases; Diabetes Mellitus; Diabetes Complications; Renal Insufficiency; Water-Electrolyte Imbalance; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Heart Failure; Renal Insufficiency, Chronic; Diabetic Nephropathies; Hyperkalemia; Cardio-Renal Syndrome; Organic Chemicals; Polycyclic Compounds; Pregnanes; Steroids; Fused-Ring Compounds; Lactones; Pregnenes; Spironolactone; finerenone; Pharmaceutical Preparations
• Other Study ID Numbers: HM-IC-SAFEK

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No