Study to Gather Information About the Proper Dosing and Safety of the Oral FXIa Inhibitor BAY 2433334 in Patients Following an Acute Heart Attack
- Conditions
- Acute Myocardial Infarction
- Interventions
- Other: BAY2433334 matching placebo
- Registration Number
- NCT04304534
- Lead Sponsor
- Bayer
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1601
-
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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BAY 2433334 high dose BAY2433334 - BAY 2433334 medium dose BAY2433334 - BAY 2433334 low dose BAY2433334 - BAY2433334 matching placebo BAY2433334 matching placebo -
- Primary Outcome Measures
Name Time Method Efficacy - Number of Participants With Composite of CV Death, MI, Stroke and Stent Thrombosis (ST) From baseline up to 52 weeks 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.
Stroke was defined as an acute episode of focal or global neurological dysfunction caused by an injury of the brain, spinal cord, or retina as a result of hemorrhage or infarction.
ST was defined incorporating diagnostic certainty as well as timing: "Definite" ST: The highest level of certainty. Either angiographic or pathological confirmation of stent thrombosis. "Probable" ST: Regardless of the time after the index procedure, any MI that is related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis and in the absence of any other obvious causeSafety - Number of Participants With BARC Bleeding Definition Type 2, 3 and 5 From baseline up to 52 weeks Type 2: any overt, actionable sign of hemorrhage that doesn't fit the criteria for type 3 or 5 but meets at least one of the following criteria: 1) requires nonsurgical, med intervention by a HCP, 2) leads to hospital or rise in level of care, or 3) prompt eval. Type 3a: 1) overt bleed + Hg drop of 3 to \<5 g/dl (provided Hg drop is related to bleed); 2 any transfusion with overt bleed. Type 3b: 1) overt bleed + Hg drop ≥5 g/dL (provided Hg drop is related to bleed); 2) cardiac tamponade; 3) bleed requiring surgical intervention for control (exclude dental/nasal /skin/hemorrhoid); 4) bleed requiring IV vasoactive agents. Type 3c: 1) ICH hemorrhage (doesn't include microbleeds or HT, does include intraspinal); subcategories confirmed by autopsy or imaging or LP; 2) intraocular bleed compromising vision. Type 5: fatal bleed. Type 5a: probable fatal bleed; no autopsy or image confirmation but clinical suspicion. Type 5b: definite fatal bleed; overt bleed or autopsy or image confirmation.
- Secondary Outcome Measures
Name Time Method Efficacy - Number of Participants With CV Death From baseline up to 52 weeks 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.
Efficacy - Number of Participants With MI From baseline up to 52 weeks 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 requires combination of: 1. Presence of acute myocardial injury. 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.
Efficacy - Number of Participants With Stroke From baseline up to 52 weeks Stroke was defined as an acute episode of focal or global neurological dysfunction caused by an injury of the brain, spinal cord, or retina as a result of hemorrhage or infarction.
Efficacy - Number of Participants With Stent Thrombosis From baseline up to 52 weeks ST was defined incorporating diagnostic certainty as well as timing: "Definite" ST: The highest level of certainty. Either angiographic or pathological confirmation of stent thrombosis. "Probable" ST: Regardless of the time after the index procedure, any MI that is related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis and in the absence of any other obvious cause
Efficacy - Number of Participants With All Cause Mortality From baseline up to 52 weeks Safety - Number of Participants With All Bleeding From baseline up to 52 weeks All bleeding events occurred from first intake of study intervention until 2 days after the last intake of study intervention
Safety - Number of Participants With BARC Bleeding Definition Type 3, 5 From baseline up to 52 weeks Type 3a: 1) overt bleed + Hg drop of 3 to \<5 g/dl (provided Hg drop is related to bleed); 2 any transfusion with overt bleed. Type 3b: 1) overt bleed + Hg drop ≥5 g/dL (provided Hg drop is related to bleed); 2) cardiac tamponade; 3) bleed requiring surgical intervention for control (exclude dental/nasal /skin/hemorrhoid); 4) bleed requiring IV vasoactive agents. Type 3c: 1) ICH hemorrhage (doesn't include microbleeds or HT, does include intraspinal); subcategories confirmed by autopsy or imaging or LP; 2) intraocular bleed compromising vision. Type 5: fatal bleed. Type 5a: probable fatal bleed; no autopsy or image confirmation but clinical suspicion. Type 5b: definite fatal bleed; overt bleed or autopsy or image confirmation.
