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A Trial to Study BAY1753011 in Patients With Congestive Heart Failure

Phase 2
Completed
Conditions
Heart Failure (HF)
Interventions
Other: Placebo BAY 1753011
Drug: BAY 1753011
Other: Placebo Furosemide
Registration Number
NCT03901729
Lead Sponsor
Bayer
Brief Summary

To assess the efficacy of 30 mg of BAY1753011, with or without furosemide, versus furosemide alone in patients with heart failure and objective evidence of congestion.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
482
Inclusion Criteria
  • History of CHF on individually optimized treatment with HF medications unless contraindicated or not tolerated, for at least 12 weeks prior to index hospitalization and in accordance with international guidelines.

  • Subjects admitted to the hospital with a primary diagnosis of decompensated HF including symptoms and signs of fluid overload requiring IV diuretic therapy in the Emergency room (ER) or any time between day 1-3 of hospital admission (index hospitalization).

  • Subjects on an average/usual total daily dose of loop diuretic ≥ 40 mg of furosemide or equivalent, within 4 weeks prior to index hospitalization.

  • At least one of the following 5 parameters any day between 3-7 of index hospitalization (screening period)

    • Natriuretic peptides Brain natriuretic peptide/N-terminal prohormone of brain natriuretic peptide (BNP/NT-proBNP):

      • Drop in BNP or NT-proBNP ≤ 30% from admission values (if measured during index hospitalization) or
      • BNP ≥ 500 pg/ml or NT-proBNP ≥ 1800 pg/ml at screening (day 3 to 7 of index hospitalization)
    • Body weight (BW) loss <0.4 kg per 40 mg furosemide at day 4 of index hospitalization

    • Composite congestion score (CCS) ≥ 3

    • Hypervolemic hyponatremia defined as serum sodium < 136 mmol/l

    • In hospital worsening renal function defined as increased serum creatinine ≥ 0.3 mg/dl compared to index hospitalization admission values AND at least one the following

      • Jugular venous pressure (JVP) ≥ 10 cm on physical examination
      • Inferior vena cava (IVC) diameter > 21 mm
      • IVC collapse with sniff < 50%
      • At least 2+ peripheral edema or pulmonary edema or pleural effusion on chest X-ray or clinical exam

Exclusion Criteria

  • Active or history of acute inflammatory heart disease, within 3 months prior to screening, e.g., acute myocarditis
  • Acute coronary syndrome, including unstable angina, Non-ST segment elevation myocardial infarction (NSTEMI) or ST segment elevation myocardial infarction (STEMI), or major Cardiovascular (CV) surgery including coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI) within 3 months prior to screening
  • Any primary cause of HF scheduled for surgery or interventional therapy (e.g., TAVI), e.g., valve disease such as severe aortic stenosis or mitral valve regurgitation
  • Requirement of mechanical support (intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, or any ventricular assist device) or ultrafiltration/hemodialysis
  • Estimated glomerular filtration rate of < 30 ml/min/1.73 m*2 determined by the Modified Diet and Renal Disease equation at screening; reassessments allowed as clinically needed
  • Serum potassium ≥ 5.5 mmol/L or ≤ 3.3 mmol/L at screening; reassessments allowed as clinically needed
  • Serum sodium ≥ 146 mmol/L or ≤ 130 mmol/L at screening; reassessments allowed as clinically needed
  • Concomitant treatment with potassium-sparing diuretic (with the exception of mineralocorticoid- receptor antagonist (MRA) that cannot be stopped prior to randomization and for the duration of the treatment period.
Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm 2Placebo BAY 1753011Placebo of BAY1753011 in addition to SoC for part A and part B
Arm 2-BPlacebo BAY 1753011Furosemide 80mg in addition to Placebo BAY1753011 30mg for part B
Arm 1-APlacebo FurosemideBAY1753011 30mg in addition to Placebo Furosemide 80mg for part B
Arm 1-BPlacebo BAY 1753011Furosemide 80mg in addition to Placebo BAY1753011 30mg for part B
Arm 1BAY 1753011BAY1753011 30mg in addition to standard of care (SoC) for part A and part B
Arm 1-ABAY 1753011BAY1753011 30mg in addition to Placebo Furosemide 80mg for part B
Arm 2-ABAY 1753011BAY1753011 30mg in addition to Placebo Furosemide 80mg for part B
Arm 2-APlacebo FurosemideBAY1753011 30mg in addition to Placebo Furosemide 80mg for part B
Arm 1-BFurosemideFurosemide 80mg in addition to Placebo BAY1753011 30mg for part B
Arm 2-BFurosemideFurosemide 80mg in addition to Placebo BAY1753011 30mg for part B
Primary Outcome Measures
NameTimeMethod
PART A: Change in serum creatinineCompare Day 30 (End of part A) with Day 1 (Start of part A)
PART B: Change in body weightCompare Day 60 (End of part B) with Day 30 (Start of part B)
PART A: Change in body weightCompare Day 30 (End of part A) with Day 1 (Start of part A)
PART B: Change in log transformed blood urea nitrogen (BUN)/creatinine ratioCompare Day 60 (End of part B) with Day 30 (Start of part B)
Secondary Outcome Measures
NameTimeMethod
Incidence of Treatment-emergent adverse event (including Serious adverse event)From the time of first study drug administration up to 7 days after the last dose of study drug (Day 60)
Change in augmentation indexUp to 60 days

