Clinical trial NCT01807221: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure
Keywords: Heart Decompensation
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2013-03-08
Enrollment: 1066
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With a Relative Decrease in NT-proBNP of More Than 30% From Baseline to Day 90
timeFrame: Baseline and Day 90
Secondary outcomes:
measure: Number of Participants With Death Due to Any Cause
timeFrame: Day 30, Day 60, Day 90 and Follow-up (30 days post-last dose, assessed up to Day 120)
measure: Number of Participants With Cardiovascular Hospitalization
timeFrame: Day 30, Day 60, Day 90 and Follow-up (30 days post-last dose, assessed up to Day 120)
measure: Number of Participants With Emergency Presentations for Worsening Chronic Heart Failure (WCHF)
timeFrame: Day 30, Day 60, Day 90 and Follow-up (30 days post-last dose, assessed up to Day 120)
measure: Ratio of BNP at Specified Visits to BNP at Baseline
timeFrame: 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)
measure: Ratio of NT-proBNP at Specified Visits to NT-proBNP at Baseline
timeFrame: 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)
measure: Change From Baseline in KCCQ Questionnaire Scores at Specified Visits
timeFrame: Baseline, Day 30 and Day 90
measure: Change From Baseline in EQ-5D-3L Questionnaire Scores at Specified Visits
timeFrame: 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 outcomes:
measure: Change From Baseline in Serum Potassium at Specified Visits
timeFrame: Baseline, Day 30, Day 60, Day 90 and Follow-up (30 days post-last dose, assessed up to Day 120)
measure: Change From Baseline in Systolic Blood Pressure at Specified Visits
timeFrame: 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)
measure: Change From Baseline in Diastolic Blood Pressure at Specified Visits
timeFrame: 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)
measure: Change From Baseline in Heart Rate at Specified Visits
timeFrame: 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)
Locations:
city: Birmingham
country: United States
state: Alabama
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Jacksonville
country: United States
state: Florida
city: Macon
country: United States
state: Georgia
city: Baltimore
country: United States
state: Maryland
city: Detroit
country: United States
state: Michigan
city: Detroit
country: United States
state: Michigan
city: Newark
country: United States
state: New Jersey
city: Fairfield
country: United States
state: Ohio
city: Darlinghurst
country: Australia
state: New South Wales
city: Adelaide
country: Australia
state: South Australia
city: Concord
country: Australia
city: Prahran
country: Australia
city: Krems an der Donau
country: Austria
state: Niederösterreich
city: Linz
country: Austria
state: Oberösterreich
city: Graz
country: Austria
state: Steiermark
city: Graz
country: Austria
state: Steiermark
city: Innsbruck
country: Austria
state: Tirol
city: Salzburg
country: Austria
city: Wien
country: Austria
city: Burgas
country: Bulgaria
city: Pazardzhik
country: Bulgaria
city: Ruse
country: Bulgaria
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Varna
country: Bulgaria
city: Calgary
country: Canada
state: Alberta
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Saint-Jean-sur-Richelieu
country: Canada
state: Quebec
city: Sherbrooke
country: Canada
state: Quebec
city: Quebec
country: Canada
city: Jindrichuv Hradec
country: Czechia
city: Ostrava
country: Czechia
city: Praha 5
country: Czechia
city: Slany
country: Czechia
city: Copenhagen Ø
country: Denmark
city: Esbjerg
country: Denmark
city: Glostrup
country: Denmark
city: Hellerup
country: Denmark
city: Herlev
country: Denmark
city: Hvidovre
country: Denmark
city: København NV
country: Denmark
city: Køge
country: Denmark
city: Svendborg
country: Denmark
city: Viborg
country: Denmark
city: Espoo
country: Finland
city: Helsinki
country: Finland
city: Rovaniemi
country: Finland
city: Turku
country: Finland
city: Bron
country: France
city: Nice
country: France
city: PARIS cedex 10
country: France
