A Trial to Study BAY1753011 in Patients With Congestive Heart Failure (AVANTI)

A Multicenter, Randomized, Parallel Group, Double Blind, Active and Placebo Controlled Study of BAY1753011, a Dual V1a/V2 Vasopressin Receptor Antagonist, in Patients With Congestive Heart Failure: AVANTI Study

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.

Study Overview

• Status: Completed
• Conditions: Heart Failure (HF)
• Intervention / Treatment: Drug: BAY 1753011; Other: Placebo BAY 1753011; Other: Placebo Furosemide; Drug: Furosemide

• Study Type: Interventional
• Enrollment (Actual): 482
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria, 1090
    • Universitätsklinikum AKH Wien
  • Wien, Austria, 1210
    • Klinik Floridsdorf - Krankenhaus Nord
  • Niederösterreich
    • St. Pölten, Niederösterreich, Austria, 3100
      • Universitätsklinikum St. Pölten
  • Oberösterreich
    • Braunau, Oberösterreich, Austria, 5280
      • Krankenhaus St. Josef Braunau
  • Steiermark
    • Graz, Steiermark, Austria, 8036
      • Medizinische Universität Graz
• Bulgaria
  • Haskovo, Bulgaria, 6300
    • MHAT Haskovo
  • Pernik, Bulgaria, 2300
    • Spec Hosp for Active Treatm in Cardiology Sv Georgi Pernik
  • Pleven, Bulgaria, 5800
    • UMHAT Dr. Georgi Stranski
  • Plovdiv, Bulgaria, 4000
    • Multiprofile Hospital for Active Treatment Medline Clinic
  • Sofia, Bulgaria, 1233
    • NMTH Tzar Boris III
  • Sofia, Bulgaria, 1527
    • UMHAT Tsaritsa Joanna-ISUL EAD Sofia
  • Sofia, Bulgaria, 1233
    • MHAT "Knyaginya Klementina - Sofia"EAD
• Greece
  • Athens, Greece, 11527
    • G. GENNIMATAS General State Hospital of Athens
  • Chaidari - Athens, Greece, 12462
    • University General Hospital of Athens "Attikon"
  • Ioannina, Greece, 45500
    • University General Hospital of Ioannina
  • Larissa, Greece, 41100
    • Univ. General Hospital of Larissa
  • Nea Ionia / Athens, Greece, 142 33
    • Konstantopoulio General Hospital of Nea Ionia - AGIA OLGA
  • Thessaloniki, Greece, 54642
    • Hippokration General Hospital of Thessaloniki
  • Thessaloniki, Greece, 54636
    • "AHEPA" University General Hospital of Thessaloniki
  • Attica
    • Kifisia / Athens, Attica, Greece, 14561
      • KAT General Hospital of Athens
• Hungary
  • Budapest, Hungary, 1023
    • Budai Irgalmasrendi Korhaz
  • Budapest, Hungary, 1122
    • University of Semmelweis/ Semmelweis Egyetem
  • Budapest, Hungary
    • Magyar Honvedseg Egeszsegugyi Kozpont Honvedkorhaz
  • Nagykanizsa, Hungary, 8800
    • Kanizsai Dorottya Hospital
  • Nyiregyhaza, Hungary, H-4400
    • Josa Andras Hospital
  • Szekesfehervar, Hungary, 8000
    • Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
  • Szekszard, Hungary, 7100
    • Tolna Megyei Balassa János Kórház
  • Szolnok, Hungary, 5000
    • Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz
  • Zalaegerszeg, Hungary, 8900
    • Zala Megyei Szent Rafael Korhaz
• Israel
  • Ashkelon, Israel, 7830604
    • Barzilai Medical Center
  • Haifa, Israel, 3109601
    • Rambam Health Corporation
  • Jerusalem, Israel, 9112001
    • Hadassah Hebrew University Hospital Ein Kerem
  • Nahariya, Israel, 22100
    • Health Corporation of Galilee Medical Center
  • Ramat Gan, Israel, 5262000
    • Chaim Sheba Medical Center
  • Tel Aviv, Israel, 6423906
    • Tel-Aviv Sourasky Medical Center
  • Zrifin, Israel, 7030000
    • Shamir Medical Center (Assaf Harofeh)
• Italy
  • Emilia-Romagna
    • Ferrara, Emilia-Romagna, Italy, 44124
      • A.O.U. di Ferrara
    • Rimini, Emilia-Romagna, Italy, 47923
      • AUSL della Romagna
  • Lombardia
    • Bergamo, Lombardia, Italy, 24127
      • ASST Papa Giovanni XXIII
    • Brescia, Lombardia, Italy, 25123
      • Asst Spedali Civili Di Brescia
    • Milano, Lombardia, Italy, 20138
      • IRCCS Centro Cardiologico Monzino S.p.A
    • Monza Brianza, Lombardia, Italy, 20900
      • Fondazione Policlinico di Monza
  • Toscana
    • Arezzo, Toscana, Italy, 52044
      • AUSL Toscana Sud-Est
    • Pisa, Toscana, Italy, 56124
