Study to Gather Information About Proper Dosing and Safety of the Oral FXIa Inhibitor BAY 2433334 in Patients Following a Recent Non Cardioembolic Ischemic Stroke Which Occurs When a Blood Clot Has Formed Somewhere in the Human Body (But Not in the Heart) Travelled to the Brain. (PACIFIC-STROKE)

Multicenter, Randomized, Placebo-controlled, Double-blind, Parallel Group, Dose-finding Phase 2 Study to Evaluate Efficacy and Safety of BAY2433334 in Patients Following an Acute Non-cardioembolic Ischemic Stroke

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 on top of antiplatelet therapy in patients following a recent non cardioembolic ischemic stroke which occurs when a blood clot that has not formed in the heart travelled to the brain. 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.

Study Overview

• Status: Completed
• Conditions: Acute Non-cardioembolic Ischemic Stroke
• Intervention / Treatment: Drug: BAY2433334; Other: BAY2433334 matching placebo

• Study Type: Interventional
• Enrollment (Actual): 1808
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital
    • New Lambton, New South Wales, Australia, 2305
      • John Hunter Hospital
    • Sydney, New South Wales, Australia, 2065
      • Royal North Shore Hospital
  • Queensland
    • Birtinya, Queensland, Australia, 4575
      • Sunshine Coast University Hospital
    • Southport, Queensland, Australia, 4215
      • Gold Coast University Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Ballarat, Victoria, Australia, 3350
      • Grampians Health Ballarat
    • Box Hill, Victoria, Australia, 3128
      • Eastern Clinical Research Unit - Box Hill
    • Parkville, Victoria, Australia, 3052
      • Royal Melbourne Hospital
    • Prahran, Victoria, Australia, 3004
      • The Alfred Hospital
  • Western Australia
    • Murdoch, Western Australia, Australia, 6961
      • Fiona Stanley Hospital
• Austria
  • Salzburg, Austria, 5020
    • Christian-Doppler-Klinik
  • Wien, Austria, 1020
    • Krankenhaus der Barmherzigen Brüder
  • Wien, Austria, 1090
    • Universitätsklinikum AKH Wien
  • Wien, Austria, 1100
    • Klinik Favoriten - Sozialmedizinisches Zentrum Süd
  • Burgenland
    • Eisenstadt, Burgenland, Austria, 7000
      • Krankenhaus der Barmherzigen Brüder Eisenstadt
  • Oberösterreich
    • Linz, Oberösterreich, Austria, 4021
      • Konventhospital Barmherzige Brüder Linz
  • Tirol
    • Innsbruck, Tirol, Austria, 6020
      • Medizinische Universität Innsbruck
• Belgium
  • Brasschaat, Belgium, 2930
    • AZ Klina / Neurology
  • Brussel, Belgium, 1090
    • UZ Brussel
  • Leuven, Belgium, 3000
    • UZ Leuven Gasthuisberg
  • Oostende, Belgium, 8400
    • Kust, Ommeland en Meetjesland (KOM) Network | AZ Damiaan - Neurology Department
  • Roeselare, Belgium, 8800
    • AZ Delta / Neurology
  • Uccle, Belgium, 1180
    • Clinique de l'Europe
  • Limburg
    • Hasselt, Limburg, Belgium, 3500
      • Jessa Ziekenhuis
  • Liège
    • Liege, Liège, Belgium, 4000
      • Chc Montlegia
• Bulgaria
  • Haskovo, Bulgaria, 6300
    • MHAT Haskovo
  • Pleven, Bulgaria, 5809
    • UMHAT Dr. Georgi Stranski
  • Plovdiv, Bulgaria, 4000
    • MHAT Sveti Pantaleymon - Plovdiv
  • Ruse, Bulgaria, 7002
    • UMHAT Kanev AD
  • Sofia, Bulgaria, 1000
    • First Multiprofile Hospital for Active Treatment Sofia EAD
  • Sofia, Bulgaria, 1309
    • MHAT National Cardiology Hospital EAD
