Resumen

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.

Elegibilidad

Edad mínima: 40 YearsSexo: ALL

Criterios de inclusión

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.

Criterios de exclusión

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.

Intervenciones

drug

Finerenone (BAY94-8862)

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.

other

Placebo

Placebo tablets matching BAY94-8862 are administered orally.

Ubicaciones

Centro de Investigaciones Metabolicas | Ciudad de Autonoma de Buenos Aires, Argentina

Ciudad Autónoma de Buenos Aire, Buenos Aires, Argentina

Clínica Coronel Suarez

Coronel Suárez, Buenos Aires, Argentina

Hospital Italiano de La Plata | Clinical Research Department

La Plata, Buenos Aires, Argentina

Centro de Investigaciones Medicas Lanus | Buenos Aires, Argentina

Lanús, Buenos Aires, Argentina

Sanatorio Modelo Quilmes

Quilmes, Buenos Aires, Argentina

Corporación Médica de General San Martín

San Martín, Buenos Aires, Argentina

Instituto De Investigaciones Clinicas Zarate | Zarate, Argentina

Zárate, Buenos Aires, Argentina

Instituto Cardiovascular de Buenos Aires | Buenos Aires, Argentina

Buenos Aires, Buenos Aires F.D., Argentina

Hospital Militar Central "CIR. MY. C. Argerich"

Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina

Centro de Especialidades Medicas (CEMEDIC)

Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina

CEDIC Centro de Investigación Clínica | Buenos Aires, Argentina

CABA, Ciudad Auton. de Buenos Aires, Argentina

Grupo Orono | Instituto Cardiovascular de Rosario - Insuficiencia Cardiaca y Trasplante Department

Rosario, Santa Fe Province, Argentina

Consultorios Integrados Rosario | Instituto Medico de la Fundacion de Estudios Clinicos

Rosario, Santa Fe Province, Argentina

Instituto de Cardiologia | Tucuman, AR

San Miguel de Tucumán, Tucumán Province, Argentina

Investigaciones Medicas IMOBA S.R.L.

Buenos Aires, Argentina

Instituto de Cardiologia de Corrientes Juana F. Cabral | Corrientes, Argentina

Corrientes, Argentina

Clínica Privada del Prado

Córdoba, Argentina

Instituto Médico DAMIC- Fundación Rusculleda