A Trial to Study BAY1753011 in Patients With Congestive Heart Failure

NCT03901729 | Completed Phase 2 DMC

• 2 other identifiers: 179092018-004059-18
• Study Type: interventional
• Target: 482
• Locations: 9 countries
• Sites: 66

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.

Conditions

Heart Failure (HF)

Keywords

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)

Outcome Measures

Primary Outcomes (4)

• PART A: Change in body weight

  Compare Day 30 (End of part A) with Day 1 (Start of part A)

• PART A: Change in serum creatinine

  Compare Day 30 (End of part A) with Day 1 (Start of part A)

• PART B: Change in body weight

  Compare Day 60 (End of part B) with Day 30 (Start of part B)

• PART B: Change in log transformed blood urea nitrogen (BUN)/creatinine ratio

  Compare Day 60 (End of part B) with Day 30 (Start of part B)

Secondary Outcomes (2)

• 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 index

  Up to 60 days

Study Arms (6)

Arm 1

EXPERIMENTAL

BAY1753011 30mg in addition to standard of care (SoC) for part A and part B

Drug: BAY 1753011

Arm 2

PLACEBO COMPARATOR

Placebo of BAY1753011 in addition to SoC for part A and part B

Other: Placebo BAY 1753011

Arm 1-A

EXPERIMENTAL

BAY1753011 30mg in addition to Placebo Furosemide 80mg for part B

Drug: BAY 1753011; Other: Placebo Furosemide

Arm 1-B

ACTIVE COMPARATOR

Furosemide 80mg in addition to Placebo BAY1753011 30mg for part B

Other: Placebo BAY 1753011; Drug: Furosemide

Arm 2-A

EXPERIMENTAL

BAY1753011 30mg in addition to Placebo Furosemide 80mg for part B

Drug: BAY 1753011; Other: Placebo Furosemide

Arm 2-B

ACTIVE COMPARATOR

Furosemide 80mg in addition to Placebo BAY1753011 30mg for part B

Other: Placebo BAY 1753011; Drug: Furosemide

Interventions

BAY 1753011 DRUG

Tablet; 30mg or 5mg unit; 30mg once daily in the morning; Oral

Arm 1; Arm 1-A; Arm 2-A

Placebo BAY 1753011 OTHER

Tablet; Once daily in the morning; Oral

Arm 1-B; Arm 2; Arm 2-B

Furosemide DRUG

Tablet; 40mg unit; 80mg once daily in the morning; Oral

Arm 1-B; Arm 2-B

Placebo Furosemide OTHER

Tablet; Once daily in the morning; Oral

Arm 1-A; Arm 2-A

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bayer: lead

Study Sites (66)

Universitätsklinikum St. Pölten

Sankt Pölten, Lower Austria, 3100, Austria

Location

Medizinische Universität Graz

Graz, Styria, 8036, Austria

Location

Krankenhaus St. Josef Braunau

Braunau am Inn, Upper Austria, 5280, Austria

Location

Universitätsklinikum AKH Wien

Vienna, 1090, Austria

Location

Klinik Floridsdorf - Krankenhaus Nord

Vienna, 1210, Austria

Location

MHAT Haskovo

Haskovo, 6300, Bulgaria

Location

Spec Hosp for Active Treatm in Cardiology Sv Georgi Pernik

Pernik, 2300, Bulgaria

Location

UMHAT Dr. Georgi Stranski

Pleven, 5800, Bulgaria

Location

Multiprofile Hospital for Active Treatment Medline Clinic

Plovdiv, 4000, Bulgaria

Location

MHAT "Knyaginya Klementina - Sofia"EAD

Sofia, 1233, Bulgaria

Location

NMTH Tzar Boris III

Sofia, 1233, Bulgaria

Location

UMHAT Tsaritsa Joanna-ISUL EAD Sofia

Sofia, 1527, Bulgaria

Location

KAT General Hospital of Athens

Kifisia / Athens, Attica, 14561, Greece

Location

G. GENNIMATAS General State Hospital of Athens

Athens, 11527, Greece

Location

University General Hospital of Athens "ATTIKON"

Chaidari - Athens, 12462, Greece

Location

University General Hospital of Ioannina

Ioannina, 45500, Greece

Location

Univ. General Hospital of Larissa

Larissa, 41100, Greece

Location

Konstantopoulio General Hospital of Nea Ionia - AGIA OLGA

Nea Ionia / Athens, 142 33, Greece

Location

"AHEPA" University General Hospital of Thessaloniki

Thessaloniki, 54636, Greece

Location

Hippokration General Hospital of Thessaloniki

Thessaloniki, 54642, Greece

Location

Budai Irgalmasrendi Korhaz

Budapest, 1023, Hungary

Location

University of Semmelweis/ Semmelweis Egyetem

Budapest, 1122, Hungary

Location

Magyar Honvedseg Egeszsegugyi Kozpont Honvedkorhaz

Budapest, Hungary

Location

Kanizsai Dorottya Hospital

Nagykanizsa, 8800, Hungary

Location

Josa Andras Hospital

Nyíregyháza, H-4400, Hungary

Location

Tolna Megyei Balassa Janos Korhaz

Szekszárd, 7100, Hungary

Location

Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz

Székesfehérvár, 8000, Hungary

Location

Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz

Szolnok, 5000, Hungary

Location

Zala Megyei Szent Rafael Korhaz

Zalaegerszeg, 8900, Hungary

Location

Barzilai Medical Center

Ashkelon, 7830604, Israel

Location

Rambam Health Corporation

Haifa, 3109601, Israel

Location

Hadassah Hebrew University Hospital Ein Kerem

Jerusalem, 9112001, Israel

Location

Health Corporation of Galilee Medical Center

Nahariya, 22100, Israel

Location

Chaim Sheba Medical Center

Ramat Gan, 5262000, Israel

Location

Tel-Aviv Sourasky Medical Center

Tel Aviv, 6423906, Israel

Location

Shamir Medical Center (Assaf Harofeh)