  • Sofia, Bulgaria, 1407
    • Acibadem City Clinic Multiprofile Hospital for Active Treatm
  • Sofia, Bulgaria, 1606
    • UMHATEM N. I. Pirogov EAD
  • Sofia, Bulgaria, 1750
    • UMHAT "Sveta Anna"-Sofia
  • Varna, Bulgaria, 9010
    • MHAT Sveta Marina EAD
• China
  • Shanghai, China, 200040
    • Huashan Hospital, Fudan University
  • Tianjin, China, 300350
    • Tianjin Huanhu Hospital
  • Heilongjiang
    • Daqing, Heilongjiang, China, 163000
      • Daqing Oilfield General Hospital
  • Inner Mongolia
    • Baotou, Inner Mongolia, China, 014010
      • Baogang hospital
  • Jiangsu
    • Nanjing, Jiangsu, China, 210006
      • Nanjing First Hospital
    • Nanjing, Jiangsu, China, 210009
      • Zhongda Hospital Southeast University
  • Jilin
    • Changchun, Jilin, China, 130000
      • The first hospital of Jilin University
  • Sichuan
    • Deyang, Sichuan, China, 618099
      • People's Hospital Of DeYang City
• Czechia
  • Brno, Czechia, 656 91
    • Fakultni nemocnice u sv. Anny
  • Ceske Budejovice, Czechia, 370 01
    • Nemocnice Ceske Budejovice, a.s. Department of kardiologie
  • Hradec Kralove, Czechia, 500 05
    • Fakultni nemocnice Hradec Kralove
  • Jihlava, Czechia, 58633
    • Hospital Jihlava - Nemocnice Jihlava
  • Ostrava Vitkovice, Czechia, 70384
    • Vitkovicka nemocnice a.s.
  • Ostrava-Poruba, Czechia, 708 52
    • Fakultni nemocnice Ostrava
  • Pardubice, Czechia, 530 03
    • Nemocnice Pardubickeho kraje, a.s., Pardubicka nemocnice
  • Praha 10, Czechia, 10034
    • Fakultni nemocnice Kralovske Vinohrady
  • Praha 5-Motol, Czechia, 150 00
    • Nemocnice na Homolce - Neurology Department
• Denmark
  • Aalborg, Denmark, 9100
    • Aalborg Universitetshospital -Neurology
  • Aarhus N, Denmark, 8200
    • Aarhus Universitetshospital, Skejby
  • Copenhagen, Denmark, 2400
    • Bispebjerg Hospital
  • Glostrup, Denmark, 2600
    • Rigshospitalet Glostrup
  • Herlev, Denmark, 2730
    • Herlev Hospital - Neurology Dept.
  • Herning, Denmark, 7400
    • Regionshospitalet Gødstrup
  • Hillerød, Denmark, DK-3400
    • Nordsjælland Hospital Hillerød
  • Kolding, Denmark, 6000
    • Sygehus Lillebaelt | Kolding Sygehus - Medicinske Sygdomme
• Finland
  • Helsinki, Finland, 00029
    • HUS, Meilahden sairaala
  • Kuopio, Finland, 70210
    • Itä-Suomen yliopisto
  • Turku, Finland, FIN-20520
    • Turun yliopistollinen keskussairaala
• France
  • Besancon, France, 25030
    • Hôpital Jean Minjoz
  • Bordeaux, France, 33000
    • Hôpital Pellegrin - Bordeaux
  • Le Kremlin-bicetre, France, 94275
    • Centre Hospitalier Universitaire - Le Kremlin Bicêtre
  • Le Mans, France, 72037
    • Centre Hospitalier - Le Mans
  • Lille, France, 59037
    • Hôpital B - Lille
  • Nancy, France, 54037
    • Hopital Central - Nancy
  • PARIS cedex 14, France, 75674
    • Centre hospitalier Sainte Anne
  • Paris, France, 75475
    • Hôpital Lariboisière - Paris
  • Paris, France, 75634
    • Hôpital de la Pitié-Salpêtrière
  • Rennes Cedex, France, 35033
    • Hôpital Pontchaillou
  • Toulouse, France, 31059
    • Hôpital Purpan - Toulouse
• Germany
  • Baden-Württemberg
    • Heidelberg, Baden-Württemberg, Germany, 69120
      • Universitätsklinikum Heidelberg
    • Tübingen, Baden-Württemberg, Germany, 72076
      • Eberhard-Karls-Universität Tübingen
    • Ulm, Baden-Württemberg, Germany, 89081
      • Universitätsklinikum Ulm
  • Bayern