Trial Locations

Locations (66)

Universitätsklinikum St. Pölten

🇦🇹

St. Pölten, Niederösterreich, Austria

Medizinische Universität Graz

🇦🇹

Graz, Steiermark, Austria

Universitätsklinikum AKH Wien

🇦🇹

Wien, Austria

MHAT Haskovo

🇧🇬

Haskovo, Bulgaria

Spec Hosp for Active Treatm in Cardiology Sv Georgi Pernik

🇧🇬

Pernik, Bulgaria

Multiprofile Hospital for Active Treatment Medline Clinic

🇧🇬

Plovdiv, Bulgaria

UMHAT Dr. Georgi Stranski

🇧🇬

Pleven, Bulgaria

MHAT "Knyaginya Klementina - Sofia"EAD

🇧🇬

Sofia, Bulgaria

NMTH Tzar Boris III

🇧🇬

Sofia, Bulgaria

UMHAT Tsaritsa Joanna-ISUL EAD Sofia

🇧🇬

Sofia, Bulgaria

G. GENNIMATAS General State Hospital of Athens

🇬🇷

Athens, Greece

University General Hospital of Ioannina

🇬🇷

Ioannina, Greece

Univ. General Hospital of Larissa

🇬🇷

Larissa, Greece

"AHEPA" University General Hospital of Thessaloniki

🇬🇷

Thessaloniki, Greece

Budai Irgalmasrendi Korhaz

🇭🇺

Budapest, Hungary

University of Semmelweis/ Semmelweis Egyetem

🇭🇺

Budapest, Hungary

Kanizsai Dorottya Hospital

🇭🇺

Nagykanizsa, Hungary

Magyar Honvedseg Egeszsegugyi Kozpont Honvedkorhaz

🇭🇺

Budapest, Hungary

Tolna Megyei Balassa Janos Korhaz

🇭🇺

Szekszard, Hungary

Rambam Health Corporation

🇮🇱

Haifa, Israel

Health Corporation of Galilee Medical Center

🇮🇱

Nahariya, Israel

ASST Spedali Civili di Brescia

🇮🇹

Brescia, Lombardia, Italy

A.O.U. di Ferrara

🇮🇹

Ferrara, Emilia-Romagna, Italy

AUSL Toscana Sud-Est

🇮🇹

Arezzo, Toscana, Italy

A.O.U. Senese

🇮🇹

Siena, Toscana, Italy

10 Wojskowy Szpital Kliniczny z Poliklinika SPZOZ

🇵🇱

Bydgoszcz, Poland

Samodzielny Publiczny Specjalistyczny Szpital Zachodni

🇵🇱

Grodzisk Mazowiecki, Poland

Szpital Wojewodzki Nr 2

🇵🇱

Rzeszow, Poland

Uniwersyteckie Centrum Kliniczne Warszawskiego UM

🇵🇱

Warszawa, Poland

Uniwersytecki Szpital Kliniczny UM we Wroclawiu

🇵🇱

Wroclaw, Poland

Hospital de Cascais

🇵🇹

Alcabideche, Lisboa, Portugal

CHS - Hospital Sao Bernardo

🇵🇹

Setubal, Setúbal, Portugal

CHL - Hospital Santo Andre

🇵🇹

Leiria, Portugal

Hospital da Luz - Lisboa

🇵🇹

