Efficacy and Safety of Finerenone in Reducing Morbidity and Mortality in Heart Failure Patients with LVEF ≥40% Hospitalized for Acute Decompensated Heart Failure
- Trial ID
- 2023-508581-15-00
- Protocol
- 202301CPC
- Sponsor
- Colorado Prevention Center
Trial statistics
Objectives
The primary objective of this study is to evaluate whether **finerenone** reduces total heart failure (HF) events, including both first and subsequent occurrences, and cardiovascular (CV) death compared with placebo in patients hospitalized with acute decompensated heart failure with mid-range or preserved ejection fraction (HFmrEF/HFpEF). This is clinically relevant as it addresses the potential of finerenone to improve outcomes in a population at high risk for recurrent HF events and mortality, thereby potentially altering the management of heart failure.
Secondary objectives include determining the effects of finerenone compared with placebo on clinical events and changes in the Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS). This aims to assess the impact of finerenone on patient-reported outcomes and quality of life, which are important considerations in the comprehensive management of heart failure.
Participants
The clinical trial involves a total of **4064 participants** who are being studied to evaluate the effects of finerenone on heart failure events and cardiovascular death. The study population includes both **male and female** subjects, aged **18 years and older**, who have been hospitalized with acute decompensated heart failure with mildly reduced or preserved ejection fraction (**HFmrEF/HFpEF**). Participants were selected based on their current hospitalization or recent discharge with a primary diagnosis of heart failure, and they exhibit signs and symptoms of heart failure at the time of hospital admission. The trial includes individuals with elevated levels of N-terminal pro B-type natriuretic peptide (NTproBNP) or B-type natriuretic peptide (BNP), and those who have received at least one intravenous dose of a loop diuretic during their index hospitalization. The study population is characterized by a diverse range of individuals, including those from vulnerable populations, and encompasses a variety of lifestyle factors, although specific lifestyle considerations such as diet or physical activity are not detailed. The trial's inclusion criteria ensure that participants are stabilized prior to randomization, with specific requirements regarding blood pressure, diuretic use, and the absence of certain intravenous treatments. Women of childbearing potential are included only if they have a negative pregnancy test and agree to use adequate contraception throughout the study.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy and safety of **finerenone** in patients with heart failure with preserved or mildly reduced ejection fraction, specifically those hospitalized due to acute decompensated heart failure. This is a randomized, double-blind, placebo-controlled study, which will involve the administration of **finerenone** in the form of film-coated tablets. The trial is expected to commence on May 15, 2024, and conclude by April 3, 2026, with a maximum treatment period of 30 days for each participant.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, recent hospitalization for heart failure, and specific clinical and laboratory parameters. Following randomization, participants will receive either **finerenone** or placebo, administered orally. The study will include follow-up visits to monitor the participants' health status, adherence to the treatment regimen, and any adverse events. The primary endpoint is a composite of total heart failure events and cardiovascular death, with secondary endpoints including time to first occurrence of cardiovascular death or heart failure event, total heart failure events, and changes in health status as measured by the Kansas City Cardiomyopathy Questionnaire.
The expected length of participant involvement is approximately 30 days, with conditions for early termination including significant adverse events, withdrawal of consent, or non-compliance with the study protocol. The trial aims to provide valuable insights into the potential benefits of **finerenone** in reducing heart failure events and improving survival in this patient population.
Treatment
The clinical trial involves the administration of **Finerenone**, a chemical compound provided in the form of a **film-coated tablet**. The pharmaceutical product is manufactured by Bayer AG and is identified by the sponsor product code BAY 94-8862. The active substance, finerenone, is administered orally. The trial includes three different dosing regimens: a maximum daily dose of 40 mg, 20 mg, and 10 mg, with corresponding maximum total doses of 36 g, 18 g, and 9 g, respectively. Each dosing regimen is maintained for a maximum treatment period of 30 days. The administration schedule is designed to evaluate the efficacy and safety of finerenone in reducing heart failure events and cardiovascular death among patients with heart failure with preserved ejection fraction (HFpEF) or heart failure with mid-range ejection fraction (HFmrEF) who have been hospitalized due to acute decompensated heart failure.
In addition to the experimental treatment, a **placebo** is utilized as a comparator in the study. The placebo is designed to match the experimental medication in appearance and administration route, ensuring blinding of participants and investigators. The placebo is administered orally in a similar dosing schedule to the active treatment groups, allowing for a direct comparison of outcomes between the finerenone and placebo groups. Compliance with the dosing regimen is monitored throughout the study to ensure adherence and accurate assessment of the treatment's effects.
Efficacy
The efficacy of **finerenone** in the clinical trial will be assessed using a composite primary endpoint, which includes total (first and subsequent) heart failure (HF) events, such as HF hospitalization or urgent visits for worsening HF, and cardiovascular (CV) death. Secondary endpoints will evaluate treatment group differences in several parameters: time to first occurrence of the composite of CV death or HF event, total HF events, change from baseline to month 6 in the Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS), time to CV death, and time to death from any cause.
Measurements for these endpoints will be collected at specified timepoints throughout the trial, with particular attention to changes from baseline to month 6 for the KCCQ-TSS. The trial is designed to determine whether **finerenone** reduces total HF events and CV death compared to placebo in patients hospitalized with acute decompensated heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF). The trial will follow a structured schedule for data collection and analysis to ensure the reliability and validity of the efficacy assessments.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Age ≥18 years or legal age of majority if >18 years in the participant’s country of residence.
- Current hospitalization or recently discharged (during or within 30 days of discharge) with a primary diagnosis of acute HF.
- Heart failure signs and symptoms at the time of hospital admission, including: a. Symptoms (at least one of the following): persistent dyspnea at rest or with minimal exertion worse than baseline, or new or worsening orthopnea b. Signs 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
- 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
- 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).
- 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
- Treatment during the index hospitalization with at least 1 intravenous dose of a loop diuretic, e.g. furosemide, torsemide, bumetanide
- 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
- Provide written informed consent.
Exclusion Criteria
- 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).
- 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
- 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.
- Participation in another interventional clinical study or treatment with another investigational medicine or device within 30 days prior to randomization
- 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.
- eGFR <25 mL/min/1.73m² or potassium >5.0 mmol/L at screening.
- 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).
- 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
- 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)
- 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
- 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
- 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.
- Known hypersensitivity to the IP (active substance or excipients).
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Austria | Not Yet Recruiting | 15 May 2024 | 50 |
 Bulgaria | Not Yet Recruiting | 15 May 2024 | 260 |
 Croatia | Recruiting | 15 May 2024 | 134 |
 Czechia | Recruiting | 15 May 2024 | 146 |
 Germany | Recruiting | 15 May 2024 | 60 |
 Greece | Recruiting | 15 May 2024 | 84 |
 Hungary | Recruiting | 15 May 2024 | 192 |
 Italy | Recruiting | 15 May 2024 | 60 |
 Latvia | Not Yet Recruiting | 15 May 2024 | 68 |
 Lithuania | Recruiting | 15 May 2024 | 108 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
BAY 94-8862 | Test | FILM-COATED TABLET | ORAL | 20 | 30 | PRD1624191 |
BAY 94-8862 coated tablet | Placebo | N/A | — | — | — | N/A |
Finerenone | Test | FILM COATED TABLET | ORAL | 10 | 30 | PRD9408175 |
Finerenone | Test | FILM COATED TABLET | ORAL | 40 | 30 | PRD9408174 |