    • Bad Neustadt, Bayern, Germany, 97616
      • Rhön-Klinikum Campus Bad Neustadt
  • Hessen
    • Frankfurt, Hessen, Germany, 60528
      • Universitätsklinikum der Johann Wolfgang Goethe Universität
    • Frankfurt, Hessen, Germany, 65929
      • Klinikum Frankfurt Höchst GmbH
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30625
      • Medizinische Hochschule Hannover (MHH)
  • Nordrhein-Westfalen
    • Düsseldorf, Nordrhein-Westfalen, Germany, 40225
      • Heinrich-Heine-Universität Düsseldorf
    • Essen, Nordrhein-Westfalen, Germany, 45131
      • Alfried Krupp Krankenhaus Rüttenscheid /Neurologie
  • Sachsen
    • Leipzig, Sachsen, Germany, 04103
      • Universitätsklinikum Leipzig AöR
  • Thüringen
    • Altenburg, Thüringen, Germany, 04600
      • Klinikum Altenburger Land GmbH
• Hungary
  • Budapest, Hungary, 1134
    • Eszak-Pesti Centrumkorhaz-Honvedkorhaz
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Klinikai Kozpont
  • Kistarcsa, Hungary, 2143
    • Flor Ferenc Korhaz
  • Pecs, Hungary, 7624
    • Pecsi Tudomanyegyetem Klinikai Kozpont
  • Szeged, Hungary, 6725
    • SZTE ÁOK Szent Györgyi Albert Klinikai Kozpont
  • Zalaegerszeg, Hungary, 8900
    • Zala Megyei Szent Rafael Kórház
• Italy
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40133
      • AUSL di Bologna
    • Forlì Cesena, Emilia-Romagna, Italy, 47521
      • AUSL della Romagna
    • Reggio Emilia, Emilia-Romagna, Italy, 42123
      • AUSL-IRCCS di Reggio Emilia
  • Lazio
    • Roma, Lazio, Italy, 00152
      • A.O. San Camillo-Forlanini
  • Lombardia
    • Milano, Lombardia, Italy, 20132
      • Ospedale San Raffaele s.r.l.
    • Pavia, Lombardia, Italy, 27100
      • Fondazione Istituto Neurologico Nazionale Casimiro Mondino
  • Marche
    • Ancona, Marche, Italy, 60126
      • A.O.U. Ospedali Riuniti "Umberto I - G.M.Lancisi - G.Salesi"
  • Toscana
    • Siena, Toscana, Italy, 53100
      • A.O.U. Senese
  • Umbria
    • Perugia, Umbria, Italy, 06129
      • A.O. di Perugia
• Japan
  • Fukuoka, Japan, 810-8563
    • National Hospital Organization Kyushu Medical Center
  • Fukuoka, Japan, 810-0001
    • Saiseikai Fukuoka General Hospital
  • Gifu, Japan, 500-8717
    • Gifu Prefectural General Medical Center
  • Hiroshima, Japan, 730-8518
    • Hiroshima City Hiroshima Citizens Hospital
  • Kochi, Japan, 780-8522
    • Chikamori Hospital
  • Kumamoto, Japan, 861-4193
    • Saiseikai Kumamoto Hospital
  • Kumamoto, Japan, 861-8520
    • Japanese Red Cross Kumamoto Hospital
  • Kyoto, Japan, 601-1495
    • Ijinkai Takeda General Hospital
  • Nagano, Japan, 381-8551
    • Nagano Municipal Hospital
  • Aichi
    • Nagoya, Aichi, Japan, 454-8502
      • Nagoya Ekisaikai Hospital
  • Fukuoka
    • Kitakyushu, Fukuoka, Japan, 802-8555
      • Kokura Memorial Hospital
    • Kurume, Fukuoka, Japan, 830-8543
      • St.Mary's Hospital
  • Fukushima
    • Koriyama, Fukushima, Japan, 963-8563
      • Southern Tohoku Medical Clinic
  • Hokkaido
    • Hakodate, Hokkaido, Japan, 041-0802
      • Hakodate Shintoshi Hospital
  • Hyogo
    • Himeji, Hyogo, Japan, 670-8560
      • Hyogo Prefectural Harima-Himeji General Medical Center
    • Kobe, Hyogo, Japan, 650-0047
      • Kobe City Medical Center General Hospital
  • Ibaraki
    • Toride, Ibaraki, Japan, 302-0022
      • JA Toride Medical Center
  • Kanagawa
    • Kamakura, Kanagawa, Japan, 247-8533
