Clinical trial NCT04218266: Study to Gather Information About the Proper Dosing of the Oral FXIa Inhibitor BAY 2433334 and to Compare the Safety of the Study Drug to Apixaban, a Non-vitamin K Oral Anticoagulant (NOAC) in Patients With Irregular Heartbeat (Atrial Fibrillation) That Can Lead to Heart-related Complications.
Official title: Multicenter, Randomized, Active Comparator-controlled, Double-blind, Double-dummy, Parallel Group, Dose-finding Phase 2 Study to Compare the Safety of the Oral FXIa Inhibitor BAY2433334 to Apixaban in Patients With Atrial Fibrillation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atrial Fibrillation (AF)
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2020-01-06
Enrollment: 755
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to try to find the best dose of the new drug BAY 2433334 to give to participants and to look at how well BAY 2433334 works in patients with irregular heartbeat (atrial fibrillation) that can lead to blood clots, stroke and other heart-related complications. In addition researchers want to compare the safety of the study drug to apixaban, a non-vitamin K oral anticoagulant (NOAC) in patients with atrial fibrillation. This study is also done to learn how the drug in this study moves into, through and out of the body. BAY 2433334, works by blocking a step of the blood clotting process in our body and thins the blood and is a so called oral FXIa inhibitor.

Apixaban, works by reducing the production of blood clotting factors in our body and thins the blood and is a so called non-vitamin K oral anticoagulant (NOAC). Thinning the blood can prevent you from blood clots which can cause a stroke.


Eligibility criteria: Inclusion Criteria:

* Participant must be 45 years of age or older at the time of signing the informed consent.
* Participant with AF documented by ECG evidence with

  * CHA2DS2-VASc score ≥ 2 if male or CHA2DS2-VASc score ≥ 3 if female
  * Indication for treatment with an oral anticoagulant in

    * any participant currently not treated with an oral anticoagulant (e.g. treatment naïve) or alternatively,
    * participant on a NOAC in case of at least one bleeding risk feature (history of a prior bleed within the last 12 months requiring medical attention and / or moderate renal dysfunction with eGFR 30-50 ml/min and / or current clinically indicated antiplatelet therapy with Acetylsalicylic acid(ASA) ≤ 100 mg)
* Written informed consent

Exclusion Criteria:

* Mechanical heart valve prosthesis
* Any degree of rheumatic mitral stenosis or moderate-to-severe, non-rheumatic mitral stenosis
* Atrial fibrillation due to a reversible cause, participants in sinus rhythm after successful ablation, or plan for cardioversion or ablation during study conduct
* Requirement for chronic anticoagulation (for a different indication than AF) or antiplatelet therapy (up to 100 mg ASA is allowed). Anticipated need for chronic therapy with Nonsteroidal anti-inflammatory drugs (NSAIDs)
* Treated with a Vitamin K antagonist in the 30 days prior to screening

