Phase IIb Safety and Efficacy Study of Different Oral Doses of BAY94-8862 in Subjects With Worsening Chronic Heart Failure and Left Ventricular Systolic Dysfunction and Either Type 2 Diabetes Mellitus With or Without Chronic Kidney Disease or Chronic Kidney Disease Alone (ARTS-HF)

A Randomized, Double-blind, Double-dummy, Multi-center Study to Assess Safety and Efficacy of Different Oral Doses of BAY94-8862 in Subjects With Emergency Presentation at the Hospital Because of Worsening Chronic Heart Failure With Left Ventricular Systolic Dysfunction and Either Type 2 Diabetes Mellitus With or Without Chronic Kidney Disease or Chronic Kidney Disease Alone Versus Eplerenone

To assess a new drug, BAY94-8862, given orally at different doses, to evaluate whether it was safe and can help the well-being of patients with worsening chronic heart failure and either type II diabetes with or without chronic kidney disease or kidney disease alone. These treatment doses were compared to eplerenone, another marketed drug approved to treat heart failure.

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Drug: Placebo; Drug: Inspra (eplerenone); Drug: Finerenone (BAY94-8862)

• Study Type: Interventional
• Enrollment (Actual): 1066
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Concord, Australia, 2139
  • Prahran, Australia, 3004
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
  • South Australia
    • Adelaide, South Australia, Australia, 5042
• Austria
  • Salzburg, Austria, 5020
  • Wien, Austria, 1100
  • Niederösterreich
    • Krems an der Donau, Niederösterreich, Austria, 3500
  • Oberösterreich
    • Linz, Oberösterreich, Austria, 4010
  • Steiermark
    • Graz, Steiermark, Austria, 8036
    • Graz, Steiermark, Austria, 8020
  • Tirol
    • Innsbruck, Tirol, Austria, 6020
• Bulgaria
  • Burgas, Bulgaria, 8018
  • Pazardzhik, Bulgaria, 4400
  • Ruse, Bulgaria, 7002
  • Sofia, Bulgaria, 1233
  • Sofia, Bulgaria, 1431
  • Sofia, Bulgaria, 1309
  • Varna, Bulgaria, 9010
• Canada
  • Quebec, Canada, G1V 4G5
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
  • Ontario
    • Ottawa, Ontario, Canada, K1Y 4W7
    • Toronto, Ontario, Canada, M5B 1W8
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
    • Montreal, Quebec, Canada, H1T 1C8
    • Montreal, Quebec, Canada, H2W 1T8
    • Saint-Jean-sur-Richelieu, Quebec, Canada, J3A 1C3
    • Sherbrooke, Quebec, Canada, J1H 5N4
• Czechia
  • Jindrichuv Hradec, Czechia, 377 01
  • Ostrava, Czechia, 728 80
  • Praha 5, Czechia, 150 30
  • Slany, Czechia, 274 01
• Denmark
  • Copenhagen Ø, Denmark, 2100
  • Esbjerg, Denmark, 6700
  • Glostrup, Denmark, 2600
  • Hellerup, Denmark, 2900
  • Herlev, Denmark, 2730
  • Hvidovre, Denmark, 2650
  • København NV, Denmark, 2400
  • Køge, Denmark, 4600
  • Svendborg, Denmark, 5700
  • Viborg, Denmark, 8800
• Finland
  • Espoo, Finland, 02740
  • Helsinki, Finland, 00099
  • Rovaniemi, Finland, 96101
  • Turku, Finland, 20520
• France
  • Bron, France, 69677
  • Nice, France, 06200
  • PARIS cedex 10, France, 75475
  • Paris cedex 13, France, 75013
  • Rouen, France, 76031
  • Toulouse, France, 31403
  • Vandoeuvre les Nancy, France, 54500
• Germany
  • Berlin, Germany, 13353
  • Bayern
    • Würzburg, Bayern, Germany, 97078
  • Hessen
    • Frankfurt, Hessen, Germany, 60389
    • Limburg, Hessen, Germany, 65549
  • Niedersachsen
    • Göttingen, Niedersachsen, Germany, 37099
    • Hannover, Niedersachsen, Germany, 30625
    • Stade, Niedersachsen, Germany, 21682
  • Nordrhein-Westfalen
    • Bad Oeynhausen, Nordrhein-Westfalen, Germany, 32545
    • Mönchengladbach, Nordrhein-Westfalen, Germany, 41063
  • Saarland
    • Homburg, Saarland, Germany, 66421
  • Thüringen
    • Erfurt, Thüringen, Germany, 99089
• Greece
  • Athens, Greece, 11527
  • Athens, Greece, 11526
  • Chaidari, Greece, 12462
  • Larissa, Greece, 41100
  • Nea Ionia / Athens, Greece, 14233
• Hungary
