A Trial to Study BAY1753011 in Patients With Congestive Heart Failure

NCT ID: NCT03901729

Last Updated: 2022-04-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

482 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-05-29

Study Completion Date

2021-05-21

Brief Summary

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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

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Conditions

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Heart Failure (HF)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Arm 1

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

Group Type EXPERIMENTAL

BAY 1753011

Intervention Type DRUG

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

Arm 2

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

Group Type PLACEBO_COMPARATOR

Placebo BAY 1753011

Intervention Type OTHER

Tablet; Once daily in the morning; Oral

Arm 1-A

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

Group Type EXPERIMENTAL

BAY 1753011

Intervention Type DRUG

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

Placebo Furosemide

Intervention Type OTHER

Tablet; Once daily in the morning; Oral

Arm 1-B

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

Group Type ACTIVE_COMPARATOR

Placebo BAY 1753011

Intervention Type OTHER

Tablet; Once daily in the morning; Oral

Furosemide

Intervention Type DRUG

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

Arm 2-A

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

Group Type EXPERIMENTAL

BAY 1753011

Intervention Type DRUG

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

Placebo Furosemide

Intervention Type OTHER

Tablet; Once daily in the morning; Oral

Arm 2-B

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

Group Type ACTIVE_COMPARATOR

Placebo BAY 1753011

Intervention Type OTHER

Tablet; Once daily in the morning; Oral

Furosemide

Intervention Type DRUG

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

Interventions

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BAY 1753011

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

Intervention Type DRUG

Placebo BAY 1753011

Tablet; Once daily in the morning; Oral

Intervention Type OTHER

Furosemide

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

Intervention Type DRUG

Placebo Furosemide

Tablet; Once daily in the morning; Oral

Intervention Type OTHER

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bayer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Universitätsklinikum St. Pölten

Sankt Pölten, Lower Austria, Austria

Site Status

Medizinische Universität Graz

Graz, Styria, Austria

Site Status

Krankenhaus St. Josef Braunau

Braunau am Inn, Upper Austria, Austria

Site Status

Universitätsklinikum AKH Wien

Vienna, , Austria

Site Status

Klinik Floridsdorf - Krankenhaus Nord

Vienna, , Austria

Site Status

MHAT Haskovo

Haskovo, , Bulgaria

Site Status

Spec Hosp for Active Treatm in Cardiology Sv Georgi Pernik

Pernik, , Bulgaria

Site Status

UMHAT Dr. Georgi Stranski

Pleven, , Bulgaria

Site Status

Multiprofile Hospital for Active Treatment Medline Clinic

Plovdiv, , Bulgaria

Site Status

MHAT "Knyaginya Klementina - Sofia"EAD

Sofia, , Bulgaria

Site Status

NMTH Tzar Boris III

Sofia, , Bulgaria

Site Status

UMHAT Tsaritsa Joanna-ISUL EAD Sofia

Sofia, , Bulgaria

Site Status

KAT General Hospital of Athens

Kifisia / Athens, Attica, Greece

Site Status

G. GENNIMATAS General State Hospital of Athens

Athens, , Greece

Site Status

University General Hospital of Athens "ATTIKON"

