FINERENONE for Heart failure (HFmrEF/HFpEF)

Inclusion criteria

• {"criterion_text":"- 2. Age ≥18 years or legal age of majority if >18 years in the participant’s country of residence.\n- 3. Current hospitalization or recently discharged (during or within 30 days of discharge) with a primary diagnosis of acute HF.\n- 4. Heart failure signs and symptoms at the time of hospital admission, including: a.\tSymptoms (at least one of the following): persistent dyspnea at rest or with minimal exertion worse than baseline, or new or worsening orthopnea b.\tSigns of fluid overload (at least one of the following): congestion on chest X-ray, rales on chest auscultation, clinically relevant edema (as judged by the investigator), elevated jugular venous pressure\n- 5. Imaging evidence of mildly reduced or preserved EF (40% or higher) per local reading on the most recent assessment, preferably measured during current hospitalization; a historical left ventricular EF (LVEF) assessment may be used if there is no in-hospital measurement and if it was measured within 12 months prior to screening provided there was no major intervening event affecting EF such as an MI\n- 6. Elevated N-terminal pro B-type natriuretic peptide (NTproBNP) ≥500 pg/mL or B-type natriuretic peptide (BNP) ≥125 pg/mL according to the local lab for patients without atrial fibrillation (AF); or elevated NTproBNP ≥1500 pg/mL or BNP ≥375 pg/mL for patients with AF, measured during the current hospitalization, in the 72 hours prior to hospital admission, or during the 30 days post-discharge. (Note: for patients treated with an angiotensin receptor neprilysin inhibitor [ARNI] in the previous 4 weeks prior to randomization, NTproBNP values should be used where available).\n- 7. Fulfillment of the following stabilization criteria (if randomized during hospitalization): a. Systolic blood pressure (BP) ≥100 mmHg and no symptoms of hypotension in the 6 hours prior to randomization b. No increase in intravenous diuretic dose for 6 hours prior to randomization c. No intravenous vasodilators, including nitrates, within the last 6 hours prior to randomization d. No intravenous inotropic drugs or mechanical circulatory support for 24 hours prior to randomization\n- 8. Treatment during the index hospitalization with at least 1 intravenous dose of a loop diuretic, e.g. furosemide, torsemide, bumetanide\n- 9. Women of childbearing potential can only be included in the study if a pregnancy test is negative at screening and if they agree to use adequate contraception which is consistent with local regulations regarding the methods for contraception for the duration of the study\n- 1. Provide written informed consent."}

