check_circleStudy Completed

Atrial fibrillation (AF)

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.

Trial purpose

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.

Key Participants Requirements

Sex

All

Age

45 - N/A
  • - 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
  • - 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

Trial summary

Enrollment Goal
755
Trial Dates
January 2020 - October 2021
Phase
Phase 2
Could I Receive a placebo
No
Products
Asundexian (BAY2433334)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Krajska nemocnice T. Bati, a.s.Zlin, 762 75, Czechia
Completed
Nemocnice SlanySlany, 274 01, Czechia
Completed
Universitätsspital BaselBasel, 4031, Switzerland
Completed
Inselspital Universitätsspital BernBern, 3010, Switzerland
Withdrawn
Kantonsspital WinterthurWinterthur, 8401, Switzerland
Completed
Kantonsspital St. GallenSt. Gallen, 9007, Switzerland
Completed
Kantonsspital AarauAarau, 5001, Switzerland
Withdrawn
Luzerner KantonsspitalLuzern, 6000, Switzerland
Completed
Ospedale regionale di LuganoLugano, 6900, Switzerland
Completed
Hôpital Cantonal Universitaire de GenèveGenève, 1211, Switzerland
Completed
Jessa ZiekenhuisHASSELT, 3500, Belgium
Completed
AZ St-Jan Brugge Oostende AVBRUGGE, 8000, Belgium
Completed
Imeldaziekenhuis - St-ElisabethkliniekBONHEIDEN, 2820, Belgium
Completed
UZ AntwerpenEDEGEM, 2650, Belgium
Completed
VZW EmmausMECHELEN, 2800, Belgium
Completed
UZ Leuven GasthuisbergLEUVEN, 3000, Belgium
Withdrawn
Hospital Arnau de Vilanova de ValenciaValencia, 46015, Spain
Completed
Ciutat Sanitària i Universitària de BellvitgeL'Hospitalet de Llobregat, 08907, Spain
Completed
Hospital Universitario 12 de OctubreMadrid, 28041, Spain
Completed
Hospital Virgen de la VictoriaMálaga, 29010, Spain
Withdrawn
Hospital del MarBarcelona, 08003, Spain
Completed
Ciutat Sanitària i Universitaria de la Vall d'HebronBarcelona, 08035, Spain
Withdrawn
Hospital Ramon y Cajal | CardiologiaMadrid, 28034, Spain
Completed
Hospital de la Santa Creu i de Sant Pau | CardiologíaBarcelona, 08041, Spain
Completed
AZ DeltaROESELARE, 8800, Belgium
Completed
Heart and Chest HospitalLiverpool, L14 3PE, United Kingdom
Completed
Staploe Medical CentreEly, CB7 5SQ, United Kingdom
Completed
Queen Elizabeth II HospitalWelwyn Garden City, AL7 4HQ, United Kingdom
Withdrawn
Chesterfield Royal HospitalChesterfield, S44 5DX, United Kingdom
Completed
Northwick Park HospitalHarrow, HA1 3UJ, United Kingdom
Withdrawn
University Hospital of WalesCardiff, CF14 4XW, United Kingdom
Withdrawn
Royal Cornwall HospitalTruro, TR1 3LJ, United Kingdom
Completed
Magyar Honvedseg Egeszsegugyi KozpontBudapest, Hungary
Completed
Tolna Megyei Balassa Janos KorhazSzekszard, 7100, Hungary
Completed
Csongrad-Csanad Megyei Dr. Bugyi Istvan KorhazSzentes, 6600, Hungary
Completed
Kanizsai Dorottya HospitalNagykanizsa, 8800, Hungary
Completed
University of Semmelweis/ Semmelweis EgyetemBudapest, 1122, Hungary
Completed
Pecsi Tudomanyegyetem Klinikai KozpontPecs, 7624, Hungary
Withdrawn
Magyar Honvedseg Egeszsegugyi KozpontBudapest, 1134, Hungary
Completed
Medifarma-98 Egeszsegugyi, Kereskedelmi es Szolgaltato Kft.Nyiregyhaza, 4400, Hungary
Withdrawn
Hamilton Health SciencesHamilton, L8L2X2, Canada
Completed
Clinique Sante Cardio MCMontreal, H1T 3Y7, Canada
Withdrawn
Royal Alexandra HospitalEdmonton, T5H 3V9, Canada
Withdrawn
St. Michael's Hospital Health CentreToronto, M5B 1W8, Canada
Withdrawn
Cambridge Cardiac Care CenterCambridge, N1R 6V6, Canada
Completed
Institut universitaire de cardiologie et de pneumologieSte-Foy, G1V 4G5, Canada
Completed
Fakultni nemocnice Kralovske VinohradyPraha 10, 100 34, Czechia
Completed
Institut Klinicke a Experimentalni MedicinyPraha 4, 140 21, Czechia
Withdrawn
Oblastni Nemocnice KladnoKladno, 27259, Czechia
Completed
Fakultni nemocnice Plzen - LochotinPlzen, 304 60, Czechia
Withdrawn
Nemocnice Pardubickeho kraje a.s., Orlickoustecka nemocniceUsti nad Orlici, 56218, Czechia
Completed