      • Shonan Kamakura General Hospital
  • Kyoto
    • Kusegun, Kyoto, Japan, 613-0034
      • Kyoto Okamoto Memorial Hospital
    • Uji, Kyoto, Japan, 611-0041
      • Uji-Tokushukai Medical Center
  • Osaka
    • Daito, Osaka, Japan, 574-0074
      • Nozaki Tokushukai Hospital
  • Tokyo
    • Mitaka, Tokyo, Japan, 181-8611
      • Kyorin University Hospital
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academisch Medisch Centrum (AMC)
  • Heerlen, Netherlands, 6419 PC
    • Zuyderland Medisch Centrum
  • Nieuwegein, Netherlands, 3435 CM
    • St. Antonius Ziekenhuis
  • Zwolle, Netherlands, 8025 AB
    • Isala
• Poland
  • Gdansk, Poland, 80-803
    • Copernicus PL, M.Kopernik Hospital
  • Grodzisk Mazowiecki, Poland, 05-825
    • Samodzielny Publiczny Specjalistyczny Szpital Zachodni
  • Katowice, Poland, 40-635
    • Gornoslaskie CM im. Prof. Leszka Gieca SUM w Katowicach
  • Krakow, Poland, 30-688
    • Szpital Uniwersytecki w Krakowie
  • Lublin, Poland, 20-090
    • Samodzielny Publiczny Szpital Kliniczny nr 4
  • Ostroleka, Poland, 07-410
    • Mazowiecki Szpital Specjalistyczny im. dr. Jozefa Psarskiego
  • Warszawa, Poland, 04-141
    • Wojskowy Instytut Medyczny
• Portugal
  • Coimbra, Portugal, 3004-561
    • CHUC - Hospitais da U. Coimbra - Servico de Neurologia
  • Lisboa, Portugal, 1349-019
    • CHLO - Hospital Egas Moniz
  • Lisboa, Portugal, 1500-650
    • Hospital da Luz - Lisboa
  • Lisboa, Portugal, 1649-035
    • CHULN - Hospital Santa Maria
  • Porto, Portugal, 4200-319
    • CHUSJ - Hospital Sao Joao
  • Lisboa
    • Loures, Lisboa, Portugal, 2674-514
      • Luz Saude | Hospital Beatriz Angelo - Centro de Investigacao Clinica
  • Porto
    • Matosinhos, Porto, Portugal, 4464-513
      • ULSM - Hospital Pedro Hispano
  • Setúbal
    • Almada, Setúbal, Portugal, 2801-951
      • Hospital Garcia de Orta | Research Department
• Russian Federation
  • Chelyabinsk, Russian Federation, 454021
    • City Clinical Hospital #3
  • Kemerovo, Russian Federation, 650002
    • Sci-Res. Institute of Complex Cardiovascular Disorders
  • Krasnodar, Russian Federation, 350086
    • Regional Clinical Hospital #1 n.a. prof. S.V. Ochapovsky
  • Novosibirsk, Russian Federation, 630003
    • Railway clinical hospital on the station Novosibirsk-Glavniy
  • Sestroretsk, Russian Federation, 197706
    • City clinical hospital #40 Sestroretsk
  • Tomsk, Russian Federation, 634063
    • Tomsk Regional Clinical Hospital
  • Vsevolozhsk, Russian Federation, 188643
    • Clinical Inter-District Hospital of Vsevolozhsk
  • Yekaterinburg, Russian Federation, 620102
    • Sverdlovsk Regional Clinical Hospital #1
• Slovakia
  • Bratislava, Slovakia, 813 69
    • Univerzitna nemocnica Bratislava, Nemocnica Stare Mesto
  • Dolny Kubin, Slovakia, 026 14
    • Dolnooravska nemocnica s poliklinikou L. Nadasi Jegeho
  • Levoca, Slovakia, 054 01
    • Vseobecna nemocnica s poliklinikou Levoca, a.s.
  • Liptovsky Mikulas, Slovakia, 031 023
    • Liptovska Nemocnica S Poliklinikou Mudr. Ivana Stodolu
  • Rimavska Sobota, Slovakia, 979 12
    • Svet zdravia, a. s. Vseobecna nemocnica Rimavska Sobota
  • Skalica, Slovakia, 909 82
    • Fakultna nemocnica AGEL Skalica, a.s.
  • Spisska Nova Ves, Slovakia, 05201
    • Svet zdravia, a.s. Nemocnica s poliklinikou Spisska Nova Ves
  • Trnava, Slovakia, 917 75
    • Fakultna nemocnica Trnava
  • Ziar nad Hronom, Slovakia, 965 37