Safety - Number of Participants With BARC Bleeding Definition Type 1,2,3,5 From baseline up to 52 weeks Type 1: bleeding that is not actionable and does not cause the patient to seek unscheduled performance of studies, hospitalization, or treatment by a healthcare professional; may include episodes leading to self-discontinuation of medical therapy by the patient without consulting a healthcare professional. For BARC bleeding definition 2,3 and 5, please refer to second primary endpoint.
Trial Locations
- Locations (160)
Maryland Cardiovascular Specialists
🇺🇸Baltimore, Maryland, United States
Logan Health Research
🇺🇸Kalispell, Montana, United States
Reinier de Graaf Gasthuis
🇳🇱Delft, Netherlands
Zuyderland Medisch Centrum
🇳🇱Heerlen, Netherlands
VieCuri - Medisch Centrum voor Noord-Limburg locatie Venlo
🇳🇱Venlo, Netherlands
Landesklinikum Wiener Neustadt
🇦🇹Wiener Neustadt, Niederösterreich, Austria
Petz Aladar Megyei Oktato Korhaz
🇭🇺Gyor, Hungary
Uniwersytecki Szpital Kliniczny w Bialymstoku
🇵🇱Bialystok, Poland
Centre Hospitalier Universitaire Vaudois (CHUV)
🇨🇭Lausanne, Vaud, Switzerland
Universitätsherzzentrum Freiburg - Bad Krozingen
🇩🇪Bad Krozingen, Baden-Württemberg, Germany
Debreceni Egyetem Klinikai Kozpont
🇭🇺Debrecen, Hungary
Lister Hospital
🇬🇧Stevenage, Hertfordshire, United Kingdom
Worcestershire Acute Hospital Trust
🇬🇧Worcester, Worcestershire, United Kingdom
IRCCS Ospedale Policlinico San Martino
🇮🇹Genova, Liguria, Italy
Krankenhaus St. Josef Braunau
🇦🇹Braunau, Oberösterreich, Austria
Medizinische Universität Graz
🇦🇹Graz, Steiermark, Austria
Pandy Kalman Korhaz
🇭🇺Gyula, Hungary
Asl Roma 2
🇮🇹Roma, Lazio, Italy
Ospedale regionale di Lugano
🇨🇭Lugano, Switzerland
Hôpital Cantonal Universitaire de Genève
🇨🇭Genève, Switzerland
Uniwersyteckie Centrum Kliniczne Warszawskiego UM
🇵🇱Warszawa, Poland
Luzerner Kantonsspital
🇨🇭Luzern, Switzerland
ASST Valle Olona
🇮🇹Varese, Lombardia, Italy
A.O.U. di Sassari
🇮🇹Sassari, Sardegna, Italy
Danderyds sjukhus
🇸🇪Stockholm, Sweden
Midwest Heart & Vascular Specialists
🇺🇸Overland Park, Kansas, United States
Cardiology Partners Clinical Research Institute
🇺🇸Palm Beach Gardens, Florida, United States
Reid Health
🇺🇸Richmond, Indiana, United States
Trinity Medical WNY
🇺🇸Cheektowaga, New York, United States
The Valley Hospital, Inc.