Primary outcomes:
measure: Number of Participants With Composite of International Society on Thrombosis and Hemostasis (ISTH) Major Bleeding or Clinically Relevant Non-major (CRNM) Bleeding
timeFrame: After the first administration of study intervention with an average administration of 12 weeks (but not starting after more than 2 days after the last administration)
Secondary outcomes:
measure: Number of Participants With All Bleeding
timeFrame: After the first administration of study intervention with an average administration of 12 weeks (but not starting after more than 2 days after the last administration)
measure: Number of Participants With ISTH Major Bleeding
timeFrame: After the first administration of study intervention with an average administration of 12 weeks (but not starting after more than 2 days after the last administration)
measure: Number of Participants of ISTH Clinically Relevant Non-major (CRNM) Bleeding
timeFrame: After the first administration of study intervention with an average administration of 12 weeks (but not starting after more than 2 days after the last administration)
measure: Number of Participants With ISTH Minor Bleeding
timeFrame: After the first administration of study intervention with an average administration of 12 weeks (but not starting after more than 2 days after the last administration)
Other outcomes:
Locations:
city: Braunau
country: Austria
facility: Krankenhaus St. Josef Braunau
state: Oberösterreich
city: Linz
country: Austria
facility: Ordensklinikum Linz GmbH Elisabethinen
state: Oberösterreich
city: Graz
country: Austria
facility: Medizinische Universität Graz
state: Steiermark
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
state: Tirol
city: Feldkirch
country: Austria
facility: Landeskrankenhaus Feldkirch
state: Vorarlberg
city: Salzburg
country: Austria
facility: Uniklinikum Salzburg - Landeskrankenhaus
city: Wien
country: Austria
facility: Universitätsklinikum AKH Wien
city: Wien
country: Austria
facility: Klinik Floridsdorf - Krankenhaus Nord
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
state: Vlaams Brabant
city: Bonheiden
country: Belgium
facility: Imeldaziekenhuis - St-Elisabethkliniek
city: Brugge
country: Belgium
facility: AZ St-Jan Brugge Oostende AV
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis
city: Mechelen
country: Belgium
facility: VZW Emmaus
city: Roeselare
country: Belgium
facility: AZ Delta
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre
state: Nova Scotia
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Montreal
country: Canada
facility: Clinique Sante Cardio MC
state: Quebec
city: Ste-Foy
country: Canada
facility: Institut universitaire de cardiologie et de pneumologie
state: Quebec
city: Plzen
country: Czechia
facility: Fakultni nemocnice Plzen - Lochotin
city: Praha 10
country: Czechia
facility: Fakultni nemocnice Kralovske Vinohrady
city: Praha 4
country: Czechia
facility: Institut Klinicke a Experimentalni Mediciny
city: Praha 5
country: Czechia
facility: Fakultni nemocnice v Motole
city: Slany
country: Czechia
facility: Nemocnice Slany
city: Zlin
country: Czechia
facility: Krajska nemocnice T. Bati, a.s.
city: Creteil
country: France
facility: Hôpital Henri Mondor
city: La Roche Sur Yon Cedex
country: France
facility: Centre Hospitalier Départemental Vendée
city: Le Coudray
country: France
facility: Centre Hospitalier Louis Pasteur
city: Paris
country: France
facility: Hopital Bichat - Paris
city: Saint Brieuc
country: France
facility: Centre Hospitalier Régional - Saint Brieuc
city: Toulouse
country: France
facility: Hôpital de Rangueil - Toulouse
city: Valenciennes Cedex
country: France
facility: Centre Hospitalier - Valenciennes Cedex
city: Balatonfured
country: Hungary
facility: Tagore Medical Center
city: Budapest
country: Hungary
facility: University of Semmelweis/ Semmelweis Egyetem
city: Budapest
country: Hungary
facility: Magyar Honvedseg Egeszsegugyi Kozpont
city: Nagykanizsa
country: Hungary
facility: Kanizsai Dorottya Hospital
city: Nyiregyhaza
country: Hungary
facility: Medifarma-98 Egeszsegugyi, Kereskedelmi es Szolgaltato Kft.
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem Klinikai Kozpont
city: Szekszard
country: Hungary
facility: Tolna Megyei Balassa Janos Korhaz
city: Szentes
country: Hungary
facility: Csongrad-Csanad Megyei Dr. Bugyi Istvan Korhaz
city: Roma
country: Italy
facility: A.O.U. Policlinico Umberto I
state: Lazio
