Study to Evaluate the Efficacy (Effect on Disease) and Safety of Finerenone on Morbidity (Events Indicating Disease Worsening) & Mortality (Death Rate) in Participants With Heart Failure and Left Ventricular Ejection Fraction (Proportion of Blood Expelled Per Heart Stroke) Greater or Equal to 40%

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of finerenone compared to placebo (a tablet without active substance) in the reduction of cardiovascular death (generally meaning death due to disease of the heart or blood vessels) and total Heart Failure (HF) events, including HF hospitalization and urgent visits for HF(generally meaning a hospital stay or urgent presentation to a healthcare unit due to worsening symptoms of heart failure) in patients suffering from HF with an ejection fraction greater than or equal to 40%. Researchers will also collect information on how much the heart disease has impact on patient's lives, change of kidney function, and how well finerenone treatment is tolerated. The study plans to enroll 6000 male and female patients of the age of 40 years and above suffering from heart failure with ejection fraction greater than or equal to 40%. Participants will take the study product as oral tablet with a dose between 0 (Placebo) 40 mg once daily. Study duration will be up to 43 months.

Official Title
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A Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Study to Evaluate the Efficacy and Safety of Finerenone on Morbidity and Mortality in Participants With Heart Failure (NYHA II-IV) and Left Ventricular Ejection Fraction ≥ 40% (LVEF ≥ 40%)

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: Finerenone (BAY94-8862)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant (male or female) must be aged 40 years and older. Diagnosis of heart failure with New York Heart Association(NYHA) class II-IV, ambulatory or hospitalized primarily for heart failure. On diuretic treatment for at least 30 days prior to randomization. Documented left ventricular ejection fraction (LVEF) of ≥40% measured by any modality within the last 12 months. Structural heart abnormalities based on any local imaging measurement within the last 12 months, defined by at least one of the following findings: left atrial diameter (LAD) ≥3.8cm, left atrial area (LAA) ≥20cm2, left atrial volume index (LAVI) >30 mL/m2, left ventricular mass index (LVMI) ≥115 g/m2 (♂)/ 95 g/m2 (♀), septal thickness or posterior wall thickness ≥1.1 cm n-terminal prohormone B-type natriuretic peptide (NT-proBNP) ≥300 pg/mL (BNP ≥100 pg/mL) in sinus rhythm and patient does not have an ongoing diagnosis of paroxysmal atrial fibrillation or NT-proBNP ≥900 pg/mL (BNP ≥300 pg/mL) in atrial fibrillation (or if atrial fibrillation status is unknown or if patient has an ongoing diagnosis of paroxysmal atrial fibrillation) for participants obtained at the following time: Within 90 days prior to randomization if patient had been hospitalized for heart failure (HF) requiring initiation or change in HF therapy or if patient had an urgent visit for HF requiring intravenous (IV) diuretic therapy, both within 90 days prior to randomization OR Within 30 days prior to randomization if patient has not been hospitalized for HF nor had an urgent HF visit within the past 90 days. Women of childbearing potential can only be included in the study if a pregnancy test is negative at screening and baseline and if they agree to use adequate contraception which is consistent with local regulations regarding the methods for contraception for those participating in clinical trials. Exclusion Criteria: Estimated glomerular filtration rate (eGFR) <25 mL/min/1.73 m² at either screening or randomization visit. Serum/plasma potassium >5.0 mmol/L at either screening or randomization visit. Acute inflammatory heart disease, e.g. acute myocarditis, within 90 days prior to randomization Myocardial infarction or any event which could have reduced the ejection fraction within 90 days prior to randomization Coronary artery bypass graft surgery in the 90 days prior to randomization Percutaneous coronary intervention in the 30 days prior to randomization Stroke or transient ischemic cerebral attack within 90 days prior to randomization Probable alternative cause of participants' HF symptoms that in the opinion of the investigator primarily accounts for patient's dyspnea such as significant pulmonary disease, anemia or obesity. Specifically, patients with the below are excluded: Severe pulmonary disease requiring home oxygen, or chronic oral steroid therapy, History of primary pulmonary arterial hypertension, Hemoglobin <10 g/dl, Valvular heart disease considered by the investigator to be clinically significant, Body Mass Index (BMI) >50 kg/m2 at screening Systolic blood pressure(SBP) ≥160 mmHg if not on treatment with ≥3 blood pressure lowering medications or ≥180 mmHg irrespective of treatments, on 2 consecutive measurements at least 2-minute apart, at screening or at randomization. Concomitant systemic therapy with potent cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitors (e.g. itraconazole, ritonavir, indinavir, cobicistat, clarithromycin) or moderate or potent CYP3A4 inducers, that cannot be discontinued 7 days prior to randomization and for the duration of the treatment period.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1_BAY94-8862<br>Adult patients receive BAY94-8862 | Drug: Finerenone (BAY94-8862)<br>* For participants with an eGFR ≤60 mL/min/1.73 m^2: Starting dose is 10 mg OD and maximum dose 20 mg OD. For participants with an eGFR >60 mL/min/1.73 m^2: Starting dose is 20 mg OD and maximum dose 40 mg OD. Finerenone is administered orally as immediate release tablets.<br>|
| Placebo Comparator: Arm 2_Placebo<br>Adult patients receive placebo | Other: Placebo<br>* Placebo tablets matching BAY94-8862 are administered orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of cardiovascular deaths and heart failure events | Composite endpoint. Heart Failure events comprise first and recurrent events | Up to 42 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to total (first and recurrent) HF events |  | Up to 42 months | 
| Improvement in NYHA class from Baseline to Month 12 |  | Up to 12 month after start of treatment | 
| Change in Total Symptom Score (TSS) from KCCQ. | Patient Reported Outcomes measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) | At baseline, Months 6, 9 and 12 | 
| Time to first occurrence of composite renal endpoint | Composite renal endpoint: sustained decrease in estimated glomerular filtration rate (eGFR) ≥50% relative to baseline over at least 4 weeks, or sustained eGFR decline to <15ml/min/1.73m2 or initiation of dialysis or renal transplantation. | Up to 42 months | 
| Time to death from any cause |  | Up to 42 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Failure with Preserved Ejection Fraction,, Mineralocorticoid receptor antagonist (MRA)