A Trial to Study BAY1753011 in Patients With Congestive Heart Failure

Heart Failure (HF) Clinical Trial

— AVANTI  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03901729
• Other study ID #: 17909
• Secondary ID: 2018-004059-18
• Status: Completed
• Phase: Phase 2
• Start date: May 29, 2019
• Est. completion date: May 21, 2021

Study information

• Verified date: April 2022
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 482
• Est. completion date: May 21, 2021
• Est. primary completion date: April 16, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure (HF)

Intervention

Drug:
• BAY 1753011
Tablet; 30mg or 5mg unit; 30mg once daily in the morning; Oral

Other:
• Placebo BAY 1753011
Tablet; Once daily in the morning; Oral

Drug:
• Furosemide
Tablet; 40mg unit; 80mg once daily in the morning; Oral

Other:
• Placebo Furosemide
Tablet; Once daily in the morning; Oral

Locations

Country	Name	City	State
Austria	Krankenhaus St. Josef Braunau	Braunau	Oberösterreich
Austria	Medizinische Universität Graz	Graz	Steiermark
Austria	Universitätsklinikum St. Pölten	St. Pölten	Niederösterreich
Austria	Klinik Floridsdorf - Krankenhaus Nord	Wien
Austria	Universitätsklinikum AKH Wien	Wien
Bulgaria	MHAT Haskovo	Haskovo
Bulgaria	Spec Hosp for Active Treatm in Cardiology Sv Georgi Pernik	Pernik
Bulgaria	UMHAT Dr. Georgi Stranski	Pleven
Bulgaria	Multiprofile Hospital for Active Treatment Medline Clinic	Plovdiv
Bulgaria	MHAT "Knyaginya Klementina - Sofia"EAD	Sofia
Bulgaria	NMTH Tzar Boris III	Sofia
Bulgaria	UMHAT Tsaritsa Joanna-ISUL EAD Sofia	Sofia
Greece	G. GENNIMATAS General State Hospital of Athens	Athens
Greece	University General Hospital of Athens "ATTIKON"	Chaidari - Athens
Greece	University General Hospital of Ioannina	Ioannina
Greece	KAT General Hospital of Athens	Kifisia / Athens	Attica
Greece	Univ. General Hospital of Larissa	Larissa
Greece	Konstantopoulio General Hospital of Nea Ionia - AGIA OLGA	Nea Ionia / Athens
Greece	"AHEPA" University General Hospital of Thessaloniki	Thessaloniki
Greece	Hippokration General Hospital of Thessaloniki	Thessaloniki
Hungary	Budai Irgalmasrendi Korhaz	Budapest
Hungary	Magyar Honvedseg Egeszsegugyi Kozpont Honvedkorhaz	Budapest
Hungary	University of Semmelweis/ Semmelweis Egyetem	Budapest
Hungary	Kanizsai Dorottya Hospital	Nagykanizsa
Hungary	Josa Andras Hospital	Nyiregyhaza
Hungary	Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz	Szekesfehervar
Hungary	Tolna Megyei Balassa Janos Korhaz	Szekszard
Hungary	Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz	Szolnok
Hungary	Zala Megyei Szent Rafael Korhaz	Zalaegerszeg
Israel	Barzilai Medical Center	Ashkelon
Israel	Rambam Health Corporation	Haifa
Israel	Hadassah Hebrew University Hospital Ein Kerem	Jerusalem
Israel	Health Corporation of Galilee Medical Center	Nahariya
Israel	Chaim Sheba Medical Center	Ramat Gan
Israel	Tel-Aviv Sourasky Medical Center	Tel Aviv
Israel	Shamir Medical Center (Assaf Harofeh)	Zrifin
Italy	AUSL Toscana Sud-Est	Arezzo	Toscana
Italy	ASST Papa Giovanni XXIII	Bergamo	Lombardia
Italy	ASST Spedali Civili di Brescia	Brescia	Lombardia
Italy	A.O.U. di Ferrara	Ferrara	Emilia-Romagna
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	A.O.U. Senese	Siena	Toscana
Poland	Uniwersytecki Szpital Kliniczny w Bialymstoku	Bialystok
Poland	10 Wojskowy Szpital Kliniczny z Poliklinika SPZOZ	Bydgoszcz
Poland	Szpital sw. Wincentego a Paulo	Gdynia
Poland	Samodzielny Publiczny Specjalistyczny Szpital Zachodni	Grodzisk Mazowiecki
Poland	Szpital Kliniczny Przemienienia Panskiego	Poznan
Poland	Szpital Wojewodzki Nr 2	Rzeszow
Poland	Uniwersyteckie Centrum Kliniczne Warszawskiego UM	Warszawa
Poland	Uniwersytecki Szpital Kliniczny UM we Wroclawiu	Wroclaw
Portugal	Hospital de Cascais	Alcabideche	Lisboa
Portugal	CHL - Hospital Santo Andre	Leiria
Portugal	CHLO - Hospital Sao Francisco Xavier	Lisboa
Portugal	Hospital da Luz - Lisboa	Lisboa
Portugal	CHUP - Hospital Santo Antonio	Porto
Portugal	CHS - Hospital Sao Bernardo	Setubal	Setúbal
Spain	Hospital Álvaro Cunqueiro	Babio - Beade	Pontevedra
Spain	Hospital del Mar	Barcelona
Spain	Hospital Ramón y Cajal	Madrid
Spain	Hospital Virgen de la Victoria	Málaga
Spain	Hospital Clínico Universitario de Valencia	Valencia
Spain	Hospital General Universitario de Valencia	Valencia
Spain	Hospital Universitari i Politècnic La Fe	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

Austria,  Bulgaria,  Greece,  Hungary,  Israel,  Italy,  Poland,  Portugal,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PART A: Change in body weight		Compare Day 30 (End of part A) with Day 1 (Start of part A)
Primary	PART A: Change in serum creatinine		Compare Day 30 (End of part A) with Day 1 (Start of part A)
Primary	PART B: Change in body weight		Compare Day 60 (End of part B) with Day 30 (Start of part B)
Primary	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	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)
Secondary	Change in augmentation index		Up to 60 days

External Links

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