  • Budapest, Hungary, 1085
  • Budapest, Hungary, 1097
  • Budapest, Hungary, 1027
  • Nagykanizsa, Hungary, 8800
  • Szekesfehervar, Hungary, 8000
• Israel
  • Afula, Israel, 1834111
  • Ashkelon, Israel, 7830604
  • Hadera, Israel, 3810101
  • Haifa, Israel, 3436212
  • Jerusalem, Israel, 9103102
  • Kfar Saba, Israel, 4428164
  • Nahariya, Israel, 2210001
  • Petach Tikva, Israel, 4941492
  • Rehovot, Israel, 7610001
  • Tel Aviv, Israel, 64239
  • Zefat, Israel, 1311001
  • Zerifin, Israel, 7030000
• Italy
  • Lazio
    • Roma, Lazio, Italy, 00163
  • Lombardia
    • Bergamo, Lombardia, Italy, 24127
    • Milano, Lombardia, Italy, 20149
    • Monza Brianza, Lombardia, Italy, 20900
  • Puglia
    • Foggia, Puglia, Italy, 71100
  • Toscana
    • Arezzo, Toscana, Italy, 52040
    • Pisa, Toscana, Italy, 56124
  • Umbria
    • Perugia, Umbria, Italy, 06129
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
  • Seoul, Korea, Republic of, 05505
  • Seoul, Korea, Republic of, 03722
  • Gang''weondo
    • Wonju, Gang''weondo, Korea, Republic of, 26426
• Lithuania
  • Kaunas, Lithuania, LT-50161
  • Kaunas, Lithuania, LT-47144
  • Kaunas, Lithuania, LT-44320
  • Klaipeda, Lithuania, 92288
  • Klaipeda, Lithuania, LT-92288
  • Vilnius, Lithuania, LT-08661
• Netherlands
  • Amsterdam, Netherlands, 1061 AE
  • Delft, Netherlands, 2625 AD
  • Groningen, Netherlands, 9700 RB
  • Groningen, Netherlands, 9728 NT
  • Hoogeveen, Netherlands, 7909 AA
  • Nijmegen, Netherlands, 6525 GA
  • Rotterdam, Netherlands, 3045 PM
  • Veldhoven, Netherlands, 5504 DB
  • Zutphen, Netherlands, 7207 AE
• Norway
  • Stavanger, Norway, 4011
• Poland
  • Bialystok, Poland, 15-276
  • Bydgoszcz, Poland, 85-681
  • Gdansk, Poland, 80-952
  • Katowice, Poland, 40-635
  • Kielce, Poland, 25-736
  • Krakow, Poland, 31-121
  • Szczecin, Poland, 70-965
  • Warszawa, Poland, 04-628
  • Wroclaw, Poland, 50-981
• Portugal
  • Almada, Portugal, 2801-951
  • Faro, Portugal, 8000-386
  • Lisboa, Portugal, 1649-035
  • Lisboa, Portugal, 1449-005
  • Lisboa, Portugal, 1500-650
  • Porto, Portugal, P-4200
• South Africa
  • Gauteng
    • Petoria, Gauteng, South Africa
  • Kwazulu-Natal
    • Isipingo Rail, Kwazulu-Natal, South Africa, 4110
    • Merebank, Kwazulu-Natal, South Africa, 4052
    • Tongaat, Kwazulu-Natal, South Africa, 4400
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7500
    • Kuils River, Western Cape, South Africa, 7580
    • Pinelands, Western Cape, South Africa, 7405
    • Somerset West, Western Cape, South Africa, 7130
    • Worcester, Western Cape, South Africa, 6850
• Spain
  • Barcelona, Spain, 08003
  • Barcelona, Spain, 08035
  • Madrid, Spain, 28041
  • Valencia, Spain, 46026
  • Valencia, Spain, 46010
  • Girona
    • Olot, Girona, Spain, 17800
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
  • Murcia
    • El Palmar, Murcia, Spain, 30120
• Sweden
  • Falun, Sweden, 791 82
  • Göteborg, Sweden, 416 85
  • Stockholm, Sweden, 141 86
  • Stockholm, Sweden, 182 88
  • Stockholm, Sweden, 118 83
  • Umeå, Sweden, 901 85
  • Örebro, Sweden, 701 85
• Taiwan
  • New Taipei City, Taiwan, 220
  • Taipei, Taiwan
  • Taipei, Taiwan, 11217
  • Taipei, Taiwan, 10002
  • Taizung, Taiwan, 402
• Turkey
  • Ankara, Turkey
  • Ankara, Turkey, 06100
  • Ankara, Turkey, 06500
  • Antalya, Turkey, 07003
  • Izmir, Turkey, 35100
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-2041
  • California
    • La Jolla, California, United States, 92037
    • Los Angeles, California, United States, 90033
  • Florida
    • Jacksonville, Florida, United States, 32209
  • Georgia
    • Macon, Georgia, United States, 31201
  • Maryland
    • Baltimore, Maryland, United States, 21201
  • Michigan
    • Detroit, Michigan, United States, 48201
    • Detroit, Michigan, United States, 48202
  • New Jersey
    • Newark, New Jersey, United States, 07103
  • Ohio
    • Fairfield, Ohio, United States, 45014

