E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with chronic heart failure and reduced ejection fraction after recent heart failure decompensation and additional risk factors, either type 2 diabetes mellitus or chronic kidney disease or both |
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E.1.1.1 | Medical condition in easily understood language |
CHF (reduction of the pumping capacity of the heart), DM type 2 (body's ineffective use of insulin) and CKD (kidneys fail to adequately filter toxins and waste products from the blood) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10076410 |
E.1.2 | Term | Chronic kidney disease stage 3 |
E.1.2 | System Organ Class | 100000004857 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II diabetes mellitus |
E.1.2 | System Organ Class | 100000004861 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066498 |
E.1.2 | Term | Cardiac failure chronic aggravated |
E.1.2 | System Organ Class | 100000004849 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10076408 |
E.1.2 | Term | Chronic kidney disease stage 1 |
E.1.2 | System Organ Class | 100000004857 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10076409 |
E.1.2 | Term | Chronic kidney disease stage 2 |
E.1.2 | System Organ Class | 100000004857 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Demonstrate the superiority of finerenone to eplerenone in delaying time to first occurrence of the composite endpoint, defined as cardiovascular (CV) death or hospitalization for heart failure (HF), in patients with chronic heart failure (CHF) (NYHA class II–IV) and reduced ejection fraction after recent heart failure decompensation who have additional risk factors, i.e. type 2 diabetes mellitus (T2DM) and/or or chronic kidney disease (CKD). |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to determine the superiority of finerenone to eplerenone with regard to the following: • Total number of hospitalizations (or equivalent) for HF • Time to first hospitalization (or equivalent) for HF • All-cause mortality • Time to first occurrence of composite renal endpoint: onset of kidney failure, or sustained decrease in estimated glomerular filtration rate (eGFR) ≥40% relative to baseline over at least 4 weeks, or renal death.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• 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. Adequate contraception is defined as any combination of at least 2 effective methods of birth control, of which at least one is a physical barrier (e.g. condoms with hormonal contraception or implants or combined oral contraceptives, certain intrauterine devices). Women are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels >40 mIU/mL [for US only: and estradiol <20 pg/mL] or have had surgical treatment such as bilateral tubal ligation, bilateral ovariectomy, or hysterectomy. • Diagnosis of CHF, NYHA class II-IV, and documented ejection fraction of ≤40% • Unscheduled emergency presentation to emergency services (outpatient or hospital, including the emergency department ) due to signs and/or symptoms of HF decompensation in the 2 weeks preceding randomization (considered as index event) • Administration of intravenous (IV) decongestive therapy at any time during presentation and/or admission to emergency services for the treatment of the index event • BNP >400 pg/mL or NT-proBNP >1200 pg/mL in sinus rhythm, and BNP >600 pg/mL or NT-proBNP >1800 pg/mL in atrial fibrillation, at any time starting with the index event, at the latest at screening; ; BNP values are not applicable for subjects taking angiotensin receptor-neprilysin inhibitors (ARNIs) • Type 2 diabetes mellitus (T2DM) in their medical history or at screening and/or Chronic kidney disease (CKD) with moderately reduced kidney function, defined as an estimated glomerular filtration rate (eGFR) between 30 and 60 mL/min/1.73 m² at screening (calculated using the locally approved and validated equation); one reassessment allowed
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E.4 | Principal exclusion criteria |
• Acute de-novo heart failure or acute inflammatory heart disease, e.g. acute myocarditis, within 3 months prior to randomization • Acute coronary syndrome, including unstable angina, non-ST segment elevation myocardial infarction (NSTEMI) or ST segment elevation myocardial infarction (STEMI), or major CV surgery including coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), implantation of a cardiac resynchronization therapy(CRT) device or cardiac contractility modulation (CCM) device, or carotid angioplasty within 3 months prior to randomization • Stroke or transient ischemic cerebral attack within 3 months prior to randomization • Cardiogenic shock at randomization, prior to first intake of study drug • Any primary cause of HF scheduled for surgery , e.g. valve disease such as severe aortic stenosis • History of heart transplant or need for heart transplantation; presence or need of left ventricular assist device
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to the first occurrence of the primary composite endpoint, consisting of the following components: - CV death - Hospitalization for HF |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From randomization (Visit 1) until the end of study following the study termination decision, approximately from 18 to 36 months |
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E.5.2 | Secondary end point(s) |
Secondary efficacy variables will be as follows: • Total number of hospitalizations (or equivalent) for HF •Time to first hospitalization (or equivalent) for HF •Time to all-cause mortality •Time to first occurrence of composite renal endpoint: o Onset of kidney failure o Sustained decrease in eGFR ≥40% relative to baseline over at least 4 weeks o Renal death |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From randomization (Visit 1) until the end of study following the study termination decision, approximately from 18 to 36 months |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 13 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 250 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Bulgaria |
Canada |
Chile |
China |
Colombia |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Greece |
Hong Kong |
Hungary |
Ireland |
Israel |
Italy |
Japan |
Korea, Republic of |
Lithuania |
Mexico |
Netherlands |
New Zealand |
Norway |
Poland |
Portugal |
Russian Federation |
Saudi Arabia |
Singapore |
South Africa |
Spain |
Sweden |
Switzerland |
Taiwan |
Turkey |
United Kingdom |
United States |
Vietnam |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 36 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 36 |