🇺🇸Ridgewood, New Jersey, United States
St. Mary's/Duluth Clinic Health System
🇺🇸Duluth, Minnesota, United States
Cardiovascular Research of Knoxville
🇺🇸Powell, Tennessee, United States
White Oak Medical Center
🇺🇸Silver Spring, Maryland, United States
Klinikum Klagenfurt am Wörthersee
🇦🇹Klagenfurt, Kärnten, Austria
Kepler Universitätsklinikum Campus III
🇦🇹Linz, Oberösterreich, Austria
CHR de la Citadelle - Cardiology
🇧🇪Liege, Belgium
Krankenhaus Dresden-Friedrichstadt
🇩🇪Dresden, Sachsen, Germany
Fakultni nemocnice Brno
🇨🇿Brno, Czechia
Universitätsklinikum AKH Wien
🇦🇹Wien, Austria
Klinik Ottakring - Wilhelminenspital
🇦🇹Wien, Austria
Klinik Floridsdorf - Krankenhaus Nord
🇦🇹Wien, Austria
OL Vrouwziekenhuis - Campus Aalst
🇧🇪Aalst, Belgium
Imeldaziekenhuis - St-Elisabethkliniek
🇧🇪Bonheiden, Belgium
CU Saint-Luc/UZ St-Luc
🇧🇪Bruxelles - Brussel, Belgium
Ziekenhuis Oost-Limburg
🇧🇪Genk, Belgium
Jessa Ziekenhuis
🇧🇪Hasselt, Belgium
UZ Leuven Gasthuisberg
🇧🇪Leuven, Belgium
Fakultni nemocnice u sv. Anny
🇨🇿Brno, Czechia
Universitätsmedizin der Johannes Gutenberg Universität Mainz
🇩🇪Mainz, Rheinland-Pfalz, Germany
Nemocnice Slany
🇨🇿Slany, Czechia
Institut Klinicke a Experimentalni Mediciny
🇨🇿Praha 4, Czechia
Ustredni vojenska nemocnice Praha
🇨🇿Praha 6, Czechia
Allami Szivkorhaz
🇭🇺Balatonfured, Hungary
St. Vinzenz-Hospital
🇩🇪Köln, Nordrhein-Westfalen, Germany
Budai Irgalmasrendi Korhaz
🇭🇺Budapest, Hungary
Zala Megyei Szent Rafael Korhaz
🇭🇺Zalaegerszeg, Hungary
IRCCS Centro Cardiologico Monzino S.p.A
🇮🇹Milano, Lombardia, Italy
ASL TO3 di Collegno e Pinerolo
🇮🇹Torino, Piemonte, Italy
A.O.U. Ospedali Riuniti "Umberto I - G.M.Lancisi - G.Salesi"
🇮🇹Ancona, Marche, Italy
Eszak-Pesti Centrumkorhaz-Honvedkorhaz
🇭🇺Budapest, Hungary
Josa Andras Hospital
🇭🇺Nyiregyhaza, Hungary
Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz
🇭🇺Szolnok, Hungary
Daido Hospital, Social Medical Corporation Kojunkai
🇯🇵Nagoya, Aichi, Japan
Takahashi Hospital
🇯🇵Kobe, Hyogo, Japan
Fukuoka Tokushukai Hospital
🇯🇵Kasuga, Fukuoka, Japan
Tokyo Medical and Dental University Hospital
🇯🇵Bunkyo-ku, Tokyo, Japan
Leids Universitair Medisch Centrum
🇳🇱Leiden, Netherlands
Universitair Medisch Centrum St. Radboud
🇳🇱Nijmegen, Netherlands
Shin-Kuki General Hospital
🇯🇵Kuki, Saitama, Japan
Fukui Prefectural Hospital
🇯🇵Fukui, Japan
Kishiwada Tokushukai Hospital
🇯🇵Kishiwada, Osaka, Japan
Saitama Sekishinkai Hospital
🇯🇵Sayama, Saitama, Japan
Hospital de la Santa Creu i de Sant Pau | Cardiología
🇪🇸Barcelona, Spain
Elkerliek Ziekenhuis, Lokatie Helmond
🇳🇱Helmond, Netherlands
Ikazia Ziekenhuis
🇳🇱Rotterdam, Netherlands
Szpital Grochowski im. dr.med. Rafala Masztaka
🇵🇱Warszawa, Poland
Szpital sw. Wincentego a Paulo
🇵🇱Gdynia, Poland
Samodzielny Publiczny Specjalistyczny Szpital Zachodni
🇵🇱Grodzisk Mazowiecki, Poland
Uniwersytecki Szpital Kliniczny w Opolu
🇵🇱Opole, Poland
Kliniczny Szpital Wojewodzki Nr 2 im. Sw. Jadwigi Krolowej
🇵🇱Rzeszow, Poland
Uniwersytecki Szpital Kliniczny UM we Wroclawiu
🇵🇱Wroclaw, Poland
Kantonsspital Baden