    • Vseobecna nemocnica v Ziari nad Hronom
• Spain
  • Albacete, Spain, 02006
    • Complejo Hospitalario Universitario de Albacete | Hospital General Universitario - Neurology Department, Stroke Unit
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08023
    • Ciutat Sanitaria i Universitaria de la Vall d'Hebron
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau | Neurology Department - Stroke, No-Cardioembolic-Tia
  • Lleida, Spain, 25198
    • Hospital Universitario Arnau de Vilanova de Lleida
  • Madrid, Spain, 28006
    • Hospital Universitario de La Princesa
  • Madrid, Spain, 28040
    • Hospital Clinico Universitario San Carlos | Neurologia
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal | Neurology Department - Stroke, No-Cardioembolic-Tia
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen Del Rocio
  • Valencia, Spain, 46026
    • La Fe University and Polytechnic Hospital | Neurology Service - Vascular Unit
  • Valladolid, Spain, 47003
    • Hospital Universitario Clinico de Valladolid | Neurology Department
  • A Coruña
    • Santiago de Compostela, A Coruña, Spain, 15706
      • Hospital Clínico Universitario de Santiago de Compostela
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol
    • Terrassa, Barcelona, Spain, 8221
      • Hospital de la Mútua de Terrassa
  • Madrid
    • Móstoles, Madrid, Spain, 28933
      • Hospital Rey Juan Carlos
• Sweden
  • Lund, Sweden, 221 85
    • Skanes universitetssjukhus
  • Stockholm, Sweden, 182 88
    • Danderyds Sjukhus
  • Umeå, Sweden, 901 85
    • Norrlands Universitetssjukhus, Umea
• Switzerland
  • Baden, Switzerland, 5404
    • Kantonsspital Baden
  • Bern, Switzerland, 3010
    • Inselspital Universitätsspital Bern
  • Lugano, Switzerland, 6900
    • Ospedale Regionale di Lugano
  • Basel-Stadt
    • Basel, Basel-Stadt, Switzerland, 4031
      • Universitätsspital Basel
  • Bern
    • Biel, Bern, Switzerland, 2501
      • Spitalzentrum Biel
  • Sankt Gallen
    • St. Gallen, Sankt Gallen, Switzerland, 9007
      • Kantonsspital St. Gallen
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrookes Hospital
  • Coventry, United Kingdom, CV2 2DX
    • University Hospitals Coventry and Warwickshire NHS Trust
  • Glasgow, United Kingdom, G51 4TF
    • Queen Elizabeth University Hospital
  • Glasgow, United Kingdom, G4 0SF
    • Glasgow Royal Infirmary | Glasgow Clinical Research Facility
  • London, United Kingdom, SW17 0QT
    • St George's Hospital
  • London, United Kingdom, W6 8RF
    • Charing Cross Hospital
  • Cheshire
    • Chester, Cheshire, United Kingdom, CH2 1UL
      • Countess of Chester Hospital
  • Merseyside
    • Wirral, Merseyside, United Kingdom, CH49 5PE
      • Arrowe Park Hospital
  • Tyne And Wear
    • Newcastle Upon Tyne, Tyne And Wear, United Kingdom, NE1 4LP
      • Royal Victoria Infirmary
• United States
  • Florida
    • Tampa, Florida, United States, 33606
      • Univ.of South Florida College of Medicine
  • Minnesota
    • Golden Valley, Minnesota, United States, 55422
      • Minneapolis Clinic of Neurology, Ltd.
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • St. Luke's Hospital of Kansas City
  • North Carolina
    • Greensboro, North Carolina, United States, 27405
      • Guilford Neurologic Associates
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16550
      • University of Pittsburgh Medical Center Hamot