Exclusion criteria

• {"criterion_text":"- 1. Currently on or planned for long-term therapy with an MRA (finerenone, spironolactone, eplerenone, canrenone, esaxerenone); treatment with MRA should not be interrupted for the purpose of enrollment into the study. (Note: patients with recent MRA exposure should not be randomized/receive study treatment until 7 days from the last dose to allow adequate washout).\n- 7. Cardiomyopathy due to known acute inflammatory heart disease (e.g., acute myocarditis within 90 days prior to randomization), infiltrative diseases (e.g., amyloidosis), accumulation diseases (e.g., haemochromatosis, Fabry disease), muscular dystrophies, cardiomyopathy with reversible causes (e.g., stress cardiomyopathy), known hypertrophic obstructive cardiomyopathy, complex (according to investigator`s judgement) congenital heart disease, or known pericardial constriction\n- 8. Probable alternative cause of participant’s HF symptoms that, in the opinion of the investigator, primarily accounts for patient’s symptoms; specifically, patients with severe pulmonary disease requiring home oxygen or chronic oral steroid therapy, primary pulmonary arterial hypertension at screening\n- 9. Concomitant systemic therapy with potent cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitors (e.g., itraconazole, ritonavir, indinavir, cobicistat, clarithromycin), or moderate CYP3A4 inducers (e.g., efavirenz, phenobarbital), or potent CYP3A4 inducers (e.g., carbamazepine, phenytoin, St John’s Wort) that cannot be discontinued 7 days prior to randomization and for the duration of the treatment period (note: a list of excluded CYP3A4 inhibitors and inducers is provided in Appendix D.\n- 11. Known hypersensitivity to the IP (active substance or excipients).\n- 10. Concomitant treatment with renin inhibitor, more than one angiotensin converting enzyme inhibitor (ACEi), angiotensin receptor blocker (ARB) or ARNI, or with a potassium-sparing diuretic that cannot be stopped prior to randomization and for the duration of the treatment period\n- 12. Any other condition or therapy (e.g., breastfeeding, cardiogenic shock, clinically overt severe hepatic insufficiency, Addison’s disease, or other severe condition as per investigator’s judgment such as disease with <1 year life expectancy) which would make the participant unsuitable for this study and not allow participation for the full planned study period.\n- 13. Participation in another interventional clinical study or treatment with another investigational medicine or device within 30 days prior to randomization\n- 2. Documented prior history of severe hyperkalemia (potassium ≥6.0 mmol/L and/or resulting in hospitalization or Emergency Department visit) in the setting of MRA use.\n- 3. eGFR <25 mL/min/1.73m² or potassium >5.0 mmol/L at screening.\n- 4. Acute MI due to plaque rupture, coronary revascularization, valve replacement/repair, or implantation of a cardiac resynchronization therapy device within 30 days prior to randomization (Note: pacemakers or implantable cardioverter defibrillators without resynchronization function are allowed).\n- 5. Prior heart transplant or listed for heart transplant with expectation to receive a transplant during the course of this trial (according to investigator judgement), or planned for palliative care for HF, or currently using or plan for mechanical circulatory support, e.g., left ventricular assist device, intra-aortic balloon pump, or patients on mechanical ventilation or patients with planned outpatient inotropic support\n- 6. Hemodynamically significant (severe) uncorrected primary cardiac valvular disease considered by the investigator to be the primary cause of heart failure (note: secondary mitral regurgitation or tricuspid regurgitation due to dilated cardiomyopathy is not excluded unless planned for surgery or intervention during the course of the study)"}

Primary endpoints

• {"endpoint_text":"- The primary study endpoint is a composite of total (first and subsequent) HF events (HF hospitalization or urgent visit for worsening HF) and CV death.","definition_or_measurement_approach":"Composite endpoint defined as total (first and subsequent) heart failure events (HF hospitalization or urgent visit for worsening HF) plus cardiovascular (CV) death; events are counted as time-to-event and as total event counts according to study endpoint definition."}

Secondary endpoints

• {"endpoint_text":"- Secondary endpoints include treatment group difference in: 1.Time to first occurrence of the composite of CV death or HF event; 2. Total HF events; 3. Change from baseline to month 6 in KCCQ-TSS; 4. Time to CV death 5.\tTime to death from any cause","definition_or_measurement_approach":"Endpoints comprise (1) time-to-first-event for composite of CV death or HF event (time-to-event analysis), (2) total HF events (count of first and subsequent HF events), (3) change from baseline to month 6 in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS), (4) time to CV death (time-to-event), (5) time to death from any cause (time-to-event)."}

Primary sponsor

Full Name

Colorado Prevention Center

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

United States

Contract research organisations

Name

Emerald Clinical Trials B.V.

Responsibilities

Vendor Management; CDA and CTA execution, Investigator payments, EC/ IRB submissions; Regulatory management

Name

SanaClis s.r.o.

Responsibilities

Vendor Management (payment reimbursement)

Third parties

• {"country":"Netherlands","full_name":"Emerald Clinical Trials B.V.","duties_or_roles":"Vendor Management; CDA and CTA execution, Investigator payments, EC/ IRB submissions; Regulatory management","organisation_type":"Pharmaceutical company"}
• {"country":"Slovakia","full_name":"SanaClis s.r.o.","duties_or_roles":"Vendor Management (payment reimbursement) and related operational support","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Bayer AG","duties_or_roles":"Site management; Site Identification/ investigator identification; Site Selection; Site Initiation Visit performing, Site activation, Site close out, Source Data Verification","organisation_type":"Pharmaceutical company"}