A Trial to Study BAY1753011 in Patients With Congestive Heart Failure (AVANTI)
Heart Failure (HF)
About this trial
This is an interventional treatment trial for Heart Failure (HF) focused on measuring Chronic heart failure (CHF), Heart failure with reduced ejection fraction (HFrEF), Heart failure with preserved ejection fraction (HFpEF), Heart failure with mid-range ejection fraction (HFmrEF)
Eligibility Criteria
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.
Sites / Locations
- Universitätsklinikum St. Pölten
- Krankenhaus St. Josef Braunau
- Medizinische Universität Graz
- Universitätsklinikum AKH Wien
- Klinik Floridsdorf - Krankenhaus Nord
- MHAT Haskovo
- Spec Hosp for Active Treatm in Cardiology Sv Georgi Pernik
- UMHAT Dr. Georgi Stranski
- Multiprofile Hospital for Active Treatment Medline Clinic
- MHAT "Knyaginya Klementina - Sofia"EAD
- NMTH Tzar Boris III
- UMHAT Tsaritsa Joanna-ISUL EAD Sofia
- KAT General Hospital of Athens
- G. GENNIMATAS General State Hospital of Athens
- University General Hospital of Athens "ATTIKON"
- University General Hospital of Ioannina
- Univ. General Hospital of Larissa
- Konstantopoulio General Hospital of Nea Ionia - AGIA OLGA
- "AHEPA" University General Hospital of Thessaloniki
- Hippokration General Hospital of Thessaloniki
- Budai Irgalmasrendi Korhaz
- University of Semmelweis/ Semmelweis Egyetem
- Magyar Honvedseg Egeszsegugyi Kozpont Honvedkorhaz
- Kanizsai Dorottya Hospital
- Josa Andras Hospital
- Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
- Tolna Megyei Balassa Janos Korhaz
- Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz
- Zala Megyei Szent Rafael Korhaz
- Barzilai Medical Center
- Rambam Health Corporation
- Hadassah Hebrew University Hospital Ein Kerem
- Health Corporation of Galilee Medical Center
- Chaim Sheba Medical Center
- Tel-Aviv Sourasky Medical Center
- Shamir Medical Center (Assaf Harofeh)
- A.O.U. di Ferrara
- AUSL della Romagna
- ASST Papa Giovanni XXIII
- ASST Spedali Civili di Brescia
- IRCCS Centro Cardiologico Monzino S.p.A
- Fondazione Policlinico di Monza
- AUSL Toscana Sud-Est
- Fondazione Toscana Gabriele Monasterio (FTGM)
- A.O.U. Senese
- Uniwersytecki Szpital Kliniczny w Bialymstoku
- 10 Wojskowy Szpital Kliniczny z Poliklinika SPZOZ
- Szpital sw. Wincentego a Paulo
- Samodzielny Publiczny Specjalistyczny Szpital Zachodni
- Szpital Kliniczny Przemienienia Panskiego
- Szpital Wojewodzki Nr 2
- Uniwersyteckie Centrum Kliniczne Warszawskiego UM
- Uniwersytecki Szpital Kliniczny UM we Wroclawiu
- Hospital de Cascais
- CHS - Hospital Sao Bernardo
- CHL - Hospital Santo Andre
- CHLO - Hospital Sao Francisco Xavier
- Hospital da Luz - Lisboa
- CHUP - Hospital Santo Antonio
- Hospital Álvaro Cunqueiro
- Hospital del Mar
- Hospital Ramón y Cajal
- Hospital Virgen de la Victoria
- Hospital Clínico Universitario de Valencia
- Hospital General Universitario de Valencia
- Hospital Universitari i Politècnic La Fe
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Experimental
Placebo Comparator
Experimental
Active Comparator
Experimental
Active Comparator
Arm 1
Arm 2
Arm 1-A
Arm 1-B
Arm 2-A
Arm 2-B
BAY1753011 30mg in addition to standard of care (SoC) for part A and part B
Placebo of BAY1753011 in addition to SoC for part A and part B
BAY1753011 30mg in addition to Placebo Furosemide 80mg for part B
Furosemide 80mg in addition to Placebo BAY1753011 30mg for part B
BAY1753011 30mg in addition to Placebo Furosemide 80mg for part B
Furosemide 80mg in addition to Placebo BAY1753011 30mg for part B