Lisboa, Portugal

CHUP - Hospital Santo Antonio

🇵🇹

Porto, Portugal

CHLO - Hospital Sao Francisco Xavier

🇵🇹

Lisboa, Portugal

Hospital Álvaro Cunqueiro

🇪🇸

Babio - Beade, Pontevedra, Spain

Hospital del Mar

🇪🇸

Barcelona, Spain

Hospital Ramón y Cajal

🇪🇸

Madrid, Spain

Hospital Clínico Universitario de Valencia

🇪🇸

Valencia, Spain

Hospital Virgen de la Victoria

🇪🇸

Málaga, Spain

Hospital General Universitario de Valencia

🇪🇸

Valencia, Spain

Hospital Universitari i Politècnic La Fe

🇪🇸

Valencia, Spain

University General Hospital of Athens "ATTIKON"

🇬🇷

Chaidari - Athens, Greece

ASST Papa Giovanni XXIII

🇮🇹

Bergamo, Lombardia, Italy

IRCCS Centro Cardiologico Monzino S.p.A

🇮🇹

Milano, Lombardia, Italy

Fondazione Policlinico di Monza

🇮🇹

Monza Brianza, Lombardia, Italy

Fondazione Toscana Gabriele Monasterio (FTGM)

🇮🇹

Pisa, Toscana, Italy

AUSL della Romagna

🇮🇹

Rimini, Emilia-Romagna, Italy

Zala Megyei Szent Rafael Korhaz

🇭🇺

Zalaegerszeg, Hungary

Shamir Medical Center (Assaf Harofeh)

🇮🇱

Zrifin, Israel

KAT General Hospital of Athens

🇬🇷

Kifisia / Athens, Attica, Greece

Tel-Aviv Sourasky Medical Center

🇮🇱

Tel Aviv, Israel

Uniwersytecki Szpital Kliniczny w Bialymstoku

🇵🇱

Bialystok, Poland

Szpital Kliniczny Przemienienia Panskiego

🇵🇱

Poznan, Poland

Krankenhaus St. Josef Braunau

🇦🇹

Braunau, Oberösterreich, Austria

Klinik Floridsdorf - Krankenhaus Nord

🇦🇹

Wien, Austria

Hippokration General Hospital of Thessaloniki

🇬🇷

Thessaloniki, Greece

Hadassah Hebrew University Hospital Ein Kerem

🇮🇱

Jerusalem, Israel

Konstantopoulio General Hospital of Nea Ionia - AGIA OLGA

🇬🇷

Nea Ionia / Athens, Greece

Josa Andras Hospital

🇭🇺

Nyiregyhaza, Hungary

Barzilai Medical Center

🇮🇱

Ashkelon, Israel

Chaim Sheba Medical Center

🇮🇱

Ramat Gan, Israel

Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz

🇭🇺

Szekesfehervar, Hungary

Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz

🇭🇺

Szolnok, Hungary

Szpital sw. Wincentego a Paulo

🇵🇱

Gdynia, Poland

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