Clinical trial NCT04304508: 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.
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Non-cardioembolic Ischemic Stroke
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Population Health Research Institute
First posted: 2020-03-11
Enrollment: 1808
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 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Efficacy-Number of Participants With Composite of Symptomatic Ischemic Stroke or Covert Brain Infarcts Detected by Magnetic Resonance Imaging (MRI)
timeFrame: From baseline up to 26 weeks
measure: Safety-Number of Participants With Composite of International Society on Thrombosis and Hemostasis (ISTH) Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding
timeFrame: From baseline up to 52 weeks
Secondary outcomes:
measure: 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.
timeFrame: From baseline up to 26 weeks
measure: Efficacy-Number of Participants With Symptomatic Ischemic Stroke
timeFrame: From baseline up to 52 weeks
measure: Efficacy-Number of Participants With Covert Brain Infarcts Detected by MRI
timeFrame: From baseline up to 26 weeks
measure: Efficacy-Number of Participants With Symptomatic Ischemic Stroke, CV Death, MI
timeFrame: From baseline up to 52 weeks
measure: Efficacy-Number of Participants With Symptomatic Ischemic and Hemorrhagic Stroke
timeFrame: From baseline up to 52 weeks
measure: Efficacy-Number of Participants With Disabling Stroke (mRS≥4)
timeFrame: From baseline up to 52 weeks
measure: Efficacy-Number of Participants With All-cause Mortality
timeFrame: From baseline up to 52 weeks
measure: Safety-Number of Participants With All Bleeding
timeFrame: From baseline up to 52 weeks
measure: Safety-Number of Participants With ISTH Major Bleeding
timeFrame: From baseline up to 52 weeks
measure: Safety-Number of Participants With ISTH CRNM Bleeding
timeFrame: From baseline up to 52 weeks
measure: Safety-Number of Participants With ISTH Minor Bleeding
timeFrame: From baseline up to 52 weeks
measure: Safety-Number of Participants With Intracerebral Hemorrhage (Non-traumatic)
timeFrame: From baseline up to 52 weeks
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Univ.of South Florida College of Medicine
state: Florida
city: Golden Valley
country: United States
facility: Minneapolis Clinic of Neurology, Ltd.
state: Minnesota
city: Kansas City
country: United States
facility: St. Luke's Hospital of Kansas City
state: Missouri
city: Greensboro
country: United States
facility: Guilford Neurologic Associates
state: North Carolina
city: Erie
country: United States
facility: University of Pittsburgh Medical Center Hamot
state: Pennsylvania
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: New Lambton
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Birtinya
country: Australia
facility: Sunshine Coast University Hospital
state: Queensland
city: Southport
country: Australia
facility: Gold Coast University Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Ballarat
country: Australia
facility: Grampians Health Ballarat
state: Victoria
city: Box Hill
country: Australia
facility: Eastern Clinical Research Unit - Box Hill
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Prahran
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Eisenstadt
country: Austria
facility: Krankenhaus der Barmherzigen Brüder Eisenstadt
state: Burgenland
city: Linz
country: Austria
facility: Konventhospital Barmherzige Brüder Linz
state: Oberösterreich
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
state: Tirol
city: Salzburg
country: Austria
facility: Christian-Doppler-Klinik
city: Wien
country: Austria
facility: Krankenhaus der Barmherzigen Brüder
city: Wien
country: Austria
facility: Universitätsklinikum AKH Wien
city: Wien
country: Austria
facility: Klinik Favoriten - Sozialmedizinisches Zentrum Süd
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis
state: Limburg
city: Liege
country: Belgium
facility: CHC MontLégia
state: Liège
city: Brasschaat
country: Belgium
facility: AZ Klina / Neurology
city: Brussel
country: Belgium
facility: UZ Brussel
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Oostende
country: Belgium
facility: Kust, Ommeland en Meetjesland (KOM) Network | AZ Damiaan - Neurology Department
city: Roeselare
country: Belgium
facility: AZ Delta / Neurology
city: Uccle
country: Belgium
facility: Clinique de l'Europe
city: Haskovo
country: Bulgaria
facility: MHAT Haskovo
city: Pleven
country: Bulgaria
facility: UMHAT Dr. Georgi Stranski
city: Plovdiv
country: Bulgaria
facility: MHAT Sveti Pantaleymon - Plovdiv
city: Ruse
country: Bulgaria
facility: UMHAT Kanev AD
city: Sofia
country: Bulgaria
facility: First Multiprofile Hospital for Active Treatment Sofia EAD
city: Sofia
country: Bulgaria
facility: MHAT National Cardiology Hospital EAD
city: Sofia
country: Bulgaria
facility: Acibadem City Clinic Multiprofile Hospital for Active Treatm
city: Sofia
country: Bulgaria
facility: UMHATEM N. I. Pirogov EAD
city: Sofia
country: Bulgaria
facility: UMHAT "Sveta Anna"-Sofia
city: Varna
country: Bulgaria
facility: MHAT Sveta Marina EAD
city: Daqing
country: China
facility: Daqing Oilfield General Hospital
state: Heilongjiang
city: Baotou
country: China
facility: Baogang hospital
state: Inner Mongolia
city: Nanjing
country: China
facility: Nanjing First Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Zhongda Hospital Southeast University
state: Jiangsu
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Deyang
country: China
facility: People's Hospital of Deyang City
state: Sichuan
city: Shanghai
country: China
facility: Huashan Hospital, Fudan University
city: Tianjin
country: China
facility: Tianjin Huanhu Hospital
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv. Anny
city: Ceske Budejovice
country: Czechia
facility: Nemocnice Ceske Budejovice, a.s. Department of kardiologie
city: Hradec Kralove
country: Czechia
facility: Fakultni Nemocnice Hradec Kralove
city: Jihlava
country: Czechia
facility: Hospital Jihlava - Nemocnice Jihlava
city: Ostrava Vitkovice
country: Czechia
facility: Vitkovicka nemocnice a.s.
