Efficacy and Safety With Early Treatment of Finerenone in... | NCT07397650

Label	Type	Description	Intervention Names
Finerenone	Experimental	Patients will be randomized 1:1 to either finerenone or placebo.	Drug: Finerenone Oral Tablet
Placebo	Placebo Comparator	Placebo tablets matching finerenone are administered orally	Drug: Finerenone Placebo

Name	Type	Description	Arm Group Labels	Other Names
Finerenone Oral Tablet	Drug	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.

Measure	Description	Time Frame
A hierarchical composite endpoint of death and worsening heart failure	A hierarchical composite endpoint consisting of death, worsening HF during hospitalization, HF rehospitalization, worsening HF after discharge requiring IV diuretic or sustained intensification of oral therapy, and change in N-terminal pro-B-type natriuretic peptide levels at 12 weeks as assessed using a win ratio	Up to 12 weeks

Measure	Description	Time Frame
All-cause death		Up to 12 weeks
Cardiovascular death		Up to 12 weeks
Worsening HF during hospitalization

Eligibility Module

Eligibility Criteria

Patients eligible for inclusion in this study meet all of the following criteria: Inclusion Criteria:

Patients ≥18 years of age, male or female
Current hospitalization with AHF requiring intravenous loop diuretics or vasodilators during the index admission
Patients have to have at least one of new or worsening symptoms due to HF and one of new or worsening physical examination findings due to HF (i) symptom dyspnoea, decreased exercise tolerance, or fatigue (ii) physical examination peripheral edema, increasing abdominal distention or ascites, pulmonary rales/crackles/crepitations, increased jugular venous pressure and/or hepatojugular reflux, S3 gallop, clinically significant or rapid weight gain
Patients who are not hemodynamically unstable as defined by meeting the following criteria 
1. Systolic blood pressure ≥100 mmHg and no symptoms of hypotension within 6 hours prior to randomization 
2. No increase in intravenous diuretic dose or intravenous vasodilators within 6 hours prior to randomization with worsening HF symptom 
3. Without cardiogenic shock, no use of inotropes or vasopressors, no use of mechanical circulatory support, not requiring intubation after admission, and not expected to require inotropes, vasopressors, mechanical circulatory support or intubation during the index hospitalization
NTproBNP ≥1500 pg/mL or BNP ≥375 pg/mL (For patients treated with ARNI in the previous 4 weeks prior to randomization, only NT-proBNP values should be used)
Most recent LVEF ≥40% within the past 1 year
Randomization within 24 hours after admission, and drug administration within 36 hours after admission
Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
Signed informed consent must be obtained prior to participation in the study

Exclusion Criteria:

Estimated glomerular filtration rate (eGFR) <25 mL/min/1.73m2 by CKD-EPI Creatinine Equation (2021) at screening
Serum/plasma potassium >5.0 mmol/L at screening
Patients who cannot receive oral treatment
Use of eplerenone, spironolactone, esaxerenone or potassium-sparing diuretic within 30 days before randomization
Known hypersensitivity to the study intervention (active substance or excipients)
Systemic therapy with potent cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitors or inducers within 7 days before randomization or is expected to be used during the study period (e.g. itraconazole, ritonavir, indinavir, cobicistat, clarithromycin).
Participants who require treatment with more than one ACEI, ARB or angiotensin-receptor neprilysin inhibitor (ARNI) simultaneously
Acute heart failure in which other diseases are the main cause of symptoms and signs (chronic obstructive pulmonary disease, anemia, etc.)
Patients who are on dialysis including peritoneal dialysis or in whom the initiation of dialysis during the study period
Pregnant or lactating female
Acute coronary syndrome, pulmonary thromboembolism, stroke, or transient ischemic attack within 90 days before randomization.
Have undergone the following therapeutic intervention within 30 days before randomization: cardiovascular surgery (e.g., coronary artery bypass grafting, surgery for valvular heart disease, transcatheter aortic valve implantation, percutaneous coronary intervention, percutaneous edge-to-edge mitral valve repair, and other types of surgery at the investigator's discretion) and implantation of an implantable defibrillator, or a cardiac resynchronization therapy defibrillator.
Heart transplant recipients or patients listed for heart transplantation who are expected to undergo transplantation during the study, patients implanted with an implantable ventricular-assist device, patients expected to require an implantable ventricular-assist device during the study, and patients expected to switch to palliative care during the study.
Coronary or valvular heart disease likely to require surgical or percutaneous intervention within the study period (there is no reason to exclude secondary mitral or tricuspid regurgitation due to reduced cardiac function, except for the absence of a plan to perform cardiac surgery or therapeutic catheterization)
Secondary cardiomyopathy such as amyloidosis, cardiac sarcoidosis, hemochromatosis, Fabry's disease, chemotherapy induced cardiomyopathy, and muscular dystrophy. Heart failure due to takotsubo cardiomyopathy, obstructive hypertrophic cardiomyopathy, complex congenital heart disease (as determined by the investigator), pericardial constriction, right heart failure in absence of left-sided structural disease
Acute cardiac structural abnormalities (e.g., acute mitral regurgitation due to ruptured chordae tendineae and infective endocarditis)
Peripartum cardiomyopathy diagnosed within 6 months before randomization.
Active myocarditis at randomization.
Patients with symptomatic bradycardia or complete atrioventricular block who are being treated with temporary pacemaker implantation at the time of admission, or who are expected to require temporary or permanent pacemaker implantation in the future. Patients who have already been treated with permanent pacemaker implantation do not meet the exclusion criteria
Presence of uncontrolled thyroid disease
Addison's disease
Hepatic insufficiency classified as Child-Pugh C
Patients with excessive alcohol intake (15+ drinks/week for men, 8+ drinks/week for women)
Any other condition or therapy, which would make the participant unsuitable for this study and will not allow participation for the full planned study period (e.g. active malignancy or other condition limiting life expectancy to less than 12 months)
Patients with dementia. If a sub-investigator determines that confirmation of cognitive impairment is necessary, it must be verified that the Mini-Cog score is not less than 4.
Participation in another interventional clinical study (e.g. phase 1 to 3 clinical studies) or treatment with another investigational medicinal product within 30 days prior to randomization.Other conditions likely to interfere with the patient's safety or compliance with the protocol
Patients deemed unsuitable by the principal investigator or sub investigator