A Study to Determine the Efficacy and Safety of Finerenone on Morbidity and Mortality Among Hospitalized Heart Failure Patients

Study Overview
=================
Brief Summary
-----------------
Finerenone will be compared to placebo to determine efficacy and safety of treatment in patients hospitalized with acute decompensated heart failure (HF) and mildly reduced or preserved left ventricular ejection fraction.

Detailed Description
-----------------
This is an international, randomized, double-blind, placebo-controlled, event-driven trial of finerenone for the treatment hospitalized heart failure patients with mildly reduced or preserved ejection fraction.

Official Title
-----------------
Randomized Trial to Determine the Efficacy and Safety of Finerenone on Morbidity and Mortality Among Heart Failure Patients With Left Ventricular Ejection Fraction Greater Than or Equal to 40% Hospitalized Due to an Episode of Acute Decompensated Heart Failure (REDEFINE-HF)

Conditions
-----------------
Heart Failure, Acute Heart Failure

Intervention / Treatment
-----------------
* Drug: Finerenone
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Provide electronic or written informed consent, either personally or through a legally authorized representative Age ≥18 years Current hospitalization or recently discharged with the primary diagnosis of heart failure Heart failure signs and symptoms at the time of hospital admission Imaging evidence of mildly reduced or preserved left ventricular ejection fraction (EF) (40% or higher) Elevated N-terminal pro B-type natriuretic peptide (NTproBNP) ≥1000 pg/mL or B-type natriuretic peptide (BNP) ≥250 pg/mL for patients without atrial fibrillation (AF); or elevated NTproBNP ≥2000 pg/mL or BNP ≥500 pg/mL for patients with AF Exclusion Criteria: Treatment with a mineralocorticoid receptor antagonist (MRA) Documented prior history of severe hyperkalemia in the setting of MRA use Estimated glomerular filtration rate (eGFR) <25 mL/min/1.73m² or serum/plasma potassium >5.0 mmol/L at screening Acute myocardial infarction, coronary revascularization, valve replacement/repair, or implantation of a cardiac resynchronization therapy device within 30 days Hemodynamically significant (severe) uncorrected primary cardiac valvular disease Cardiomyopathy due to known acute inflammatory heart, infiltrative diseases, accumulation diseases, muscular dystrophies, cardiomyopathy with reversible causes, known hypertrophic obstructive cardiomyopathy, complex congenital heart disease, or known pericardial constriction Probable alternative cause of participant's heart failure symptoms Concomitant systemic therapy with potent cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitors or moderate CYP3A4 inducers, or potent CYP3A4 inducers

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Finerenone<br> | Drug: Finerenone<br>* Oral finerenone<br>* Other names: Kerendia;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Matching oral placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite total of HF events and cardiovascular (CV) death. | Total (first and subsequent) HF hospitalizations, urgent visits for worsening HF, and CV deaths with finerenone compared to placebo. | Ongoing, up to  30 months | 
| Number of serious adverse events. | Occurrence of serious adverse events (excluding efficacy endpoints) with finerenone compared to placebo. | Ongoing, up to  30 months | 
| Number of adverse events leading to discontinuation of study drug. | Occurrence of adverse events leading to study drug discontinuation with finerenone compared to placebo. | Ongoing, up to  30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first occurrence of the composite of CV death or HF event. | Time to first occurrence of the composite of CV death or HF event with finerenone compared to placebo. | Ongoing, up to  30 months | 
| Total HF events. | Total HF events with finerenone compared to placebo. | Ongoing, up to  30 months | 
| Change from baseline in the Total Symptom Score on the Kansas City Cardiomyopathy Questionnaire (KCCQ-TSS) at Month 6. |  | 6 Months | 
| Time to CV death. | Time to CV death with finerenone compared to placebo. | Ongoing, up to  30 months | 
| Time to death from any cause. | Time to death from any cause with finerenone compared to placebo. | Ongoing, up to  30 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Heart failure, Preserved ejection fraction, Mildly reduced ejection fraction, Hospitalized