city: Ostrava-Poruba
country: Czechia
facility: Fakultni nemocnice Ostrava
city: Pardubice
country: Czechia
facility: Nemocnice Pardubickeho kraje, a.s., Pardubicka nemocnice
city: Praha 10
country: Czechia
facility: Fakultni nemocnice Kralovske Vinohrady
city: Praha 5-Motol
country: Czechia
facility: Nemocnice na Homolce - Neurology Department
city: Aalborg
country: Denmark
facility: Aalborg Universitetshospital -Neurology
city: Aarhus N
country: Denmark
facility: Aarhus Universitetshospital, Skejby
city: Copenhagen
country: Denmark
facility: Bispebjerg Hospital
city: Glostrup
country: Denmark
facility: Rigshospitalet Glostrup
city: Herlev
country: Denmark
facility: Herlev Hospital - Neurology Dept.
city: Herning
country: Denmark
facility: Regionshospitalet Gødstrup
city: Hillerød
country: Denmark
facility: Nordsjælland Hospital Hillerød
city: Kolding
country: Denmark
facility: Sygehus Lillebaelt | Kolding Sygehus - Medicinske Sygdomme
city: Helsinki
country: Finland
facility: HUS, Meilahden sairaala
city: Kuopio
country: Finland
facility: Itä-Suomen yliopisto
city: Turku
country: Finland
facility: Turun yliopistollinen keskussairaala
city: Besancon
country: France
facility: Hopital Jean Minjoz
city: Bordeaux
country: France
facility: Hôpital Pellegrin - Bordeaux
city: Le Kremlin-bicetre
country: France
facility: Centre Hospitalier Universitaire - Le Kremlin Bicêtre
city: Le Mans
country: France
facility: Centre Hospitalier - Le Mans
city: Lille
country: France
facility: Hôpital B - Lille
city: Nancy
country: France
facility: Hopital Central - Nancy
city: PARIS cedex 14
country: France
facility: Centre hospitalier Sainte Anne
city: Paris
country: France
facility: Hôpital Lariboisière - Paris
city: Paris
country: France
facility: Hôpital de la Pitié-Salpétrière
city: Rennes Cedex
country: France
facility: Hôpital Pontchaillou
city: Toulouse
country: France
facility: Hôpital Purpan - Toulouse
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
state: Baden-Württemberg
city: Tübingen
country: Germany
facility: Eberhard-Karls-Universität Tübingen
state: Baden-Württemberg
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
state: Baden-Württemberg
city: Bad Neustadt
country: Germany
facility: Rhön-Klinikum Campus Bad Neustadt
state: Bayern
city: Frankfurt
country: Germany
facility: Universitätsklinikum der Johann Wolfgang Goethe Universität
state: Hessen
city: Frankfurt
country: Germany
facility: Klinikum Frankfurt Höchst GmbH
state: Hessen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover (MHH)
state: Niedersachsen
city: Düsseldorf
country: Germany
facility: Heinrich-Heine-Universität Düsseldorf
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: Alfried Krupp Krankenhaus Rüttenscheid /Neurologie
state: Nordrhein-Westfalen
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig AöR
state: Sachsen
city: Altenburg
country: Germany
facility: Klinikum Altenburger Land GmbH
state: Thüringen
city: Budapest
country: Hungary
facility: Eszak-Pesti Centrumkorhaz-Honvedkorhaz
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Kistarcsa
country: Hungary
facility: Flor Ferenc Korhaz
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem Klinikai Kozpont
city: Szeged
country: Hungary
facility: SZTE ÁOK Szent Györgyi Albert Klinikai Kozpont
city: Zalaegerszeg
country: Hungary
facility: Zala Megyei Szent Rafael Korhaz
city: Bologna
country: Italy
facility: AUSL di Bologna
state: Emilia-Romagna
city: Forlì Cesena
country: Italy
facility: AUSL della Romagna
state: Emilia-Romagna
city: Reggio Emilia
country: Italy
facility: AUSL-IRCCS di Reggio Emilia
state: Emilia-Romagna
city: Roma
country: Italy
facility: A.O. San Camillo-Forlanini
state: Lazio
city: Milano
country: Italy
facility: Ospedale San Raffaele s.r.l.
