Study to Gather Information About the Proper Dosing and Safety of the Oral FXIa Inhibitor BAY 2433334 in Patients Following an Acute Heart Attack

Acute Myocardial Infarction Clinical Trial

— PACIFIC-AMI  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04304534
• Other study ID #: 20603
• Secondary ID: 2019-003244-79
• Status: Completed
• Phase: Phase 2
• Start date: June 17, 2020
• Est. completion date: February 21, 2022

Study information

• Verified date: April 2023
• 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1601
• Est. completion date: February 21, 2022
• Est. primary completion date: February 21, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Infarction
• Myocardial Infarction

Intervention

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

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

Locations

Country	Name	City	State
Austria	Krankenhaus St. Josef Braunau	Braunau	Oberösterreich
Austria	Medizinische Universität Graz	Graz	Steiermark
Austria	Klinikum Klagenfurt am Wörthersee	Klagenfurt	Kärnten
Austria	Kepler Universitätsklinikum Campus III	Linz	Oberösterreich
Austria	Universitätsklinikum St. Pölten	St. Pölten	Niederösterreich
Austria	Klinik Floridsdorf - Krankenhaus Nord	Wien
Austria	Klinik Ottakring - Wilhelminenspital	Wien
Austria	Universitätsklinikum AKH Wien	Wien
Austria	Landesklinikum Wiener Neustadt	Wiener Neustadt	Niederösterreich
Belgium	OL Vrouwziekenhuis - Campus Aalst	Aalst
Belgium	Imeldaziekenhuis - St-Elisabethkliniek	Bonheiden
Belgium	AZ Sint-Jan Brugge-Oostende | Sint-Jan - Cardiology	Brugge
Belgium	CU Saint-Luc/UZ St-Luc	Bruxelles - Brussel
Belgium	Ziekenhuis Oost-Limburg	Genk
Belgium	Jessa Ziekenhuis	Hasselt
Belgium	UZ Leuven Gasthuisberg	Leuven
Belgium	CHR de la Citadelle - Cardiology	Liege
Czechia	Fakultni nemocnice Brno	Brno
Czechia	Fakultni nemocnice u sv. Anny	Brno
Czechia	Nemocnice Ceske Budejovice, a.s. Department of kardiologie	Ceske Budejovice
Czechia	Fakultni Nemocnice Hradec Kralove	Hradec Kralove
Czechia	Fakultni nemocnice Plzen - Lochotin	Plzen
Czechia	Fakultni nemocnice Kralovske Vinohrady	Praha 10
Czechia	Vseobecna fakultni nemocnice v Praze	Praha 2
Czechia	Institut Klinicke a Experimentalni Mediciny	Praha 4
Czechia	Fakultni nemocnice v Motole	Praha 5
Czechia	Ustredni vojenska nemocnice Praha	Praha 6
Czechia	Nemocnice Slany	Slany
Germany	Universitätsherzzentrum Freiburg - Bad Krozingen	Bad Krozingen	Baden-Württemberg
Germany	Krankenhaus Dresden-Friedrichstadt	Dresden	Sachsen
Germany	Universitätsklinikum Essen	Essen	Nordrhein-Westfalen
Germany	Universitätsklinikum Hamburg Eppendorf (UKE)	Hamburg
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	St. Vinzenz-Hospital	Köln	Nordrhein-Westfalen
Germany	Universitätsmedizin der Johannes Gutenberg Universität Mainz	Mainz	Rheinland-Pfalz
Germany	Kliniken Maria Hilf GmbH	Mönchengladbach	Nordrhein-Westfalen
Germany	Sana-Klinikum Remscheid GmbH	Remscheid	Nordrhein-Westfalen
Germany	Forschungszentrum Ruhr - KliFoCenter GmbH	Witten	Nordrhein-Westfalen
Hungary	Allami Szivkorhaz	Balatonfured