Fakultni nemocnice v MotolePraha 5, 150 06, Czechia
Withdrawn
Ventspils HospitalVentspils, LV-3601, Latvia
Completed
Liepaja Regional HospitalLiepaja, LV-3414, Latvia
Completed
1st Riga Clinical HospitalRiga, LV-1001, Latvia
Completed
P. Stradins Clinical University HospitalRiga, LV-1002, Latvia
Completed
Daugavpils Regional HospitalDaugavpils, LV-5417, Latvia
Completed
Riga East Clinical University Hospital "Gailezers"Riga, LV-1038, Latvia
Completed
Doctor's Practice in CardiologyDaugavpils, LV-5401, Latvia
Completed
Riga East Clinical University Hospital "Gailezers"Riga, LV-1038, Latvia
Completed
AUSL Toscana Sud-EstArezzo, 52100, Italy
Completed
AUSL Toscana Sud-EstArezzo, 52044, Italy
Completed
A.O. di PerugiaPerugia, 06129, Italy
Completed
ASUR Marche - Area Vasta 5Ascoli Piceno, 63074, Italy
Completed
IRCCS Ospedale Policlinico San MartinoGenova, 16132, Italy
Completed
ASST Spedali Civili di BresciaBrescia, 25123, Italy
Withdrawn
A.O. Ospedali Riuniti Villa Sofia-CervelloPalermo, 90146, Italy
Completed
A.O.U. Policlinico Umberto IRoma, 00161, Italy
Completed
Krankenhaus St. Josef BraunauBraunau, 5280, Austria
Completed
Klinik Floridsdorf - Krankenhaus NordWien, 1210, Austria
Completed
Landeskrankenhaus FeldkirchFeldkirch, 6807, Austria
Completed
Uniklinikum Salzburg - LandeskrankenhausSalzburg, 5020, Austria
Completed
Universitätsklinikum AKH WienWien, 1090, Austria
Completed
Medizinische Universität GrazGraz, 8036, Austria
Completed
Medizinische Universität InnsbruckInnsbruck, 6020, Austria
Completed
Ordensklinikum Linz GmbH ElisabethinenLinz, 4020, Austria
Completed
Hôpital Henri MondorCRETEIL, 94010, France
Completed
Centre Hospitalier Régional - Saint BrieucSAINT BRIEUC, 22000, France
Completed
Centre Hospitalier Départemental VendéeLA ROCHE SUR YON CEDEX, 85025, France
Completed
Centre Hospitalier Louis PasteurLE COUDRAY, 28630, France
Completed
Hopital Bichat - ParisPARIS, 75018, France
Completed
Centre Hospitalier - Valenciennes CedexVALENCIENNES CEDEX, 59322, France
Completed
Hôpital de Rangueil - ToulouseTOULOUSE, 31403, France
Withdrawn
Hopital de Cardiologie - LilleLILLE cedex, 59037, France
Completed
Queen Elizabeth II Health Sciences CentreHalifax, B3H 3A7, Canada
Completed
Montreal Heart InstituteMontreal, H1T 1C8, Canada
Withdrawn
H. Hartziekenhuis MolMOL, 2400, Belgium
Withdrawn
SU/ÖstraGöteborg, 416 85, Sweden
Completed
Clemenstorget HjärtmottagningLund, 222 21, Sweden
Completed
Danderyds sjukhusStockholm, 182 88, Sweden
Completed
Avdelningen för kliniska prövningar AKPÖrebro, 703 62, Sweden
Completed
Södersjukhuset ABStockholm, 118 83, Sweden
Completed
Skellefteå LasarettSkellefteå, 931 86, Sweden
Completed
Falu LasarettFalun, 791 82, Sweden
Completed
Östersunds SjukhusÖstersund, 831 83, Sweden
Completed
Koto HospitalKoto-ku, 136-0072, Japan
Completed
Kishiwada Tokushukai HospitalKishiwada, 596-0042, Japan
Completed
Nishiarai Heart Central ClinicAdachi-ku, 123-0845, Japan
Completed
Nakamura Cardiovascular ClinicItoshima, 819-1104, Japan
Completed
Hyogo Prefectural Harima-Himeji General Medical CenterHimeji, 670-8560, Japan
Completed
Tokyo Angel HospitalHachioji, 193-0811, Japan
Completed
Hayama Heart CenterMiura-gun, 240-0116, Japan
Completed
Yao Tokushukai General HospitalYao, 581-0011, Japan
Completed
Minamino Cardiovascular HospitalHachioji, 192-0918, Japan
Completed
Academisch Medisch Centrum (AMC)AMSTERDAM, 1105 AZ, Netherlands
Completed
Maastricht UMCMAASTRICHT, 6229 HX, Netherlands
Completed
Amphia Ziekenhuis, locatie MolengrachtBREDA, 4818 CK, Netherlands
Completed
Martini Ziekenhuis, Locatie van SwietenGRONINGEN, 9728 NT, Netherlands
Completed
Ziekenhuis RijnstateARNHEM, 6815 AD, Netherlands
Completed
Spaarne Gasthuis - locatie ZuidHAARLEM, 2035 RC, Netherlands
Completed
Albert Schweitzer Ziekenhuis, DordwijkDORDRECHT, 3318 AT, Netherlands
Completed
Medisch Spectrum TwenteENSCHEDE, 7511 JX, Netherlands
Completed
St Richard's HospitalChichester, PO19 6SE, United Kingdom
Completed
Tagore Medical CenterBalatonfured, 8230, Hungary