state: Lombardia
city: Pavia
country: Italy
facility: Fondazione Istituto Neurologico Nazionale Casimiro Mondino
state: Lombardia
city: Ancona
country: Italy
facility: A.O.U. Ospedali Riuniti "Umberto I - G.M.Lancisi - G.Salesi"
state: Marche
city: Siena
country: Italy
facility: A.O.U. Senese
state: Toscana
city: Perugia
country: Italy
facility: A.O. di Perugia
state: Umbria
city: Nagoya
country: Japan
facility: Nagoya Ekisaikai Hospital
state: Aichi
city: Kitakyushu
country: Japan
facility: Kokura Memorial Hospital
state: Fukuoka
city: Kurume
country: Japan
facility: St.Mary's Hospital
state: Fukuoka
city: Koriyama
country: Japan
facility: Southern Tohoku Medical Clinic
state: Fukushima
city: Hakodate
country: Japan
facility: Hakodate Shintoshi Hospital
state: Hokkaido
city: Himeji
country: Japan
facility: Hyogo Prefectural Harima-Himeji General Medical Center
state: Hyogo
city: Kobe
country: Japan
facility: Kobe City Medical Center General Hospital
state: Hyogo
city: Toride
country: Japan
facility: JA Toride Medical Center
state: Ibaraki
city: Kamakura
country: Japan
facility: Shonan Kamakura General Hospital
state: Kanagawa
city: Kusegun
country: Japan
facility: Kyoto Okamoto Memorial Hospital
state: Kyoto
city: Uji
country: Japan
facility: Uji-Tokushukai Medical Center
state: Kyoto
city: Daito
country: Japan
facility: Nozaki Tokushukai Hospital
state: Osaka
city: Mitaka
country: Japan
facility: Kyorin University Hospital
state: Tokyo
city: Fukuoka
country: Japan
facility: Saiseikai Fukuoka General Hospital
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Medical Center
city: Gifu
country: Japan
facility: Gifu Prefectural General Medical Center
city: Hiroshima
country: Japan
facility: Hiroshima City Hiroshima Citizens Hospital
city: Kochi
country: Japan
facility: Chikamori Hospital
city: Kumamoto
country: Japan
facility: Saiseikai Kumamoto Hospital
city: Kumamoto
country: Japan
facility: Japanese Red Cross Kumamoto Hospital
city: Kyoto
country: Japan
facility: Ijinkai Takeda General Hospital
city: Nagano
country: Japan
facility: Nagano Municipal Hospital
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum (AMC)
city: Heerlen
country: Netherlands
facility: Zuyderland Medisch Centrum
city: Nieuwegein
country: Netherlands
facility: St. Antonius Ziekenhuis
city: Zwolle
country: Netherlands
facility: Isala
city: Gdansk
country: Poland
facility: Copernicus PL, M.Kopernik Hospital
city: Grodzisk Mazowiecki
country: Poland
facility: Samodzielny Publiczny Specjalistyczny Szpital Zachodni
city: Katowice
country: Poland
facility: Gornoslaskie CM im. Prof. Leszka Gieca SUM w Katowicach
city: Krakow
country: Poland
facility: Szpital Uniwersytecki w Krakowie
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 4
city: Ostroleka
country: Poland
facility: Mazowiecki Szpital Specjalistyczny im. dr. Jozefa Psarskiego
city: Warszawa
country: Poland
facility: Wojskowy Instytut Medyczny
city: Loures
country: Portugal
facility: Luz Saude | Hospital Beatriz Angelo - Centro de Investigacao Clinica
state: Lisboa
city: Matosinhos
country: Portugal
facility: ULSM - Hospital Pedro Hispano
state: Porto
city: Almada
country: Portugal
facility: Hospital Garcia de Orta | Research Department
state: Setúbal
city: Coimbra
country: Portugal
facility: CHUC - Hospitais da U. Coimbra - Servico de Neurologia
city: Lisboa
country: Portugal
facility: CHLO - Hospital Egas Moniz
city: Lisboa
country: Portugal
facility: Hospital da Luz - Lisboa
city: Lisboa
country: Portugal
facility: CHULN - Hospital Santa Maria
city: Porto
country: Portugal
facility: CHUSJ - Hospital Sao Joao
city: Chelyabinsk
country: Russian Federation
facility: City Clinical Hospital #3
city: Kemerovo
country: Russian Federation
facility: Sci-Res. Institute of Complex Cardiovascular Disorders
city: Krasnodar
country: Russian Federation
facility: Regional Clinical Hospital #1 n.a. prof. S.V. Ochapovsky
city: Novosibirsk
country: Russian Federation
facility: Railway clinical hospital on the station Novosibirsk-Glavniy
city: Sestroretsk
country: Russian Federation
facility: City clinical hospital #40 Sestroretsk
city: Tomsk
country: Russian Federation
facility: Tomsk Regional Clinical Hospital
city: Vsevolozhsk
country: Russian Federation
facility: Clinical Inter-District Hospital of Vsevolozhsk
city: Yekaterinburg
country: Russian Federation
facility: Sverdlovsk Regional Clinical Hospital #1
city: Bratislava
country: Slovakia
facility: Univerzitna nemocnica Bratislava, Nemocnica Stare Mesto
city: Dolny Kubin
country: Slovakia
facility: Dolnooravska nemocnica s poliklinikou L. Nadasi Jegeho
city: Levoca
country: Slovakia
facility: Vseobecna nemocnica s poliklinikou Levoca, a.s.
city: Liptovsky Mikulas
country: Slovakia
facility: Liptovska nemocnica s poliklinikou MUDr. Ivana Stodolu
city: Rimavska Sobota
country: Slovakia
facility: Svet zdravia, a. s. Vseobecna nemocnica Rimavska Sobota
city: Skalica
country: Slovakia
facility: Fakultna nemocnica AGEL Skalica, a.s.
city: Spisska Nova Ves
country: Slovakia
facility: Svet zdravia, a.s. Nemocnica s poliklinikou Spisska Nova Ves
city: Trnava
country: Slovakia
facility: Fakultna nemocnica Trnava
city: Ziar nad Hronom
country: Slovakia
facility: Vseobecna nemocnica v Ziari nad Hronom
city: Santiago de Compostela
country: Spain
facility: Hospital Clínico Universitario de Santiago de Compostela
state: A Coruña
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
state: Barcelona
city: Terrassa
country: Spain
facility: Hospital de la Mútua de Terrassa
state: Barcelona
city: Móstoles
country: Spain
facility: Hospital Rey Juan Carlos
state: Madrid
city: Albacete
country: Spain
facility: Complejo Hospitalario Universitario de Albacete | Hospital General Universitario - Neurology Department, Stroke Unit
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Ciutat Sanitaria i Universitaria de la Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau | Neurology Department - Stroke, No-Cardioembolic-Tia
city: Lleida
country: Spain
facility: Hospital Universitario Arnau de Vilanova de Lleida
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal | Neurology Department - Stroke, No-Cardioembolic-Tia
city: Madrid
country: Spain
facility: Hospital Clinico Universitario San Carlos | Neurologia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Valencia
country: Spain
facility: La Fe University and Polytechnic Hospital | Neurology Service - Vascular Unit
city: Valladolid
country: Spain
facility: Hospital Universitario Clinico de Valladolid | Neurology Department
city: Lund
country: Sweden
facility: Skånes Universitetssjukhus
city: Stockholm
country: Sweden
facility: Danderyds sjukhus
city: Umeå
country: Sweden
facility: Norrlands Universitetssjukhus, Umeå
city: Basel
country: Switzerland
facility: Universitätsspital Basel
state: Basel-Stadt
city: Biel
country: Switzerland
facility: Spitalzentrum Biel
state: Bern
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
state: Sankt Gallen
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Bern
country: Switzerland
facility: Inselspital Universitätsspital Bern
city: Lugano
country: Switzerland
facility: Ospedale regionale di Lugano
city: Chester
country: United Kingdom
facility: Countess of Chester Hospital
state: Cheshire
city: Wirral
country: United Kingdom
facility: Arrowe Park Hospital
state: Merseyside
city: Newcastle Upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
state: Tyne And Wear
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital
city: Coventry
country: United Kingdom
facility: University Hospitals Coventry and Warwickshire NHS Trust
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary | Glasgow Clinical Research Facility
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital
city: London
country: United Kingdom
facility: St George's Hospital
city: London
country: United Kingdom
facility: Charing Cross Hospital
Study officials:
References:
citation: 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.