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women aged 18 years and older. The lower age limit may be higher if legally required in the participating country
• Women of childbearing potential can only be included in the study if a pregnancy test is negative and if they agree to use adequate contraception when sexually active
• Subjects with worsening chronic heart failure requiring emergency presentation to hospital and treatment with intravenous diuretics at hospital
• Subjects with clinical diagnosis of chronic heart failure (CHF) either ischemic or non ischemic, New York Heart Association (NYHA) functional class II-IV
• Subjects with type 2 diabetes mellitus and / or
• Subjects with 30 mL/min/1.73m^2 </= eGFR </= 60 mL/min/1.73m^2 (MDRD, Modification of Diet in Renal Disease Study Group) at screening
• Left ventricular ejection fraction (LVEF) </= 40%
• Blood potassium </= 5.0 mmol/L at screening
• Systolic blood pressure >/= 90 mmHg without signs and symptoms of hypotension at the screening visit

Exclusion Criteria:

• Acute de-novo heart failure or acute inflammatory heart disease, e.g. acute myocarditis
• Acute coronary syndrome (ACS) in last 30 days prior to screening
• Cardiogenic shock
• Valvular heart disease requiring surgical intervention during the course of the study
• Stroke or transient ischemic cerebral attack in the last 3 months prior to the screening visit
• Concomitant treatment with any mineralocorticoid receptor antagonist (MRA), renin inhibitor, or potassium-sparing diuretic