Hungary	Budai Irgalmasrendi Korhaz	Budapest
Hungary	Eszak-Pesti Centrumkorhaz-Honvedkorhaz	Budapest
Hungary	University of Semmelweis/ Semmelweis Egyetem	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont	Debrecen
Hungary	Petz Aladar Megyei Oktato Korhaz	Gyor
Hungary	Pandy Kalman Korhaz	Gyula
Hungary	Somogy Megyei Kaposi Mor Oktato Korhaz	Kaposvar
Hungary	Josa Andras Hospital	Nyiregyhaza
Hungary	Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz	Szolnok
Hungary	Zala Megyei Szent Rafael Korhaz	Zalaegerszeg
Italy	A.O.U. Ospedali Riuniti "Umberto I - G.M.Lancisi - G.Salesi"	Ancona	Marche
Italy	A.O. San Pio	Benevento	Campania
Italy	ASL Caserta	Caserta	Campania
Italy	A.O. S.Croce e Carle	Cuneo	Piemonte
Italy	A.O.U. di Ferrara	Ferrara	Emilia-Romagna
Italy	IRCCS Ospedale Policlinico San Martino	Genova	Liguria
Italy	AUSL Toscana Sud-Est	Grosseto	Toscana
Italy	IRCCS Centro Cardiologico Monzino S.p.A	Milano	Lombardia
Italy	Istituto Clinico Humanitas - Humanitas Mirasole S.p.A.	Milano	Lombardia
Italy	Asl Roma 2	Roma	Lazio
Italy	A.O.U. di Sassari	Sassari	Sardegna
Italy	ASL TO3 di Collegno e Pinerolo	Torino	Piemonte
Italy	ASST Valle Olona	Varese	Lombardia
Italy	ULSS3 Serenissima	Venezia	Veneto
Japan	Tokyo Medical and Dental University Hospital	Bunkyo-ku	Tokyo
Japan	Fukui Prefectural Hospital	Fukui
Japan	Japanese Red Cross Fukuoka Hospital	Fukuoka
Japan	Hyogo Prefectural Harima-Himeji General Medical Center	Himeji	Hyogo
Japan	Fukuoka Tokushukai Hospital	Kasuga	Fukuoka
Japan	Kishiwada Tokushukai Hospital	Kishiwada	Osaka
Japan	Kokura Memorial Hospital	Kitakyushu	Fukuoka
Japan	Takahashi Hospital	Kobe	Hyogo
Japan	Shin-Kuki General Hospital	Kuki	Saitama
Japan	Saiseikai Kumamoto Hospital	Kumamoto
Japan	Chiba-Nishi General Hospital	Matsudo	Chiba
Japan	Daido Hospital, Social Medical Corporation Kojunkai	Nagoya	Aichi
Japan	Nishinomiya Watanabe Cardiovascular Center	Nishinomiya	Hyogo
Japan	Ogaki Municipal Hospital	Ogaki	Gifu
Japan	Oita Prefectural Hospital	Oita
Japan	Osaka General Medical Center	Osaka
Japan	Hokkaido Cardiovascular Hospital	Sapporo	Hokkaido
Japan	Saitama Sekishinkai Hospital	Sayama	Saitama
Japan	Tsukuba Medical Center Hospital	Tsukuba	Ibaraki
Japan	Kanagawa Cardiovascular and Respiratory Center	Yokohama	Kanagawa
Netherlands	Noord West Ziekenhuisgroep-Medisch Centrum Alkmaar	Alkmaar
Netherlands	Reinier de Graaf Gasthuis	Delft
Netherlands	Jeroen Bosch Ziekenhuis	Den Bosch
Netherlands	Albert Schweitzer Ziekenhuis, Dordwijk	Dordrecht
Netherlands	Zuyderland Medisch Centrum	Heerlen
Netherlands	Elkerliek Ziekenhuis, Lokatie Helmond	Helmond
Netherlands	Leids Universitair Medisch Centrum	Leiden
Netherlands	Canisius Wilhelmina Ziekenhuis	Nijmegen
Netherlands	Universitair Medisch Centrum St. Radboud	Nijmegen
Netherlands	Bravis Ziekenhuis	Roosendaal
Netherlands	Ikazia Ziekenhuis	Rotterdam
Netherlands	VieCuri - Medisch Centrum voor Noord-Limburg locatie Venlo	Venlo
Netherlands	Gelre Ziekenhuizen Zutphen	Zutphen
Netherlands	Isala	Zwolle
Poland	Uniwersytecki Szpital Kliniczny w Bialymstoku	Bialystok