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant must be 45 years of age and older at the time of signing the informed consent

• Non-cardioembolic ischemic stroke with

  • persistent signs and symptoms of stroke lasting for ≥ 24 hours OR
  • acute brain infarction documented by computed tomography (CT) or MRI AND
  • with the intention to be treated with antiplatelet therapy during the study conduct
• Imaging of brain (CT or MRI) ruling out hemorrhagic stroke or another pathology that could explain symptoms (e.g. brain tumor, abscess, vascular malformation)

• Severity of index event nearest the time of randomization:

  • Part A: minor stroke (defined as National Institutes of Health Stroke Scale (NIHSS) ≤ 7) can be enrolled
  • Part B: participants with minor or moderate stroke and NIHSS ≤ 15 can be enrolled. Participants undergoing thrombolysis or endovascular therapy (mechanical thrombectomy) can be enrolled but at the earliest 24 hours after the intervention
• Randomization within 48 hours after the onset of symptoms of the index event (or after patients were last known to be without symptoms in case of wake-up stroke)
• Ability to conduct an MRI either before randomization or within 72 hours after randomization

Exclusion Criteria:

• Prior ischemic stroke within last 30 days of index event
• History of atrial fibrillation or suspicion of cardioembolic source of stroke
• Dysphagia with inability to safely swallow study medication
• Contraindication to perform brain MRI
• Part A only: thrombolysis or endovascular therapy (mechanical thrombectomy) performed for index event
• Active bleeding; known bleeding disorder, history of major bleeding (intracranial, retroperitoneal, intraocular) or clinically significant gastrointestinal bleeding within last 6 months of randomization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BAY2433334 high dose	Drug: BAY2433334; Tablet, taken orally once a day.
Experimental: BAY2433334 medium dose	Drug: BAY2433334; Tablet, taken orally once a day.
Experimental: BAY2433334 low dose	Drug: BAY2433334; Tablet, taken orally once a day.
Placebo Comparator: BAY2433334 matching placebo	Other: BAY2433334 matching placebo; Tablet, taken orally once a day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy-Number of Participants With Composite of Symptomatic Ischemic Stroke or Covert Brain Infarcts Detected by Magnetic Resonance Imaging (MRI)	Ischemic stroke was defined as either of : 1) Rapid onset (or present on awakening) of a new focal neurological deficit with clinical (>24 hours symptoms/signs) or imaging evidence of infarction that was not attributable to a non-ischemic cause; 2) Acute worsening of an existing focal neurological deficit that was judged to be attributable to a new infarction or extension of the previous infarction in the same vascular territory, based on persisting symptoms/signs or imaging evidence of infarction and no evidence of a non-ischemic etiology. If imaging was inconclusive, persistent symptoms/signs must be significant (worsening of NIHSS score of 4 or more) and sustained (duration of ≥24 hours or until death). Covert brain infarcts were defined as incident infarcts detected by serial MRI in the absence of an adjudicated stroke consistent with the location of the infarct. MRI criteria for brain infarction were available in the MRI procedures manual.	From baseline up to 26 weeks
Safety-Number of Participants With Composite of International Society on Thrombosis and Hemostasis (ISTH) Major Bleeding and 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.	From baseline up to 52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy-Number of Participants With Composite of Symptomatic Ischemic Stroke and Covert Brain Infarcts Detected by MRI, Cardiovascular (CV) Death, Myocardial Infarction (MI) and Systemic Embolism.	CV death included death due to stroke, MI, heart failure or cardiogenic shock, sudden death or any other death due to other cardiovascular causes. Death due to non-traumatic hemorrhage was included. Acute MI was used when there was evidence of myocardial necrosis in a clinical setting consistent with acute myocardial ischemia. According to MI Universal Definition from 2018 the diagnosis of MI required the combination of: 1) Presence of acute myocardial injury, and 2) Evidence of acute myocardial ischemia derived from the clinical presentation, electrocardiographic changes, or the results of myocardial or coronary artery imaging, or in case of post-mortem pathological findings irrespective of biomarker values. Systemic embolism was defined as abrupt vascular insufficiency associated with clinical or radiological evidence of arterial occlusion in the absence of other likely mechanisms (this did not include thromboembolism of the pulmonary vasculature or venous thrombosis).	From baseline up to 26 weeks
Efficacy-Number of Participants With Symptomatic Ischemic Stroke	Definition of symptomatic ischemic stroke can be referred to first Primary endpoint.	From baseline up to 52 weeks
Efficacy-Number of Participants With Covert Brain Infarcts Detected by MRI	Definition of covert brain infarcts can be referred to first Primary endpoint.	From baseline up to 26 weeks
Efficacy-Number of Participants With Symptomatic Ischemic Stroke, CV Death, MI	Definition of symptomatic ischemic stroke can be referred to first Primary endpoint. Definition of CV death and MI can be referred to first Second endpoint.	From baseline up to 52 weeks
Efficacy-Number of Participants With Symptomatic Ischemic and Hemorrhagic Stroke	Definition of symptomatic ischemic can be referred to fourth secondary endpoint. Hemorrhagic stroke was defined as an acute, atraumatic extravasation of blood into the brain parenchyma, intraventricular or subarachnoid space with associated neurological symptoms. This did not include microbleeds or hemorrhagic transformation of an ischemic stroke.	From baseline up to 52 weeks
Efficacy-Number of Participants With Disabling Stroke (mRS≥4)	Modified ranking score (mRS): 0-No symptoms at all; 1-No significant disability despite symptoms; despite symptoms, able to carry out all usual duties and activities; 2-Slight disability; unable to carry out all previous activities but able to look after own affairs without assistance; 3-Moderate disability; requiring some help, but able to walk without assistance; 4-Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance; 5-Severe disability; bedridden, incontinent and requiring constant nursing care and attention; 6-Death.	From baseline up to 52 weeks
Efficacy-Number of Participants With All-cause Mortality		From baseline up to 52 weeks
Safety-Number of Participants With All Bleeding	All bleeding events occurred from first intake of study intervention until 2 days after the last intake of study intervention.	From baseline up to 52 weeks
Safety-Number of Participants With ISTH Major Bleeding	Definition of ISTH major bleeding can be referred to second Primary endpoint.	From baseline up to 52 weeks
Safety-Number of Participants With ISTH CRNM Bleeding	Definition of ISTH CRNM bleeding can be referred to second Primary endpoint.	From baseline up to 52 weeks
Safety-Number of Participants With ISTH Minor Bleeding	All other overt bleeding episodes not meeting the above criteria for ISTH major or CRNM bleeding were classified as minor bleeding (e.g. bleeding from a minor wound that does not prompt a face-to-face evaluation for a physical examination or laboratory testing).	From baseline up to 52 weeks
Safety-Number of Participants With Intracerebral Hemorrhage (Non-traumatic)	Non-traumatic intracerebral hemorrhage was defined as a hemorrhagic stroke on the "recurrent stroke" CRF page that is in addition classified as a bleeding with bleeding site intracranial (-subarachnoid, -intraparenchymal [excluding microbleeds], or -intraventricular) and spontaneous causality of bleeding, excluding all symptomatic and hemorrhagic transformation (defined by the PT "hemorrhagic transformation").	From baseline up to 52 weeks