city: Paris cedex 13
country: France
city: Rouen
country: France
city: Toulouse
country: France
city: Vandoeuvre les Nancy
country: France
city: Würzburg
country: Germany
state: Bayern
city: Frankfurt
country: Germany
state: Hessen
city: Limburg
country: Germany
state: Hessen
city: Göttingen
country: Germany
state: Niedersachsen
city: Hannover
country: Germany
state: Niedersachsen
city: Stade
country: Germany
state: Niedersachsen
city: Bad Oeynhausen
country: Germany
state: Nordrhein-Westfalen
city: Mönchengladbach
country: Germany
state: Nordrhein-Westfalen
city: Homburg
country: Germany
state: Saarland
city: Erfurt
country: Germany
state: Thüringen
city: Berlin
country: Germany
city: Athens
country: Greece
city: Athens
country: Greece
city: Chaidari
country: Greece
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country: Greece
city: Nea Ionia / Athens
country: Greece
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Nagykanizsa
country: Hungary
city: Szekesfehervar
country: Hungary
city: Afula
country: Israel
city: Ashkelon
country: Israel
city: Hadera
country: Israel
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Kfar Saba
country: Israel
city: Nahariya
country: Israel
city: Petach Tikva
country: Israel
city: Rehovot
country: Israel
city: Tel Aviv
country: Israel
city: Zefat
country: Israel
city: Zerifin
country: Israel
city: Roma
country: Italy
state: Lazio
city: Bergamo
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Monza Brianza
country: Italy
state: Lombardia
city: Foggia
country: Italy
state: Puglia
city: Arezzo
country: Italy
state: Toscana
city: Pisa
country: Italy
state: Toscana
city: Perugia
country: Italy
state: Umbria
city: Wonju
country: Korea, Republic of
state: Gang''weondo
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Kaunas
country: Lithuania
city: Kaunas
country: Lithuania
city: Kaunas
country: Lithuania
city: Klaipeda
country: Lithuania
city: Klaipeda
country: Lithuania
city: Vilnius
country: Lithuania
city: Amsterdam
country: Netherlands
city: Delft
country: Netherlands
city: Groningen
country: Netherlands
city: Groningen
country: Netherlands
city: Hoogeveen
country: Netherlands
city: Nijmegen
country: Netherlands
city: Rotterdam
country: Netherlands
city: Veldhoven
country: Netherlands
city: Zutphen
country: Netherlands
city: Stavanger
country: Norway
city: Bialystok
country: Poland
city: Bydgoszcz
country: Poland
city: Gdansk
country: Poland
city: Katowice
country: Poland
city: Kielce
country: Poland
city: Krakow
country: Poland
city: Szczecin
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Almada
country: Portugal
city: Faro
country: Portugal
city: Lisboa
country: Portugal
city: Lisboa
country: Portugal
city: Lisboa
country: Portugal
city: Porto
country: Portugal
city: Petoria
country: South Africa
state: Gauteng
city: Isipingo Rail
country: South Africa
state: Kwazulu-Natal
city: Merebank
country: South Africa
state: Kwazulu-Natal
city: Tongaat
country: South Africa
state: Kwazulu-Natal
city: Cape Town
country: South Africa
state: Western Cape
city: Kuils River
country: South Africa
state: Western Cape
city: Pinelands
country: South Africa
state: Western Cape
city: Somerset West
country: South Africa
state: Western Cape
city: Worcester
country: South Africa
state: Western Cape
city: Olot
country: Spain
state: Girona
city: Majadahonda
country: Spain
state: Madrid
city: El Palmar
country: Spain
state: Murcia
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Valencia
country: Spain
city: Valencia
country: Spain
city: Falun
country: Sweden
city: Göteborg
country: Sweden
city: Stockholm
country: Sweden
city: Stockholm
country: Sweden
city: Stockholm
country: Sweden
city: Umeå
country: Sweden
city: Örebro
country: Sweden
city: New Taipei City
country: Taiwan
city: Taipei
country: Taiwan
city: Taipei
country: Taiwan
city: Taipei
country: Taiwan
city: Taizung
country: Taiwan
city: Ankara
country: Turkey
city: Ankara
country: Turkey
city: Ankara
country: Turkey
city: Antalya
country: Turkey
city: Izmir
country: Turkey
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.