Chaidari - Athens, , Greece

Site Status

University General Hospital of Ioannina

Ioannina, , Greece

Site Status

Univ. General Hospital of Larissa

Larissa, , Greece

Site Status

Konstantopoulio General Hospital of Nea Ionia - AGIA OLGA

Nea Ionia / Athens, , Greece

Site Status

"AHEPA" University General Hospital of Thessaloniki

Thessaloniki, , Greece

Site Status

Hippokration General Hospital of Thessaloniki

Thessaloniki, , Greece

Site Status

Budai Irgalmasrendi Korhaz

Budapest, , Hungary

Site Status

University of Semmelweis/ Semmelweis Egyetem

Budapest, , Hungary

Site Status

Magyar Honvedseg Egeszsegugyi Kozpont Honvedkorhaz

Budapest, , Hungary

Site Status

Kanizsai Dorottya Hospital

Nagykanizsa, , Hungary

Site Status

Josa Andras Hospital

Nyíregyháza, , Hungary

Site Status

Tolna Megyei Balassa Janos Korhaz

Szekszárd, , Hungary

Site Status

Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz

Székesfehérvár, , Hungary

Site Status

Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz

Szolnok, , Hungary

Site Status

Zala Megyei Szent Rafael Korhaz

Zalaegerszeg, , Hungary

Site Status

Barzilai Medical Center

Ashkelon, , Israel

Site Status

Rambam Health Corporation

Haifa, , Israel

Site Status

Hadassah Hebrew University Hospital Ein Kerem

Jerusalem, , Israel

Site Status

Health Corporation of Galilee Medical Center

Nahariya, , Israel

Site Status

Chaim Sheba Medical Center

Ramat Gan, , Israel

Site Status

Tel-Aviv Sourasky Medical Center

Tel Aviv, , Israel

Site Status

Shamir Medical Center (Assaf Harofeh)

Zrifin, , Israel

Site Status

A.O.U. di Ferrara

Ferrara, Emilia-Romagna, Italy

Site Status

AUSL della Romagna

Rimini, Emilia-Romagna, Italy

Site Status

ASST Papa Giovanni XXIII

Bergamo, Lombardy, Italy

Site Status

ASST Spedali Civili di Brescia

Brescia, Lombardy, Italy

Site Status

IRCCS Centro Cardiologico Monzino S.p.A

Milan, Lombardy, Italy

Site Status

Fondazione Policlinico di Monza

Monza Brianza, Lombardy, Italy

Site Status

AUSL Toscana Sud-Est

Arezzo, Tuscany, Italy

Site Status

Fondazione Toscana Gabriele Monasterio (FTGM)

Pisa, Tuscany, Italy

Site Status

A.O.U. Senese

Siena, Tuscany, Italy

Site Status

Uniwersytecki Szpital Kliniczny w Bialymstoku

Bialystok, , Poland

Site Status

10 Wojskowy Szpital Kliniczny z Poliklinika SPZOZ

Bydgoszcz, , Poland

Site Status

Szpital sw. Wincentego a Paulo

Gdynia, , Poland

Site Status

Samodzielny Publiczny Specjalistyczny Szpital Zachodni

Grodzisk Mazowiecki, , Poland

Site Status

Szpital Kliniczny Przemienienia Panskiego

Poznan, , Poland

Site Status

Szpital Wojewodzki Nr 2

Rzeszów, , Poland

Site Status

Uniwersyteckie Centrum Kliniczne Warszawskiego UM

Warsaw, , Poland

Site Status

Uniwersytecki Szpital Kliniczny UM we Wroclawiu

Wroclaw, , Poland

Site Status

Hospital de Cascais

Alcabideche, Lisbon District, Portugal

Site Status

CHS - Hospital Sao Bernardo

Setúbal, Setúbal District, Portugal

Site Status

CHL - Hospital Santo Andre

Leiria, , Portugal

Site Status

CHLO - Hospital Sao Francisco Xavier

Lisbon, , Portugal

Site Status

Hospital da Luz - Lisboa

Lisbon, , Portugal

Site Status

CHUP - Hospital Santo Antonio

Porto, , Portugal

Site Status

Hospital Álvaro Cunqueiro

Babio - Beade, Pontevedra, Spain

Site Status

Hospital del Mar

Barcelona, , Spain

Site Status

Hospital Ramón y Cajal

Madrid, , Spain

Site Status

Hospital Virgen de la Victoria

Málaga, , Spain

Site Status

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Site Status

Hospital General Universitario de Valencia

Valencia, , Spain

Site Status

Hospital Universitari i Politècnic La Fe

Valencia, , Spain

Site Status

Countries

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Austria Bulgaria Greece Hungary Israel Italy Poland Portugal Spain

References

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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 Aug 11. doi: 10.1002/ejhf.3801. Online ahead of print.

Reference Type DERIVED
PMID: 40788619 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37102974 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33188886 (View on PubMed)

Related Links

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http://www.clinicaltrialsregister.eu/

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

Other Identifiers

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2018-004059-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

17909

Identifier Type: -

Identifier Source: org_study_id

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