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Population Health Research Institute

Publications and helpful links

General Publications

• Shoamanesh A, Mundl H, Smith EE, Masjuan J, Milanov I, Hirano T, Agafina A, Campbell B, Caso V, Mas JL, Dong Q, Turcani P, Christensen H, Ferro JM, Veltkamp R, Mikulik R, De Marchis GM, Robinson T, Lemmens R, Stepien A, Greisenegger S, Roine R, Csiba L, Khatri P, Coutinho J, Lindgren AG, Demchuk AM, Colorado P, Kirsch B, Neumann C, Heenan L, Xu L, Connolly SJ, Hart RG; PACIFIC-Stroke Investigators. Factor XIa inhibition with asundexian after acute non-cardioembolic ischaemic stroke (PACIFIC-Stroke): an international, randomised, double-blind, placebo-controlled, phase 2b trial. Lancet. 2022 Sep 24;400(10357):997-1007. doi: 10.1016/S0140-6736(22)01588-4. Epub 2022 Sep 2.

Helpful Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe.
• Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2020
• Primary Completion (Actual): February 18, 2022
• Study Completion (Actual): February 18, 2022

Study Registration Dates

• First Submitted: March 8, 2020
• First Submitted That Met QC Criteria: March 8, 2020
• First Posted (Actual): March 11, 2020

Study Record Updates

• Last Update Posted (Actual): April 19, 2023
• Last Update Submitted That Met QC Criteria: April 17, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction
• Other Study ID Numbers: 19766; 2019-003431-33 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

Availability of this study's data will be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access.

As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No