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Finerenone(BAY94-8862)[2.5mg] + Placebo; Oral - 2.5mg once daily (OD) for 30 days. Potential up-titration to 5mg OD after 30 days or 60 days. Treatment duration 90 days. Placebo OD for 90 days.	Drug: Placebo; Drug: Finerenone (BAY94-8862)
EXPERIMENTAL: Finerenone (BAY94-8862)[5mg] + Placebo; Oral - 5mg OD for 30 days. Potential up-titration to 10 mg OD after 30 days or 60 days. Treatment duration 90 days. Placebo OD for 90 days.	Drug: Placebo; Drug: Finerenone (BAY94-8862)
EXPERIMENTAL: Finerenone (BAY94-8862)[7.5mg] + Placebo; Oral - 7.5mg OD for 30 days. Potential up-titration to 15 mg OD after 30 days or 60 days. Treatment duration 90 days. Placebo OD for 90 days.	Drug: Placebo; Drug: Finerenone (BAY94-8862)
EXPERIMENTAL: Finerenone (BAY94-8862)[10mg] + Placebo; Oral - 10mg OD for 30 days. Potential up-titration to 20 mg OD after 30 days or 60 days. Treatment duration 90 days. Placebo OD for 90 days.	Drug: Placebo; Drug: Finerenone (BAY94-8862)
EXPERIMENTAL: Finerenone (BAY94-8862)[15mg] + Placebo; Oral - 15mg OD for 30 days. Potential up-titration to 20 mg OD after 30 days or 60 days. Treatment duration 90 days. Placebo OD for 90 days.	Drug: Placebo; Drug: Finerenone (BAY94-8862)
ACTIVE_COMPARATOR: Eplerenone [25 mg] + Placebo; Oral - 25mg every other day (EOD). Potential up-titration to 25mg OD after 30 days and 50mg OD after 60 days.Placebo OD for 90 days.	Drug: Placebo; Drug: Inspra (eplerenone)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a Relative Decrease in NT-proBNP of More Than 30% From Baseline to Day 90	N-terminal pro-B type natriuretic peptide (NT-proBNP) levels in the blood are used for screening, diagnosis of acute and chronic heart failure (CHF) and may be useful to establish prognosis in heart failure.	Baseline and Day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Death Due to Any Cause	Death due to any cause include cardiovascular (CV) death and Non-CV death. Non-CV death was classified by 2 subcategories: non-malignant causes and malignant causes.	Day 30, Day 60, Day 90 and Follow-up (30 days post-last dose, assessed up to Day 120)
Number of Participants With Cardiovascular Hospitalization	Hospitalizations were defined as any unplanned admission to hospital, i.e. completion of hospital admission procedures and one overnight [i.e. date change] stay or until the death of subject occurred. Hospitalizations and deaths were classified by 2 primary categories: CV and non-CV. The pre-specified subcategories for CV hospitalizations were as follows: 1. Worsening heart failure, 2.Acute myocardial infarction, 3. Arrhythmia, 4.Transient ischemic attack and stroke, 5. Other CV hospitalizations.	Day 30, Day 60, Day 90 and Follow-up (30 days post-last dose, assessed up to Day 120)
Number of Participants With Emergency Presentations for Worsening Chronic Heart Failure (WCHF)	Emergency presentations for WCHF were defined as newly developing signs and symptoms of WCHF after start of treatment with study drug, requiring an additional emergency presentation to hospital and IV treatment with diuretics and/or positive inotropic agents.	Day 30, Day 60, Day 90 and Follow-up (30 days post-last dose, assessed up to Day 120)
Ratio of BNP at Specified Visits to BNP at Baseline	B-type natriuretic peptide (BNP) levels in the blood are used for screening, diagnosis of acute chronic heart failure (CHF) and may be useful to establish prognosis in heart failure.	Day 30, Day 60, Day 90, Premature discontinuation (only for participants who have discontinued the study prematurely, to be performed as soon as possible after withdrawal of study drug) and Follow-up (30 days post-last dose, assessed up to Day 120)
Ratio of NT-proBNP at Specified Visits to NT-proBNP at Baseline	N-terminal pro-B type natriuretic peptide (NT-proBNP) levels in the blood are used for screening, diagnosis of acute chronic heart failure (CHF) and may be useful to establish prognosis in heart failure.	Day 30, Day 60, Day 90, Premature discontinuation (only for participants who have discontinued the study prematurely, to be performed as soon as possible after withdrawal of study drug) and Follow-up (30 days post-last dose, assessed up to Day 120)
Change From Baseline in KCCQ Questionnaire Scores at Specified Visits	The Kansas City Cardiomyopathy Questionnaire (KCCQ) was the leading health related quality of life measure for subjects with CHF. KCCQ was a 23 item questionnaire that independently measures the impact of subjects HF, or its treatment, on 7 distinct domains: self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. KCCQ clinical summary score is a composite assessment of physical limitations and total symptom scores. Results from the total symptom summary score are presented. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. In the below table, categorical data represents change from baseline data at respective time points.	Baseline, Day 30 and Day 90
Change From Baseline in EQ-5D-3L Questionnaire Scores at Specified Visits	EuroQol Group 5-Dimension, 3-Level (EQ-5D-3L): participant rated questionnaire to assess health-related quality of life. It consists of EQ-5D descriptive system and EQ-5D Visual Analog Scale (VAS). EQ-5D-3L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems (1), some problems (2), and extreme problems (3). For this population, the possible EQ-5D-3L index scores ranges from -0.11 (that is, 3 for all 5 dimensions) to 1.0 (that is, 1 for all 5 dimensions), where higher scores indicate a better health state.	Baseline, Day 30, Day 90, Premature discontinuation (only for participants who have discontinued the study prematurely, to be performed as soon as possible after withdrawal of study drug) and Follow-up (30 days post-last dose, assessed up to Day 120)

