A study to gather information on the influence of study drug finerenone on the number of deaths and hospitalizations in participants with heart failure.

Phase 1

Conditions: Heart failure
MedDRA version: 20.0Level: LLTClassification code 10019279Term: Heart failureSystem Organ Class: 100000004849
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Registration Number: EUCTR2020-000306-29-CZ

Lead Sponsor: Bayer AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 5500

Inclusion Criteria

1. Participant (male or female) must be aged 40 years and older, at the time of signing the informed consent.
2. Diagnosis of heart failure with NYHA class II–IV, ambulatory or hospitalized primarily for heart failure.
3. Treated with diuretics within 30 days prior to randomization.
4. Documented LVEF of =40% measured by any modality within the last 12 months.
5. Structural heart abnormalities based on any local imaging measurement within the last 12 months, defined by at least one of the following findings: LAD =3.8cm, LAA =20cm² , LAVI >30 mL/m² , LVMI =115 g/m² (?)/ 95 g/m² (?), septal thickness or posterior wall thickness =1.1 cm.
6. NT-proBNP =300 pg/mL (BNP = 100 pg/mL) in SR and patient does not have an ongoing diagnosis of paroxysmal atrial fibrilation or NT-proBNP =900pg/mL (BNP = 300 pg/mL) in AF (or if atrial fibrilation status is unknown or if patient has an ongoing diagnosis of paroxysmal atrial fibrilation) for participants obtained at the following time:
- Within 90 days prior to randomization if patient had been hospitalized for 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.
7. 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.
8. 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1500
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4000

Exclusion Criteria

1. eGFR <25 mL/min/1.73 m² at either screening or randomization visit.
2. Serum/plasma potassium >5.0 mmol/L at either screening or randomization visit.
3. Acute inflammatory heart disease, e.g. acute myocarditis, within 90 days prior to randomization
4. Myocardial infarction or any event which could have reduced the ejection fraction within 90 days prior to randomization
5. Coronary artery bypass graft surgery in the 90 days prior to randomization
6. Percutaneous coronary intervention in the 30 days prior to randomization
7. Stroke or transient ischemic cerebral attack within 90 days prior to randomization
8. 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
- BMI >50 kg/m2 at screening
9. 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
10. Life-threatening or uncontrolled arrhythmias at screening and/or randomization including but not limited to sustained ventricular tachycardia and atrial fibrillation, or atrial flutter with resting ventricular rate >110 bpm
11. Symptomatic hypotension with mean systolic blood pressure <90 mmHg at screening or at randomization
12. Any primary cause of HF scheduled for surgery, e.g. valve disease such as severe aortic stenosis or severe mitral regurgitation by the time of screening or randomization
13. History of peripartum cardiomyopathy, chemotherapy induced cardiomyopathy, viral myocarditis, right heart failure in absence of left-sided structural disease, pericardial constriction, genetic hypertrophic cardiomyopathy, or infiltrative
cardiomyopathy including amyloidosis
14. Presence of left ventricular assist device by the time of screening or randomization
15. History of hyperkalemia or acute renal failure during MRA treatment for >7 consecutive days, leading to permanent discontinuation of the MRA treatment
16. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotrophin urine or serum test
17. Known hypersensitivity to the study intervention (active substance or excipients)
18. Hepatic insufficiency classified as Child-Pugh C at screening or randomization
19. Addison’s disease
20. Requirement of any IV vasodilating drug (e.g. nitrates, nitroprusside), any IV natriuretic peptide (e.g. nesiritide, carperitide), any IV positive inotropic agents, or mechanical support (intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, or any ventricular assist device) within 24 hours prior to randomization
21. Participants who require treatment with more than one ACEI, ARB or angiotensin-receptor neprilysin inhibitor (ARNI), or two simultaneously at randomization
22. Continuous (at least 90 days) treatment with an MRA (e.g. spironolactone, eplerenone, canrenone, esaxerenone) within 12 months prior to screening. Last intake at least 30 days before randomization. Tre

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To demonstrate the superiority of finerenone to placebo in reducing the rate of the composite CV endpoint.;Secondary Objective: 1. To determine superiority of finerenone to placebo for each secondary endpoint.<br>2. To assess the safety and tolerability of finerenone.;Primary end point(s): The primary endpoint is the composite of Cardiovascular (CV) death and total (first and recurrent) HF<br>events (HHF or urgent HF visit) in HF patients (New York Heart Association [NYHA] class II–IV) and LVEF =40%.;Timepoint(s) of evaluation of this end point: Up to end of study.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Time to total (first and recurrent) HF events<br>2. Improvement in NYHA class from Baseline to Month 12<br>3. Change from baseline to Month 6, 9 and 12 in Total Symptom Score (TSS) from KCCQ.<br>4. Time to first occurrence of composite renal endpoint: sustained decrease in eGFR =50% relative to baseline over at least 4 weeks, or sustained eGFR decline <15ml/min/1.73m2 or initiation of dialysis or renal transplantation.<br>5. Time to all-cause mortality.;Timepoint(s) of evaluation of this end point: 1. Up to end of study (i.e. up to 42 months) <br>2. Up to 12 month after start of treatment.<br>3. Up to 12 month after start of treatment.<br>4. Up to end of study.<br>5. Up to end of study.

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