🇨🇭Baden, Switzerland
Hospital Clinico Universitario Virgen de la Arrixaca | Neurology Department - Stroke
🇪🇸Murcia, Spain
Hospital Gral. Univ. de Valencia | Cardiologia
🇪🇸Valencia, Spain
Kantonsspital Aarau
🇨🇭Aarau, Aargau, Switzerland
Falu Lasarett
🇸🇪Falun, Sweden
Inst Investigacio Sanitaria Pere Virgili | Hosp Univ Joan XXIII de Tarragona - Neurology - Stroke, No-Cardioembolic-Tia
🇪🇸Tarragona, Spain
Länssjukhuset Ryhov
🇸🇪Jönköping, Sweden
Skånes Universitetssjukhus
🇸🇪Lund, Sweden
Hospital Clinico Universitario San Carlos | Cardiologia
🇪🇸Madrid, Spain
Hospital Universitario Virgen de las Nieves|Cardiologia
🇪🇸Granada, Spain
Ogaki Municipal Hospital
🇯🇵Ogaki, Gifu, Japan
Hyogo Prefectural Harima-Himeji General Medical Center
🇯🇵Himeji, Hyogo, Japan
Hokkaido Cardiovascular Hospital
🇯🇵Sapporo, Hokkaido, Japan
Japanese Red Cross Fukuoka Hospital
🇯🇵Fukuoka, Japan
Saiseikai Kumamoto Hospital
🇯🇵Kumamoto, Japan
Sana-Klinikum Remscheid GmbH
🇩🇪Remscheid, Nordrhein-Westfalen, Germany
Forschungszentrum Ruhr - KliFoCenter GmbH
🇩🇪Witten, Nordrhein-Westfalen, Germany
Methodist Physicians Clinic
🇺🇸Omaha, Nebraska, United States
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitari i Politècnic La Fe | Cardiología
🇪🇸Valencia, Spain
Nemocnice Ceske Budejovice, a.s. Department of kardiologie
🇨🇿Ceske Budejovice, Czechia
Fakultni Nemocnice Hradec Kralove
🇨🇿Hradec Kralove, Czechia
Fakultni nemocnice v Motole
🇨🇿Praha 5, Czechia
Valley Clinical Trials, Inc. - Covina
🇺🇸Covina, California, United States
Florida Premier Cardiology
🇺🇸Boynton Beach, Florida, United States
Clearwater Cardiovascular Associates | Clearwater, FL
🇺🇸Clearwater, Florida, United States
Cardiology Associates Research Company
🇺🇸Daytona Beach, Florida, United States
Southwest Florida Research
🇺🇸Naples, Florida, United States
Cardiovascular Associates Research, LLC
🇺🇸Covington, Louisiana, United States
Southern Clinical Research, LLC
🇺🇸Zachary, Louisiana, United States
Jefferson Heart Institute
🇺🇸Philadelphia, Pennsylvania, United States
PharmaTex Research, LLC
🇺🇸Amarillo, Texas, United States
North Texas Research Associates
🇺🇸McKinney, Texas, United States
Universitätsklinikum St. Pölten
🇦🇹St. Pölten, Niederösterreich, Austria
AZ Sint-Jan Brugge-Oostende | Sint-Jan - Cardiology
🇧🇪Brugge, Belgium
Fakultni nemocnice Plzen - Lochotin
🇨🇿Plzen, Czechia
Vseobecna fakultni nemocnice v Praze
🇨🇿Praha 2, Czechia
Fakultni nemocnice Kralovske Vinohrady
🇨🇿Praha 10, Czechia
Kliniken Maria Hilf GmbH
🇩🇪Mönchengladbach, Nordrhein-Westfalen, Germany
Universitätsklinikum Essen
🇩🇪Essen, Nordrhein-Westfalen, Germany
Universitätsklinikum Hamburg Eppendorf (UKE)
🇩🇪Hamburg, Germany
Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Germany
University of Semmelweis/ Semmelweis Egyetem
🇭🇺Budapest, Hungary
Somogy Megyei Kaposi Mor Oktato Korhaz
🇭🇺Kaposvar, Hungary
A.O. San Pio
🇮🇹Benevento, Campania, Italy
ASL Caserta
🇮🇹Caserta, Campania, Italy
A.O.U. di Ferrara
🇮🇹Ferrara, Emilia-Romagna, Italy
Istituto Clinico Humanitas - Humanitas Mirasole S.p.A.