Other Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in Serum Potassium at Specified Visits	Baseline, Day 30, Day 60, Day 90 and Follow-up (30 days post-last dose, assessed up to Day 120)
Change From Baseline in Systolic Blood Pressure at Specified Visits	Baseline,Day 7,14,30,60,90,Premature discontinuation (only for participants who have discontinued the study prematurely, to be performed as soon as possible after withdrawal of study drug) and Follow-up (30 days post-last dose, assessed up to Day 120)
Change From Baseline in Diastolic Blood Pressure at Specified Visits	Baseline,Day 7,14,30,60,90,Premature discontinuation (only for participants who have discontinued the study prematurely, to be performed as soon as possible after withdrawal of study drug) and Follow-up (30 days post-last dose, assessed up to Day 120)
Change From Baseline in Heart Rate at Specified Visits	Baseline,Day 7,14,30,60,90,Premature discontinuation (only for participants who have discontinued the study prematurely, to be performed as soon as possible after withdrawal of study drug) and Follow-up (30 days post-last dose, assessed up to Day 120)

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• Chung EY, Ruospo M, Natale P, Bolignano D, Navaneethan SD, Palmer SC, Strippoli GF. Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2020 Oct 27;10(10):CD007004. doi: 10.1002/14651858.CD007004.pub4.
• Filippatos G, Anker SD, Bohm M, Gheorghiade M, Kober L, Krum H, Maggioni AP, Ponikowski P, Voors AA, Zannad F, Kim SY, Nowack C, Palombo G, Kolkhof P, Kimmeskamp-Kirschbaum N, Pieper A, Pitt B. A randomized controlled study of finerenone vs. eplerenone in patients with worsening chronic heart failure and diabetes mellitus and/or chronic kidney disease. Eur Heart J. 2016 Jul 14;37(27):2105-14. doi: 10.1093/eurheartj/ehw132. Epub 2016 Apr 29.
• Pitt B, Anker SD, Bohm M, Gheorghiade M, Kober L, Krum H, Maggioni AP, Ponikowski P, Voors AA, Zannad F, Nowack C, Kim SY, Pieper A, Kimmeskamp-Kirschbaum N, Filippatos G. Rationale and design of MinerAlocorticoid Receptor antagonist Tolerability Study-Heart Failure (ARTS-HF): a randomized study of finerenone vs. eplerenone in patients who have worsening chronic heart failure with diabetes and/or chronic kidney disease. Eur J Heart Fail. 2015 Feb;17(2):224-32. doi: 10.1002/ejhf.218.

Helpful Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe.
• Click here to find results for studies related to Bayer Healthcare products.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 17, 2013
• Primary Completion (ACTUAL): November 11, 2014
• Study Completion (ACTUAL): December 9, 2014

Study Registration Dates

• First Submitted: March 7, 2013
• First Submitted That Met QC Criteria: March 7, 2013
• First Posted (ESTIMATE): March 8, 2013

Study Record Updates

• Last Update Posted (ACTUAL): July 6, 2021
• Last Update Submitted That Met QC Criteria: July 2, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Heart Decompensation
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Urologic Diseases; Endocrine System Diseases; Renal Insufficiency; Heart Failure; Diabetes Mellitus; Diabetes Mellitus, Type 2; Kidney Diseases; Renal Insufficiency, Chronic; Physiological Effects of Drugs; Antihypertensive Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Eplerenone
• Other Study ID Numbers: 14564; 2012-002627-15 (EUDRACT_NUMBER)