city: Genova
country: Italy
facility: IRCCS Ospedale Policlinico San Martino
state: Liguria
city: Brescia
country: Italy
facility: ASST Spedali Civili di Brescia
state: Lombardia
city: Ascoli Piceno
country: Italy
facility: ASUR Marche - Area Vasta 5
state: Marche
city: Arezzo
country: Italy
facility: AUSL Toscana Sud-Est
state: Toscana
city: Arezzo
country: Italy
facility: AUSL Toscana Sud-Est
state: Toscana
city: Perugia
country: Italy
facility: A.O. di Perugia
state: Umbria
city: Itoshima
country: Japan
facility: Nakamura Cardiovascular Clinic
state: Fukuoka
city: Himeji
country: Japan
facility: Hyogo Prefectural Harima-Himeji General Medical Center
state: Hyogo
city: Miura-gun
country: Japan
facility: Hayama Heart Center
state: Kanagawa
city: Kishiwada
country: Japan
facility: Kishiwada Tokushukai Hospital
state: Osaka
city: Yao
country: Japan
facility: Yao Tokushukai General Hospital
state: Osaka
city: Adachi-ku
country: Japan
facility: Nishiarai Heart Central Clinic
state: Tokyo
city: Hachioji
country: Japan
facility: Minamino Cardiovascular Hospital
state: Tokyo
city: Hachioji
country: Japan
facility: Tokyo Angel Hospital
state: Tokyo
city: Koto-ku
country: Japan
facility: Koto Hospital
state: Tokyo
city: Daugavpils
country: Latvia
facility: Doctor's Practice in Cardiology
city: Daugavpils
country: Latvia
facility: Daugavpils Regional Hospital
city: Liepaja
country: Latvia
facility: Liepaja Regional Hospital
city: Riga
country: Latvia
facility: 1st Riga Clinical Hospital
city: Riga
country: Latvia
facility: P. Stradins Clinical University Hospital
city: Riga
country: Latvia
facility: Riga East Clinical University Hospital "Gailezers"
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum (AMC)
city: Arnhem
country: Netherlands
facility: Ziekenhuis Rijnstate
city: Breda
country: Netherlands
facility: Amphia Ziekenhuis, locatie Molengracht
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis, Dordwijk
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Groningen
country: Netherlands
facility: Martini Ziekenhuis, Locatie van Swieten
city: Haarlem
country: Netherlands
facility: Spaarne Gasthuis - locatie Zuid
city: Maastricht
country: Netherlands
facility: Maastricht UMC
city: L'Hospitalet de Llobregat
country: Spain
facility: Ciutat Sanitària i Universitària de Bellvitge
state: Barcelona
city: Barcelona
country: Spain
facility: Ciutat Sanitària i Universitaria de la Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i de Sant Pau | Cardiología
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Málaga
country: Spain
facility: Hospital Virgen de la Victoria
city: Falun
country: Sweden
facility: Falu Lasarett
city: Lund
country: Sweden
facility: Clemenstorget Hjärtmottagning
city: Skellefteå
country: Sweden
facility: Skellefteå Lasarett
city: Stockholm
country: Sweden
facility: Södersjukhuset AB
city: Stockholm
country: Sweden
facility: Danderyds sjukhus
city: Örebro
country: Sweden
facility: Avdelningen för kliniska prövningar AKP
city: Östersund
country: Sweden
facility: Östersunds Sjukhus
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau
state: Aargau
city: Basel
country: Switzerland
facility: Universitätsspital Basel
state: Basel-Stadt
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
state: Sankt Gallen
city: Bern
country: Switzerland
facility: Inselspital Universitätsspital Bern
city: Genève
country: Switzerland
facility: Hôpital Cantonal Universitaire de Genève
city: Lugano
country: Switzerland
facility: Ospedale regionale di Lugano
city: Ely
country: United Kingdom
facility: Staploe Medical Centre
state: Cambridgeshire
city: Welwyn Garden City
country: United Kingdom
facility: Queen Elizabeth II Hospital
state: Hertfordshire
city: Harrow
country: United Kingdom
facility: Northwick Park Hospital
state: London
city: Chichester
country: United Kingdom
facility: St Richard's Hospital
state: West Sussex
city: Liverpool
country: United Kingdom
facility: Heart and Chest Hospital
Study officials:
References:
citation: Piccini JP, Caso V, Connolly SJ, Fox KAA, Oldgren J, Jones WS, Gorog DA, Durdil V, Viethen T, Neumann C, Mundl H, Patel MR; PACIFIC-AF Investigators. Safety of the oral factor XIa inhibitor asundexian compared with apixaban in patients with atrial fibrillation (PACIFIC-AF): a multicentre, randomised, double-blind, double-dummy, dose-finding phase 2 study. Lancet. 2022 Apr 9;399(10333):1383-1390. doi: 10.1016/S0140-6736(22)00456-1. Epub 2022 Apr 3.