🇮🇹Milano, Lombardia, Italy
AUSL Toscana Sud-Est
🇮🇹Grosseto, Toscana, Italy
A.O. S.Croce e Carle
🇮🇹Cuneo, Piemonte, Italy
ULSS3 Serenissima
🇮🇹Venezia, Veneto, Italy
Kokura Memorial Hospital
🇯🇵Kitakyushu, Fukuoka, Japan
Chiba-Nishi General Hospital
🇯🇵Matsudo, Chiba, Japan
Nishinomiya Watanabe Cardiovascular Center
🇯🇵Nishinomiya, Hyogo, Japan
Kanagawa Cardiovascular and Respiratory Center
🇯🇵Yokohama, Kanagawa, Japan
Tsukuba Medical Center Hospital
🇯🇵Tsukuba, Ibaraki, Japan
Akademiska sjukhuset Hjärtforskningsmottagningen
🇸🇪Uppsala, Sweden
Oita Prefectural Hospital
🇯🇵Oita, Japan
Osaka General Medical Center
🇯🇵Osaka, Japan
Noord West Ziekenhuisgroep-Medisch Centrum Alkmaar
🇳🇱Alkmaar, Netherlands
Jeroen Bosch Ziekenhuis
🇳🇱Den Bosch, Netherlands
Albert Schweitzer Ziekenhuis, Dordwijk
🇳🇱Dordrecht, Netherlands
Canisius Wilhelmina Ziekenhuis
🇳🇱Nijmegen, Netherlands
Bravis Ziekenhuis
🇳🇱Roosendaal, Netherlands
Gelre Ziekenhuizen Zutphen
🇳🇱Zutphen, Netherlands
Isala
🇳🇱Zwolle, Netherlands
Hospital Universitari de Bellvitge | Bellvitge Biomedical Research Institute - Cardiology - AF, Stroke Prevention
🇪🇸Barcelona, Spain
Ciutat Sanitaria i Universitaria de la Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Ramon y Cajal | Cardiologia
🇪🇸Madrid, Spain
Hospital Universitario Virgen de la Macarena
🇪🇸Sevilla, Spain
Sahlgrenska Universitetssjukhuset
🇸🇪Göteborg, Sweden
Länssjukhuset Sundsvall-Härnösand
🇸🇪Sundsvall, Sweden
Västmanlands Sjukhus Västerås
🇸🇪Västerås, Sweden
Kantonsspital Baselland - Standort Liestal
🇨🇭Liestal, Basel-Landschaft, Switzerland
Freeman Hospital
🇬🇧Newcastle Upon Tyne, Tyne And Wear, United Kingdom
Wythenshawe Hospital
🇬🇧Manchester, United Kingdom
Imperial College London
🇬🇧London, United Kingdom
Columbus Regional Research Institute
🇺🇸Columbus, Georgia, United States
Universitetssjukhuset Örebro
🇸🇪Örebro, Sweden