Clinical trial NCT03901729: A Trial to Study BAY1753011 in Patients With Congestive Heart Failure
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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)
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2019-04-03
Enrollment: 482
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: PART A: Change in body weight
timeFrame: Compare Day 30 (End of part A) with Day 1 (Start of part A)
measure: PART A: Change in serum creatinine
timeFrame: Compare Day 30 (End of part A) with Day 1 (Start of part A)
measure: PART B: Change in body weight
timeFrame: Compare Day 60 (End of part B) with Day 30 (Start of part B)
measure: PART B: Change in log transformed blood urea nitrogen (BUN)/creatinine ratio
timeFrame: Compare Day 60 (End of part B) with Day 30 (Start of part B)
Secondary outcomes:
measure: Incidence of Treatment-emergent adverse event (including Serious adverse event)
timeFrame: From the time of first study drug administration up to 7 days after the last dose of study drug (Day 60)
measure: Change in augmentation index
timeFrame: Up to 60 days
Other outcomes:
Locations:
city: St. Pölten
country: Austria
facility: Universitätsklinikum St. Pölten
state: Niederösterreich
city: Braunau
country: Austria
facility: Krankenhaus St. Josef Braunau
state: Oberösterreich
city: Graz
country: Austria
facility: Medizinische Universität Graz
state: Steiermark
city: Wien
country: Austria
facility: Universitätsklinikum AKH Wien
city: Wien
country: Austria
facility: Klinik Floridsdorf - Krankenhaus Nord
city: Haskovo
country: Bulgaria
facility: MHAT Haskovo
city: Pernik
country: Bulgaria
facility: Spec Hosp for Active Treatm in Cardiology Sv Georgi Pernik
city: Pleven
country: Bulgaria
facility: UMHAT Dr. Georgi Stranski
city: Plovdiv
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Medline Clinic
city: Sofia
country: Bulgaria
facility: MHAT "Knyaginya Klementina - Sofia"EAD
city: Sofia
country: Bulgaria
facility: NMTH Tzar Boris III
city: Sofia
country: Bulgaria
facility: UMHAT Tsaritsa Joanna-ISUL EAD Sofia
city: Kifisia / Athens
country: Greece
facility: KAT General Hospital of Athens
state: Attica
city: Athens
country: Greece
facility: G. GENNIMATAS General State Hospital of Athens
city: Chaidari - Athens
country: Greece
facility: University General Hospital of Athens "ATTIKON"
city: Ioannina
country: Greece
facility: University General Hospital of Ioannina
city: Larissa
country: Greece
facility: Univ. General Hospital of Larissa
city: Nea Ionia / Athens
country: Greece
facility: Konstantopoulio General Hospital of Nea Ionia - AGIA OLGA
city: Thessaloniki
country: Greece
facility: "AHEPA" University General Hospital of Thessaloniki
city: Thessaloniki
country: Greece
facility: Hippokration General Hospital of Thessaloniki
city: Budapest
country: Hungary
facility: Budai Irgalmasrendi Korhaz
city: Budapest
country: Hungary
facility: University of Semmelweis/ Semmelweis Egyetem
city: Budapest
country: Hungary
facility: Magyar Honvedseg Egeszsegugyi Kozpont Honvedkorhaz
city: Nagykanizsa
country: Hungary
facility: Kanizsai Dorottya Hospital
city: Nyiregyhaza
country: Hungary
facility: Josa Andras Hospital
city: Szekesfehervar
country: Hungary
facility: Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
city: Szekszard
country: Hungary
facility: Tolna Megyei Balassa Janos Korhaz
city: Szolnok
country: Hungary
facility: Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz
city: Zalaegerszeg
country: Hungary
facility: Zala Megyei Szent Rafael Korhaz
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Haifa
country: Israel
facility: Rambam Health Corporation
city: Jerusalem
country: Israel
facility: Hadassah Hebrew University Hospital Ein Kerem
city: Nahariya
country: Israel
facility: Health Corporation of Galilee Medical Center
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
city: Zrifin
country: Israel
facility: Shamir Medical Center (Assaf Harofeh)
city: Ferrara
country: Italy
facility: A.O.U. di Ferrara
state: Emilia-Romagna
city: Rimini
country: Italy
facility: AUSL della Romagna
state: Emilia-Romagna
city: Bergamo
country: Italy
facility: ASST Papa Giovanni XXIII
state: Lombardia
city: Brescia
country: Italy
facility: ASST Spedali Civili di Brescia
state: Lombardia
city: Milano
country: Italy
facility: IRCCS Centro Cardiologico Monzino S.p.A
state: Lombardia
city: Monza Brianza
country: Italy
facility: Fondazione Policlinico di Monza
state: Lombardia
city: Arezzo
country: Italy
facility: AUSL Toscana Sud-Est
state: Toscana
city: Pisa
country: Italy
facility: Fondazione Toscana Gabriele Monasterio (FTGM)
state: Toscana
city: Siena
country: Italy
facility: A.O.U. Senese
state: Toscana
city: Bialystok
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Bialymstoku
city: Bydgoszcz
country: Poland
facility: 10 Wojskowy Szpital Kliniczny z Poliklinika SPZOZ
city: Gdynia
country: Poland
facility: Szpital sw. Wincentego a Paulo
city: Grodzisk Mazowiecki
country: Poland
facility: Samodzielny Publiczny Specjalistyczny Szpital Zachodni
city: Poznan
country: Poland
facility: Szpital Kliniczny Przemienienia Panskiego
city: Rzeszow
country: Poland
facility: Szpital Wojewodzki Nr 2
city: Warszawa
country: Poland
facility: Uniwersyteckie Centrum Kliniczne Warszawskiego UM
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny UM we Wroclawiu
city: Alcabideche
country: Portugal
facility: Hospital de Cascais
state: Lisboa
city: Setubal
country: Portugal
facility: CHS - Hospital Sao Bernardo
state: Setúbal
city: Leiria
country: Portugal
facility: CHL - Hospital Santo Andre
city: Lisboa
country: Portugal
facility: CHLO - Hospital Sao Francisco Xavier
city: Lisboa
country: Portugal
facility: Hospital da Luz - Lisboa
city: Porto
country: Portugal
facility: CHUP - Hospital Santo Antonio
city: Babio - Beade
country: Spain
facility: Hospital Álvaro Cunqueiro
state: Pontevedra
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Málaga
country: Spain
facility: Hospital Virgen de la Victoria
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitari i Politècnic La Fe
Study officials:
References:
citation: 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.