      • Fondazione Toscana Gabriele Monasterio (FTGM)
    • Siena, Toscana, Italy, 53100
      • A.O.U. Senese
• Poland
  • Bialystok, Poland, 15-276
    • Uniwersytecki Szpital Kliniczny w Bialymstoku
  • Bydgoszcz, Poland, 85-681
    • 10 Wojskowy Szpital Kliniczny z Poliklinika SPZOZ
  • Gdynia, Poland, 81-348
    • Szpital sw. Wincentego a Paulo
  • Grodzisk Mazowiecki, Poland, 05-825
    • Samodzielny Publiczny Specjalistyczny Szpital Zachodni
  • Poznan, Poland, 61-848
    • Szpital Kliniczny Przemienienia Pańskiego
  • Rzeszow, Poland, 35-301
    • Szpital Wojewodzki Nr 2
  • Warszawa, Poland, 02-097
    • Uniwersyteckie Centrum Kliniczne Warszawskiego UM
  • Wroclaw, Poland, 50-556
    • Uniwersytecki Szpital Kliniczny UM we Wroclawiu
• Portugal
  • Leiria, Portugal, 2410-197
    • CHL - Hospital Santo Andre
  • Lisboa, Portugal, 1449-005
    • CHLO - Hospital Sao Francisco Xavier
  • Lisboa, Portugal, 1500-650
    • Hospital da Luz - Lisboa
  • Porto, Portugal, 4099-001
    • CHUP - Hospital Santo Antonio
  • Lisboa
    • Alcabideche, Lisboa, Portugal, 2755-009
      • Hospital de Cascais
  • Setúbal
    • Setubal, Setúbal, Portugal, 2900-446
      • CHS - Hospital Sao Bernardo
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal
  • Málaga, Spain, 29010
    • Hospital Virgen de la Victoria
  • Valencia, Spain, 46026
    • Hospital Universitari i Politècnic La Fe
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Valencia, Spain, 46014
    • Hospital General Universitario de Valencia
  • Pontevedra
    • Babio - Beade, Pontevedra, Spain, 36312
      • Hospital Alvaro Cunqueiro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; BAY1753011 30mg in addition to standard of care (SoC) for part A and part B	Drug: BAY 1753011; Tablet; 30mg or 5mg unit; 30mg once daily in the morning; Oral
Placebo Comparator: Arm 2; Placebo of BAY1753011 in addition to SoC for part A and part B	Other: Placebo BAY 1753011; Tablet; Once daily in the morning; Oral
Experimental: Arm 1-A; BAY1753011 30mg in addition to Placebo Furosemide 80mg for part B	Drug: BAY 1753011; Tablet; 30mg or 5mg unit; 30mg once daily in the morning; Oral; Other: Placebo Furosemide; Tablet; Once daily in the morning; Oral
Active Comparator: Arm 1-B; Furosemide 80mg in addition to Placebo BAY1753011 30mg for part B	Other: Placebo BAY 1753011; Tablet; Once daily in the morning; Oral; Drug: Furosemide; Tablet; 40mg unit; 80mg once daily in the morning; Oral
Experimental: Arm 2-A; BAY1753011 30mg in addition to Placebo Furosemide 80mg for part B	Drug: BAY 1753011; Tablet; 30mg or 5mg unit; 30mg once daily in the morning; Oral; Other: Placebo Furosemide; Tablet; Once daily in the morning; Oral
Active Comparator: Arm 2-B; Furosemide 80mg in addition to Placebo BAY1753011 30mg for part B	Other: Placebo BAY 1753011; Tablet; Once daily in the morning; Oral; Drug: Furosemide; Tablet; 40mg unit; 80mg once daily in the morning; Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• 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.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2019
• Primary Completion (Actual): April 16, 2021
• Study Completion (Actual): May 21, 2021

Study Registration Dates

• First Submitted: April 2, 2019
• First Submitted That Met QC Criteria: April 2, 2019
• First Posted (Actual): April 3, 2019

Study Record Updates

• Last Update Posted (Actual): April 18, 2022
• Last Update Submitted That Met QC Criteria: April 11, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Heart failure with preserved ejection fraction (HFpEF); Heart failure with reduced ejection fraction (HFrEF); Chronic heart failure (CHF); Heart failure with mid-range ejection fraction (HFmrEF)
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Furosemide
• Other Study ID Numbers: 17909; 2018-004059-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

IPD Plan Description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access.

As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No