Efficacy and safety of finerenone in subjects with chronic heart failure at high risk of recurrent heart failure decompensation

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2015-002168-17-NL
• Date of registration: 30/09/2015
• Prospective Registration: Yes
• Primary sponsor: Bayer HealthCare AG
• Public title: Efficacy and safety of finerenone in subjects with chronic heart failure at high risk of recurrent heart failure decompensation
• Scientific title: A multicenter, randomized, double-blind, double-dummy, parallel-group, active-controlled study to evaluate the efficacy and safety of finerenone compared to eplerenone on morbidity and mortality in patients 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. - FINESSE-HF
• Date of first enrolment: 03/11/2015
• Target sample size: 5890
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002168-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: yes; Other trial design description: double-dummy; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: yes; Other specify the comparator: eplerenone; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

• Name: Bayer Clinical Trials Contact
• Affiliation: Bayer HealthCare AG

• Name: Bayer Clinical Trials Contact
• Affiliation: Bayer HealthCare AG

Key inclusion & exclusion criteria

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

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 1944
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3946

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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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
MedDRA version: 18.1 Level: LLT Classification code 10076410 Term: Chronic kidney disease stage 3 System Organ Class: 100000004857
MedDRA version: 18.1 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus System Organ Class: 100000004861
MedDRA version: 18.1 Level: LLT Classification code 10066498 Term: Cardiac failure chronic aggravated System Organ Class: 100000004849
MedDRA version: 18.1 Level: LLT Classification code 10076408 Term: Chronic kidney disease stage 1 System Organ Class: 100000004857
MedDRA version: 18.1 Level: LLT Classification code 10076409 Term: Chronic kidney disease stage 2 System Organ Class: 100000004857

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Product Name: BAY 94-8862 IR tablet 10 mg
Product Code: BAY 94-8862 coated tablet 10 mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Finerenone
CAS Number: 1050477-31-0
Current Sponsor code: BAY 94-8862 micronized
Other descriptive name: BAY 94-8862
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: BAY 94-8862 IR tablet 20 mg
Product Code: BAY 94-8862 coated tablet 20 mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Finerenone
CAS Number: 1050477-31-0
Current Sponsor code: BAY 94-8862 micronized
Other descriptive name: BAY 94-8862
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Eplerenone 25 mg Film-coated Tablets
Product Name: Eplerenone 25 mg Film-coated Tablets
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: EPLERENONE
CAS Number: 107724-20-9
Other descriptive name: EPLERENONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Eplerenone 50 mg Film-coated Tablets
Product Name: Ep

Primary Outcome(s)

Main Objective: 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).

Primary end point(s): Time to the first occurrence of the primary composite endpoint, consisting of the following components:
- CV death
- Hospitalization for HF

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

Secondary Objective: 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.

Secondary Outcome(s)

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

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

Secondary ID(s)

Results Statement

BAY94-8862/16275

2015-002168-17-SE

Source(s) of Monetary Support

Bayer HealthCare AG

Ethics review

Status: Approved
Approval date:
Contact: