Clinical trial NCT04304534: Study to Gather Information About the Proper Dosing and Safety of the Oral FXIa Inhibitor BAY 2433334 in Patients Following an Acute Heart Attack
Official title: Multicenter, Randomized, Placebo Controlled, Double-blind, Parallel Group, Dose-finding Phase 2 Study to Evaluate the Efficacy and Safety of BAY 2433334 in Patients Following an Acute Myocardial Infarction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myocardial Infarction
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2020-03-11
Enrollment: 1601
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 a dual antiplatelet therapy (acetylsalicylic acid +/- clopidogrel) in patients following a recent heart attack (myocardial infarction) that happens when a blood vessel in the heart suddenly becomes blocked. 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:

* Participants must be 45 years of age or older, at the time of signing the informed consent
* Acute myocardial infarction (excluding MI associated with PCI or CABG revascularization procedures) with:

  * clinical symptoms of acute myocardial infarction AND
  * elevated biomarkers of myocardial necrosis (creatine kinase-muscle and brain isoenzyme \[CK-MB\] or cardiac troponins) AND
  * at least one of the following risk factors need to be fulfilled:

    * Age ≥ 65 years
    * Prior MI (before the index AMI event)
    * Prior peripheral arterial disease
    * Diabetes Mellitus
    * Prior coronary artery bypass grafting (CABG) AND
  * initial angiography and revascularization procedures, either PCI or CABG, as treatment for the index event performed before randomization. (Note: a planned, staged PCI procedure can be performed after randomization)
* Plan for dual antiplatelet therapy (ASA + P2Y12 inhibitor) after hospital discharge for the index AMI
* Randomization during hospitalization for the index AMI event and latest within 5 days of hospital admission
* Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent has to be signed before any study-specific procedure.

Exclusion Criteria:

* Hemodynamically significant ventricular arrhythmias or cardiogenic shock at time of randomization
* Active bleeding; known bleeding disorder, history of major bleeding (intracranial, retroperitoneal, intraocular) or clinically significant gastrointestinal bleeding within last 6 months of randomization
* Planned use or requirement of full dose and long term anticoagulation therapy during study conduct.

Primary outcomes:
measure: Efficacy - Number of Participants With Composite of CV Death, MI, Stroke and Stent Thrombosis (ST)
timeFrame: From baseline up to 52 weeks
measure: Safety - Number of Participants With BARC Bleeding Definition Type 2, 3 and 5
timeFrame: From baseline up to 52 weeks
Secondary outcomes:
measure: Efficacy - Number of Participants With CV Death
timeFrame: From baseline up to 52 weeks
measure: Efficacy - Number of Participants With MI
timeFrame: From baseline up to 52 weeks
measure: Efficacy - Number of Participants With Stroke
timeFrame: From baseline up to 52 weeks
measure: Efficacy - Number of Participants With Stent Thrombosis
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 BARC Bleeding Definition Type 3, 5
timeFrame: From baseline up to 52 weeks
measure: Safety - Number of Participants With BARC Bleeding Definition Type 1,2,3,5
timeFrame: From baseline up to 52 weeks
Other outcomes:
Locations:
city: Covina
country: United States
facility: Valley Clinical Trials, Inc. - Covina
state: California
city: Boynton Beach
country: United States
facility: Florida Premier Cardiology
state: Florida
city: Clearwater
country: United States
facility: Clearwater Cardiovascular Associates | Clearwater, FL
state: Florida
city: Daytona Beach
country: United States
facility: Cardiology Associates Research Company
state: Florida
city: Naples
country: United States
facility: Southwest Florida Research
state: Florida
city: Palm Beach Gardens
country: United States
facility: Cardiology Partners Clinical Research Institute
state: Florida
city: Columbus
country: United States
facility: Columbus Regional Research Institute
state: Georgia
city: Richmond
country: United States
facility: Reid Health
state: Indiana
city: Overland Park
country: United States
facility: Midwest Heart & Vascular Specialists
state: Kansas
city: Covington
country: United States
facility: Cardiovascular Associates Research, LLC
state: Louisiana
city: Zachary
country: United States
facility: Southern Clinical Research, LLC
state: Louisiana
city: Baltimore
country: United States
facility: Maryland Cardiovascular Specialists
state: Maryland
city: Silver Spring
country: United States
facility: White Oak Medical Center
state: Maryland
city: Duluth
country: United States
facility: St. Mary's/Duluth Clinic Health System
state: Minnesota
city: Kalispell
country: United States
facility: Logan Health Research
state: Montana
city: Omaha
country: United States
facility: Methodist Physicians Clinic
state: Nebraska
city: Ridgewood
country: United States
facility: The Valley Hospital, Inc.
state: New Jersey
city: Cheektowaga
country: United States
facility: Trinity Medical WNY
state: New York
city: Philadelphia
country: United States
facility: Jefferson Heart Institute
state: Pennsylvania
city: Powell
country: United States
facility: Cardiovascular Research of Knoxville
state: Tennessee
city: Amarillo
country: United States
facility: PharmaTex Research, LLC
state: Texas
city: McKinney
country: United States
facility: North Texas Research Associates
state: Texas
city: Klagenfurt
country: Austria
facility: Klinikum Klagenfurt am Wörthersee
state: Kärnten
city: St. Pölten
country: Austria
facility: Universitätsklinikum St. Pölten
state: Niederösterreich
city: Wiener Neustadt
country: Austria
facility: Landesklinikum Wiener Neustadt
state: Niederösterreich
city: Braunau
country: Austria
facility: Krankenhaus St. Josef Braunau
state: Oberösterreich
city: Linz
country: Austria
facility: Kepler Universitätsklinikum Campus III
state: Oberösterreich
city: Graz
country: Austria
facility: Medizinische Universität Graz
state: Steiermark
city: Wien
country: Austria
facility: Universitätsklinikum AKH Wien
city: Wien
country: Austria
facility: Klinik Ottakring - Wilhelminenspital
city: Wien
country: Austria
facility: Klinik Floridsdorf - Krankenhaus Nord
city: Aalst
country: Belgium
facility: OL Vrouwziekenhuis - Campus Aalst
city: Bonheiden
country: Belgium
facility: Imeldaziekenhuis - St-Elisabethkliniek
city: Brugge
country: Belgium
facility: AZ Sint-Jan Brugge-Oostende | Sint-Jan - Cardiology
city: Bruxelles - Brussel
country: Belgium
facility: CU Saint-Luc/UZ St-Luc
city: Genk
country: Belgium
facility: Ziekenhuis Oost-Limburg
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Liege
country: Belgium
facility: CHR de la Citadelle - Cardiology
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
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: Plzen
country: Czechia
facility: Fakultni nemocnice Plzen - Lochotin
city: Praha 10
country: Czechia
facility: Fakultni nemocnice Kralovske Vinohrady
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Praha 4
country: Czechia
facility: Institut Klinicke a Experimentalni Mediciny
city: Praha 5
country: Czechia
facility: Fakultni nemocnice v Motole
city: Praha 6
country: Czechia
facility: Ustredni vojenska nemocnice Praha
city: Slany
country: Czechia
facility: Nemocnice Slany
city: Bad Krozingen
country: Germany
facility: Universitätsherzzentrum Freiburg - Bad Krozingen
state: Baden-Württemberg
city: Essen
country: Germany
facility: Universitätsklinikum Essen
state: Nordrhein-Westfalen
city: Köln
country: Germany
facility: St. Vinzenz-Hospital
state: Nordrhein-Westfalen
city: Mönchengladbach
country: Germany
facility: Kliniken Maria Hilf GmbH
state: Nordrhein-Westfalen
city: Remscheid
country: Germany
facility: Sana-Klinikum Remscheid GmbH
state: Nordrhein-Westfalen
city: Witten
country: Germany
facility: Forschungszentrum Ruhr - KliFoCenter GmbH
state: Nordrhein-Westfalen
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg Universität Mainz
state: Rheinland-Pfalz
city: Dresden
country: Germany
facility: Krankenhaus Dresden-Friedrichstadt
state: Sachsen
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg Eppendorf (UKE)
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Balatonfured
country: Hungary
facility: Allami Szivkorhaz
city: Budapest
country: Hungary
facility: Budai Irgalmasrendi Korhaz
city: Budapest
country: Hungary
facility: University of Semmelweis/ Semmelweis Egyetem
city: Budapest
country: Hungary
facility: Eszak-Pesti Centrumkorhaz-Honvedkorhaz
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Gyor
country: Hungary
facility: Petz Aladar Megyei Oktato Korhaz
city: Gyula
country: Hungary
facility: Pandy Kalman Korhaz
city: Kaposvar
country: Hungary
facility: Somogy Megyei Kaposi Mor Oktato Korhaz
city: Nyiregyhaza
country: Hungary
facility: Josa Andras Hospital
city: Szolnok
country: Hungary
facility: Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz
city: Zalaegerszeg
country: Hungary
facility: Zala Megyei Szent Rafael Korhaz
city: Benevento
country: Italy
facility: A.O. San Pio
state: Campania
city: Caserta
country: Italy
facility: ASL Caserta
state: Campania
city: Ferrara
country: Italy
facility: A.O.U. di Ferrara
state: Emilia-Romagna
city: Roma
country: Italy
facility: Asl Roma 2
state: Lazio
city: Genova
country: Italy
facility: IRCCS Ospedale Policlinico San Martino
state: Liguria
city: Milano
country: Italy
facility: Istituto Clinico Humanitas - Humanitas Mirasole S.p.A.
state: Lombardia
city: Milano
country: Italy
facility: IRCCS Centro Cardiologico Monzino S.p.A
state: Lombardia
city: Varese
country: Italy
facility: ASST Valle Olona
state: Lombardia
city: Ancona
country: Italy
facility: A.O.U. Ospedali Riuniti "Umberto I - G.M.Lancisi - G.Salesi"
state: Marche
city: Cuneo
country: Italy
facility: A.O. S.Croce e Carle
state: Piemonte
city: Torino
country: Italy
facility: ASL TO3 di Collegno e Pinerolo
state: Piemonte
city: Sassari
country: Italy
facility: A.O.U. di Sassari
state: Sardegna
city: Grosseto
country: Italy
facility: AUSL Toscana Sud-Est
state: Toscana
city: Venezia
country: Italy
facility: ULSS3 Serenissima
state: Veneto
city: Nagoya
country: Japan
facility: Daido Hospital, Social Medical Corporation Kojunkai
state: Aichi
city: Matsudo
country: Japan
facility: Chiba-Nishi General Hospital
state: Chiba
city: Kasuga
country: Japan
facility: Fukuoka Tokushukai Hospital
state: Fukuoka
city: Kitakyushu
country: Japan
facility: Kokura Memorial Hospital
state: Fukuoka
city: Ogaki
country: Japan
facility: Ogaki Municipal Hospital
state: Gifu
city: Sapporo
country: Japan
facility: Hokkaido Cardiovascular Hospital
state: Hokkaido
city: Himeji
country: Japan
facility: Hyogo Prefectural Harima-Himeji General Medical Center
state: Hyogo
city: Kobe
country: Japan
facility: Takahashi Hospital
state: Hyogo
city: Nishinomiya
country: Japan
facility: Nishinomiya Watanabe Cardiovascular Center
state: Hyogo
city: Tsukuba
country: Japan
facility: Tsukuba Medical Center Hospital
state: Ibaraki
city: Yokohama
country: Japan
facility: Kanagawa Cardiovascular and Respiratory Center
state: Kanagawa
city: Kishiwada
country: Japan
facility: Kishiwada Tokushukai Hospital
state: Osaka
city: Kuki
country: Japan
facility: Shin-Kuki General Hospital
state: Saitama
city: Sayama
country: Japan
facility: Saitama Sekishinkai Hospital
state: Saitama
city: Bunkyo-ku
country: Japan
facility: Tokyo Medical and Dental University Hospital
state: Tokyo
city: Fukui
country: Japan
facility: Fukui Prefectural Hospital
city: Fukuoka
country: Japan
facility: Japanese Red Cross Fukuoka Hospital
city: Kumamoto
country: Japan
facility: Saiseikai Kumamoto Hospital
city: Oita
country: Japan
facility: Oita Prefectural Hospital
city: Osaka
country: Japan
facility: Osaka General Medical Center
city: Alkmaar
country: Netherlands
facility: Noord West Ziekenhuisgroep-Medisch Centrum Alkmaar
city: Delft
country: Netherlands
facility: Reinier de Graaf Gasthuis
city: Den Bosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis, Dordwijk
city: Heerlen
country: Netherlands
facility: Zuyderland Medisch Centrum
city: Helmond
country: Netherlands
facility: Elkerliek Ziekenhuis, Lokatie Helmond
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
city: Nijmegen
country: Netherlands
facility: Universitair Medisch Centrum St. Radboud
city: Nijmegen
country: Netherlands
facility: Canisius Wilhelmina Ziekenhuis
city: Roosendaal
country: Netherlands
facility: Bravis Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Ikazia Ziekenhuis
city: Venlo
country: Netherlands
facility: VieCuri - Medisch Centrum voor Noord-Limburg locatie Venlo
city: Zutphen
country: Netherlands
facility: Gelre Ziekenhuizen Zutphen
city: Zwolle
country: Netherlands
facility: Isala
city: Bialystok
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Bialymstoku
city: Gdynia
country: Poland
facility: Szpital sw. Wincentego a Paulo
city: Grodzisk Mazowiecki
country: Poland
facility: Samodzielny Publiczny Specjalistyczny Szpital Zachodni
city: Opole
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Opolu
city: Rzeszow
country: Poland
facility: Kliniczny Szpital Wojewodzki Nr 2 im. Sw. Jadwigi Krolowej
city: Warszawa
country: Poland
facility: Uniwersyteckie Centrum Kliniczne Warszawskiego UM
city: Warszawa
country: Poland
facility: Szpital Grochowski im. dr.med. Rafala Masztaka
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny UM we Wroclawiu
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 de Sant Pau | Cardiología
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge | Bellvitge Biomedical Research Institute - Cardiology - AF, Stroke Prevention
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves|Cardiologia
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal | Cardiologia
city: Madrid
country: Spain
facility: Hospital Clinico Universitario San Carlos | Cardiologia
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Murcia
country: Spain
facility: Hospital Clinico Universitario Virgen de la Arrixaca | Neurology Department - Stroke
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen de la Macarena
city: Tarragona
country: Spain
facility: Inst Investigacio Sanitaria Pere Virgili | Hosp Univ Joan XXIII de Tarragona - Neurology - Stroke, No-Cardioembolic-Tia
city: Valencia
country: Spain
facility: Hospital Gral. Univ. de Valencia | Cardiologia
city: Valencia
country: Spain
facility: Hospital Universitari i Politècnic La Fe | Cardiología
city: Falun
country: Sweden
facility: Falu Lasarett
city: Göteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset
city: Jönköping
country: Sweden
facility: Länssjukhuset Ryhov
city: Lund
country: Sweden
facility: Skånes Universitetssjukhus
city: Stockholm
country: Sweden
facility: Danderyds sjukhus
city: Sundsvall
country: Sweden
facility: Länssjukhuset Sundsvall-Härnösand
city: Uppsala
country: Sweden
facility: Akademiska sjukhuset Hjärtforskningsmottagningen
city: Västerås
country: Sweden
facility: Västmanlands Sjukhus Västerås
city: Örebro
country: Sweden
facility: Universitetssjukhuset Örebro
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau
state: Aargau
city: Liestal
country: Switzerland
facility: Kantonsspital Baselland - Standort Liestal
state: Basel-Landschaft
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois (CHUV)
state: Vaud
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Genève
country: Switzerland
facility: Hôpital Cantonal Universitaire de Genève
city: Lugano
country: Switzerland
facility: Ospedale regionale di Lugano
city: Luzern
country: Switzerland
facility: Luzerner Kantonsspital
city: Stevenage
country: United Kingdom
facility: Lister Hospital
state: Hertfordshire
city: Newcastle Upon Tyne
country: United Kingdom
facility: Freeman Hospital
state: Tyne And Wear
city: Worcester
country: United Kingdom
facility: Worcestershire Acute Hospital Trust
state: Worcestershire
city: London
country: United Kingdom
facility: Imperial College London
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital
Study officials:
References:
citation: Rao SV, Kirsch B, Bhatt DL, Budaj A, Coppolecchia R, Eikelboom J, James SK, Jones WS, Merkely B, Keller L, Hermanides RS, Campo G, Ferreiro JL, Shibasaki T, Mundl H, Alexander JH; PACIFIC AMI Investigators. A Multicenter, Phase 2, Randomized, Placebo-Controlled, Double-Blind, Parallel-Group, Dose-Finding Trial of the Oral Factor XIa Inhibitor Asundexian to Prevent Adverse Cardiovascular Outcomes After Acute Myocardial Infarction. Circulation. 2022 Oct 18;146(16):1196-1206. doi: 10.1161/CIRCULATIONAHA.122.061612. Epub 2022 Aug 27.