Zrifin, 7030000, Israel

Location

A.O.U. di Ferrara

Ferrara, Emilia-Romagna, 44124, Italy

Location

AUSL della Romagna

Rimini, Emilia-Romagna, 47923, Italy

Location

ASST Papa Giovanni XXIII

Bergamo, Lombardy, 24127, Italy

Location

ASST Spedali Civili di Brescia

Brescia, Lombardy, 25123, Italy

Location

IRCCS Centro Cardiologico Monzino S.p.A

Milan, Lombardy, 20138, Italy

Location

Fondazione Policlinico di Monza

Monza Brianza, Lombardy, 20900, Italy

Location

AUSL Toscana Sud-Est

Arezzo, Tuscany, 52044, Italy

Location

Fondazione Toscana Gabriele Monasterio (FTGM)

Pisa, Tuscany, 56124, Italy

Location

A.O.U. Senese

Siena, Tuscany, 53100, Italy

Location

Uniwersytecki Szpital Kliniczny w Bialymstoku

Bialystok, 15-276, Poland

Location

10 Wojskowy Szpital Kliniczny z Poliklinika SPZOZ

Bydgoszcz, 85-681, Poland

Location

Szpital sw. Wincentego a Paulo

Gdynia, 81-348, Poland

Location

Samodzielny Publiczny Specjalistyczny Szpital Zachodni

Grodzisk Mazowiecki, 05-825, Poland

Location

Szpital Kliniczny Przemienienia Panskiego

Poznan, 61-848, Poland

Location

Szpital Wojewodzki Nr 2

Rzeszów, 35-301, Poland

Location

Uniwersyteckie Centrum Kliniczne Warszawskiego UM

Warsaw, 02-097, Poland

Location

Uniwersytecki Szpital Kliniczny UM we Wroclawiu

Wroclaw, 50-556, Poland

Location

Hospital de Cascais

Alcabideche, Lisbon District, 2755-009, Portugal

Location

CHS - Hospital Sao Bernardo

Setúbal, Setúbal District, 2900-446, Portugal

Location

CHL - Hospital Santo Andre

Leiria, 2410-197, Portugal

Location

CHLO - Hospital Sao Francisco Xavier

Lisbon, 1449-005, Portugal

Location

Hospital da Luz - Lisboa

Lisbon, 1500-650, Portugal

Location

CHUP - Hospital Santo Antonio

Porto, 4099-001, Portugal

Location

Hospital Álvaro Cunqueiro

Babio - Beade, Pontevedra, 36312, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

Hospital General Universitario de Valencia

Valencia, 46014, Spain

Location

Hospital Universitari i Politècnic La Fe

Valencia, 46026, Spain

Location

Related Publications (3)

• Udelson JE, Goldsmith SR, Burkhoff D, Colorado P, Dinh W, Gustafsson F, Kolkhof P, Staedtler G, Bachmakov I, Voors AA, Duarte K, Monzo L, Girerd N, Zannad F. A multicentre, randomized, double-blind, active and placebo-controlled study of pecavaptan, a dual V1a/V2 vasopressin receptor antagonist, in patients with acute heart failure: The AVANTI trial. Eur J Heart Fail. 2025 Nov;27(11):2525-2536. doi: 10.1002/ejhf.3801. Epub 2025 Aug 11.

  PMID: 40788619 DERIVED

• Kazory A. Combination Diuretic Therapy to Counter Renal Sodium Avidity in Acute Heart Failure: Trials and Tribulations. Clin J Am Soc Nephrol. 2023 Oct 1;18(10):1372-1381. doi: 10.2215/CJN.0000000000000188. Epub 2023 Apr 27.

  PMID: 37102974 DERIVED

• Goldsmith SR, Burkhoff D, Gustafsson F, Voors A, Zannad F, Kolkhof P, Staedtler G, Colorado P, Dinh W, Udelson JE. Dual Vasopressin Receptor Antagonism to Improve Congestion in Patients With Acute Heart Failure: Design of the AVANTI Trial. J Card Fail. 2021 Feb;27(2):233-241. doi: 10.1016/j.cardfail.2020.10.007. Epub 2020 Oct 24.

  PMID: 33188886 DERIVED

Related Links

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

MeSH Terms

Conditions

Heart Failure

Interventions

Furosemide

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Sulfanilamides; Sulfonamides; Amides; Organic Chemicals; Aniline Compounds; Amines; Sulfones; Sulfur Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2019
• First Posted: April 3, 2019
• Study Start: May 29, 2019
• Primary Completion: April 16, 2021
• Study Completion: May 21, 2021
• Last Updated: April 18, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

PT (6); GR (8); AU (5); IL (7); PL (8); BU (7); HU (9); IT (9); ES (7)