Primary Outcome

  • Number of participants with composite of International Society on Thrombosis and Hemostasis (ISTH) major bleeding or clinically relevant non-major (CRNM) bleeding
    ISTH Major Bleeding criteria: 1. Fatal bleeding, and/or 2. Symptomatic bleeding in a critical area or organ (intracranial, intraocular, intraspinal, pericardial, retroperitoneal, intraarticular, or intramuscular with compartment syndrome), and/or 3. Clinically overt bleeding associated with a recent decrease in the hemoglobin level of ≥ 2 g/dL (20 g/L; 1.24 mmol/L) compared to the most recent hemoglobin value available before the event, and/or 4. Clinically overt bleeding leading to transfusion of 2 or more units of packed red blood cells or whole blood. ISTH Clinically Relevant Non-Major Bleeding is considered any sign or symptom of hemorrhage that does not fit the criteria for the ISTH definition of major bleeding, but does meet at least one of the following criteria 1. requiring medical intervention by a healthcare professional. 2. leading to hospitalization or increased level of care. 3. prompting a face to face (i.e. not just a telephone or electronic communication) evaluation.
    date_rangeTime Frame:
    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 Outcome

  • Number of participants with all bleeding
    Adjudication of all bleeding events was performed by members of the Clinical events committee (CEC) who reviewed events in a blinded fashion and adjudicated and classified the following events in a consistent and unbiased manner according to the following classifications: ISTH (major, clinically relevant non-major and minor); Thrombolysis in myocardial infarction (TIMI major, minor, requiring medical attention, minimal); Bleeding Academic Research Consortium (BARC type 1, 2, 3, 5).
    date_rangeTime Frame:
    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)
  • Number of participants with ISTH major bleeding
    ISTH Major Bleeding criteria: 1. Fatal bleeding, and/or 2. Symptomatic bleeding in a critical area or organ (intracranial, intraocular, intraspinal, pericardial, retroperitoneal, intraarticular, or intramuscular with compartment syndrome), and/or 3. Clinically overt bleeding associated with a recent decrease in the hemoglobin level of ≥ 2 g/dL (20 g/L; 1.24 mmol/L) compared to the most recent hemoglobin value available before the event, and/or 4. Clinically overt bleeding leading to transfusion of 2 or more units of packed red blood cells or whole blood.
    date_rangeTime Frame:
    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)
  • Number of participants of ISTH clinically relevant non-major (CRNM) bleeding
    ISTH Clinically Relevant Non-Major Bleeding is considered any sign or symptom of hemorrhage that does not fit the criteria for the ISTH definition of major bleeding, but does meet at least one of the following criteria 1. requiring medical intervention by a healthcare professional. 2. leading to hospitalization or increased level of care. 3. prompting a face to face (i.e. not just a telephone or electronic communication) evaluation.
    date_rangeTime Frame:
    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)
  • Number of participants with ISTH minor bleeding
    All other overt bleeding episodes not meeting ISTH Major Bleeding criteria or clinically relevant non major bleeding were classified as minor bleeding.
    date_rangeTime Frame:
    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)

Trial design

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
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Randomized
Blinding
N/A
Assignment
Parallel Assignment
Trial Arms
3