Acute Heart Failure Finerenone, Acute Heart Failure
Conditions
Interventions
Finelenone administered early in hospitalization in patients with acute heart failure with LVEF of 40% or greater
Sponsors
Matsue Yuya
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients eligible for inclusion in this study meet all of the following criteria: 1.Patients >=18 years of age, male or female 2.Patients currently hospitalized for AHF who require intravenous loop diuretics or vasodilators during the index admission 3.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 4.Patients who are not hemodynamically unstable as defined by meeting the following criteria a.Systolic blood pressure >=100 mmHg and no symptoms of hypotension within 6 hours prior to randomization b.No increase in intravenous diuretic dose or intravenous vasodilators within 6 hours prior to randomization with worsening HF symptom c.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 5.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) 6.Most recent LVEF >=40% within the past 1 year 7.Randomization within 24 hours after presentation, and drug administration within 36 hours after presentation 8.Patients who have given written consent to participate in the study
Exclusion criteria
Exclusion criteria: 1.Estimated glomerular filtration rate (eGFR) 5.0 mmol/L at screening 3.Patients who cannot receive oral treatment 4.Use of eplerenone, spironolactone, esaxerenone, or potassium-sparing diuretic within 30 days before randomization 5.Known hypersensitivity to the study intervention (active substance or excipients) 6.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). 7.Participants who require treatment with more than one ACEI, ARB or angiotensin-receptor neprilysin inhibitor (ARNI) simultaneously 8. Acute heart failure in which other diseases are the main cause of symptoms and signs (chronic obstructive pulmonary disease, anemia, etc.) 9.Patients who are on dialysis including peritoneal dialysis or in whom the initiation of dialysis during the study period 10.Pregnant or lactating female 11.Acute coronary syndrome, pulmonary thromboembolism, stroke, or transient ischemic attack within 90 days before randomization. 12.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. 13.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. 14.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) 15.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 16.Acute cardiac structural abnormalities (e.g., acute mitral regurgitation due to ruptured chordae tendineae and infective endocarditis) 17.Peripartum cardiomyopathy diagnosed within 6 months before randomization. 18.Active myocarditis at randomization. 19.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 20.Presence of uncontrolled thyroid disease 21.Addison's disease 22.Hepatic insufficiency classified
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Hierarchical composite up to 12 weeks: (i) all-cause death at 12 weeks, (ii) worsening HF during hospitalization a)initiation of inotropic therapy b)mechanical circulatory support c)invasive ventilatory support for heart failure (iii) HF rehospitalization up to 12 weeks, (iv) Worsening HF after discharge requiring IV diuretic or sustained intensification of oral therapy up to 12 weeks, (v) NT-proBNP change from baseline to 12 weeks (continuous variable). | — |
Secondary
| Measure | Time frame |
|---|---|
| 1.All-cause death up to 12 weeks 2.Cardiovascular death up to 12 weeks. 3.Worsening HF during hospitalization 4.HF rehospitalization up to 12 weeks 5.Worsening HF after discharge requiring IV diuretic or sustained intensification of oral therapy up to 12 weeks 6.NT-proBNP change from baseline to 12 weeks 7.KCCQ-TSS change from baseline to 12 weeks 8.Urine output from randomization to 48 hours 9.Change in patient dyspnea in the supine position assessed by a visual analogue scale from randomization to discharge and to 12 weeks 10.Symptomatic atrial fibrillation up to discharge and up to 12 weeks | — |
Contacts
Public ContactYuya Matsue
Juntendo University Hospital
Outcome results
None listed