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.

Atrial Fibrillation (AF) Clinical Trial

— PACIFIC-AF  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04218266
• Other study ID #: 19765
• Secondary ID: 2019-002365-35
• Status: Completed
• Phase: Phase 2
• Start date: January 30, 2020
• Est. completion date: October 8, 2021

Study information

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

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 755
• Est. completion date: October 8, 2021
• Est. primary completion date: October 8, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation
• Atrial Fibrillation (AF)

Intervention

Drug:
• BAY2433334
Tablet, taken orally once a day.
• Apixaban
Capsule, taken orally twice a day.

Other:
• BAY2433334 matching placebo
Tablet, taken orally once a day.
• Apixaban matching placebo
Capsule, taken orally twice a day.

Locations

Country	Name	City	State
Austria	Krankenhaus St. Josef Braunau	Braunau	Oberösterreich
Austria	Landeskrankenhaus Feldkirch	Feldkirch	Vorarlberg
Austria	Medizinische Universität Graz	Graz	Steiermark
Austria	Medizinische Universität Innsbruck	Innsbruck	Tirol
Austria	Ordensklinikum Linz GmbH Elisabethinen	Linz	Oberösterreich
Austria	Uniklinikum Salzburg - Landeskrankenhaus	Salzburg
Austria	Klinik Floridsdorf - Krankenhaus Nord	Wien
Austria	Universitätsklinikum AKH Wien	Wien
Belgium	Imeldaziekenhuis - St-Elisabethkliniek	Bonheiden
Belgium	AZ St-Jan Brugge Oostende AV	Brugge
Belgium	UZ Antwerpen	Edegem
Belgium	Jessa Ziekenhuis	Hasselt
Belgium	UZ Leuven Gasthuisberg	Leuven	Vlaams Brabant
Belgium	VZW Emmaus	Mechelen
Belgium	AZ Delta	Roeselare
Canada	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia
Canada	Clinique Sante Cardio MC	Montreal	Quebec
Canada	Montreal Heart Institute	Montreal	Quebec
Canada	Institut universitaire de cardiologie et de pneumologie	Ste-Foy	Quebec
Czechia	Fakultni nemocnice Plzen - Lochotin	Plzen
Czechia	Fakultni nemocnice Kralovske Vinohrady	Praha 10
Czechia	Institut Klinicke a Experimentalni Mediciny	Praha 4
Czechia	Fakultni nemocnice v Motole	Praha 5
Czechia	Nemocnice Slany	Slany
Czechia	Krajska nemocnice T. Bati, a.s.	Zlin
France	Hôpital Henri Mondor	Creteil
France	Centre Hospitalier Départemental Vendée	La Roche Sur Yon Cedex
France	Centre Hospitalier Louis Pasteur	Le Coudray
France	Hopital Bichat - Paris	Paris
France	Centre Hospitalier Régional - Saint Brieuc	Saint Brieuc
France	Hôpital de Rangueil - Toulouse	Toulouse
France	Centre Hospitalier - Valenciennes Cedex	Valenciennes Cedex
Hungary	Tagore Medical Center	Balatonfured
Hungary	Magyar Honvedseg Egeszsegugyi Kozpont	Budapest
Hungary	University of Semmelweis/ Semmelweis Egyetem	Budapest
Hungary	Kanizsai Dorottya Hospital	Nagykanizsa
Hungary	Medifarma-98 Egeszsegugyi, Kereskedelmi es Szolgaltato Kft.	Nyiregyhaza
Hungary	Pecsi Tudomanyegyetem Klinikai Kozpont	Pecs
Hungary	Tolna Megyei Balassa Janos Korhaz	Szekszard
Hungary	Csongrad-Csanad Megyei Dr. Bugyi Istvan Korhaz	Szentes
Italy	AUSL Toscana Sud-Est	Arezzo	Toscana
Italy	AUSL Toscana Sud-Est	Arezzo	Toscana
Italy	ASUR Marche - Area Vasta 5	Ascoli Piceno	Marche
Italy	ASST Spedali Civili di Brescia	Brescia	Lombardia
Italy	IRCCS Ospedale Policlinico San Martino	Genova	Liguria
Italy	A.O. di Perugia	Perugia	Umbria
Italy	A.O.U. Policlinico Umberto I	Roma	Lazio
Japan	Nishiarai Heart Central Clinic	Adachi-ku	Tokyo
Japan	Minamino Cardiovascular Hospital	Hachioji	Tokyo
Japan	Tokyo Angel Hospital	Hachioji	Tokyo
Japan	Hyogo Prefectural Harima-Himeji General Medical Center	Himeji	Hyogo
Japan	Nakamura Cardiovascular Clinic	Itoshima	Fukuoka
Japan	Kishiwada Tokushukai Hospital	Kishiwada	Osaka
Japan	Koto Hospital	Koto-ku	Tokyo
Japan	Hayama Heart Center	Miura-gun	Kanagawa
Japan	Yao Tokushukai General Hospital	Yao	Osaka
Latvia	Daugavpils Regional Hospital	Daugavpils
Latvia	Doctor's Practice in Cardiology	Daugavpils
Latvia	Liepaja Regional Hospital	Liepaja
Latvia	1st Riga Clinical Hospital	Riga
Latvia	P. Stradins Clinical University Hospital	Riga
Latvia	Riga East Clinical University Hospital "Gailezers"	Riga
Netherlands	Academisch Medisch Centrum (AMC)	Amsterdam
Netherlands	Ziekenhuis Rijnstate	Arnhem
Netherlands	Amphia Ziekenhuis, locatie Molengracht	Breda
Netherlands	Albert Schweitzer Ziekenhuis, Dordwijk	Dordrecht
Netherlands	Medisch Spectrum Twente	Enschede
Netherlands	Martini Ziekenhuis, Locatie van Swieten	Groningen
Netherlands	Spaarne Gasthuis - locatie Zuid	Haarlem
Netherlands	Maastricht UMC	Maastricht
Spain	Ciutat Sanitària i Universitaria de la Vall d'Hebron	Barcelona
Spain	Hospital de la Santa Creu i de Sant Pau | Cardiología	Barcelona
Spain	Ciutat Sanitària i Universitària de Bellvitge	L'Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Virgen de la Victoria	Málaga
Sweden	Falu Lasarett	Falun
Sweden	Clemenstorget Hjärtmottagning	Lund
Sweden	Avdelningen för kliniska prövningar AKP	Örebro
Sweden	Östersunds Sjukhus	Östersund
Sweden	Skellefteå Lasarett	Skellefteå
Sweden	Danderyds sjukhus	Stockholm
Sweden	Södersjukhuset AB	Stockholm
Switzerland	Kantonsspital Aarau	Aarau	Aargau
Switzerland	Universitätsspital Basel	Basel	Basel-Stadt
Switzerland	Inselspital Universitätsspital Bern	Bern
Switzerland	Hôpital Cantonal Universitaire de Genève	Genève
Switzerland	Ospedale regionale di Lugano	Lugano
Switzerland	Kantonsspital St. Gallen	St. Gallen	Sankt Gallen
United Kingdom	St Richard's Hospital	Chichester	West Sussex
United Kingdom	Staploe Medical Centre	Ely	Cambridgeshire
United Kingdom	Northwick Park Hospital	Harrow	London
United Kingdom	Heart and Chest Hospital	Liverpool
United Kingdom	Queen Elizabeth II Hospital	Welwyn Garden City	Hertfordshire

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

Austria,  Belgium,  Canada,  Czechia,  France,  Hungary,  Italy,  Japan,  Latvia,  Netherlands,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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	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).	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	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.	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	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.	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	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.	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)

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