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	Szpital Grochowski im. dr.med. Rafala Masztaka	Warszawa
Poland	Uniwersyteckie Centrum Kliniczne Warszawskiego UM	Warszawa
Poland	Uniwersytecki Szpital Kliniczny UM we Wroclawiu	Wroclaw
Spain	Ciutat Sanitaria i Universitaria de la Vall d'Hebron	Barcelona
Spain	Hospital de la Santa Creu i de Sant Pau | Cardiología	Barcelona
Spain	Hospital Universitari de Bellvitge | Bellvitge Biomedical Research Institute - Cardiology - AF, Stroke Prevention	Barcelona
Spain	Hospital Universitario Virgen de las Nieves|Cardiologia	Granada
Spain	Hospital Clinico Universitario San Carlos | Cardiologia	Madrid
Spain	Hospital Ramon y Cajal | Cardiologia	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Clinico Universitario Virgen de la Arrixaca | Neurology Department - Stroke	Murcia
Spain	Hospital Universitario Virgen de la Macarena	Sevilla
Spain	Inst Investigacio Sanitaria Pere Virgili | Hosp Univ Joan XXIII de Tarragona - Neurology - Stroke, No-Cardioembolic-Tia	Tarragona
Spain	Hospital Gral. Univ. de Valencia | Cardiologia	Valencia
Spain	Hospital Universitari i Politècnic La Fe | Cardiología	Valencia
Sweden	Falu Lasarett	Falun
Sweden	Sahlgrenska Universitetssjukhuset	Göteborg
Sweden	Länssjukhuset Ryhov	Jönköping
Sweden	Skånes Universitetssjukhus	Lund
Sweden	Universitetssjukhuset Örebro	Örebro
Sweden	Danderyds sjukhus	Stockholm
Sweden	Länssjukhuset Sundsvall-Härnösand	Sundsvall
Sweden	Akademiska sjukhuset Hjärtforskningsmottagningen	Uppsala
Sweden	Västmanlands Sjukhus Västerås	Västerås
Switzerland	Kantonsspital Aarau	Aarau	Aargau
Switzerland	Kantonsspital Baden	Baden
Switzerland	Hôpital Cantonal Universitaire de Genève	Genève
Switzerland	Centre Hospitalier Universitaire Vaudois (CHUV)	Lausanne	Vaud
Switzerland	Kantonsspital Baselland - Standort Liestal	Liestal	Basel-Landschaft
Switzerland	Ospedale regionale di Lugano	Lugano
Switzerland	Luzerner Kantonsspital	Luzern
United Kingdom	Imperial College London	London
United Kingdom	Wythenshawe Hospital	Manchester
United Kingdom	Freeman Hospital	Newcastle Upon Tyne	Tyne And Wear
United Kingdom	Lister Hospital	Stevenage	Hertfordshire
United Kingdom	Worcestershire Acute Hospital Trust	Worcester	Worcestershire
United States	PharmaTex Research, LLC	Amarillo	Texas
United States	Maryland Cardiovascular Specialists	Baltimore	Maryland
United States	Florida Premier Cardiology	Boynton Beach	Florida
United States	Trinity Medical WNY	Cheektowaga	New York
United States	Clearwater Cardiovascular Associates | Clearwater, FL	Clearwater	Florida
United States	Columbus Regional Research Institute	Columbus	Georgia
United States	Valley Clinical Trials, Inc. - Covina	Covina	California
United States	Cardiovascular Associates Research, LLC	Covington	Louisiana
United States	Cardiology Associates Research Company	Daytona Beach	Florida
United States	St. Mary's/Duluth Clinic Health System	Duluth	Minnesota
United States	Logan Health Research	Kalispell	Montana
United States	North Texas Research Associates	McKinney	Texas
United States	Southwest Florida Research	Naples	Florida
United States	Methodist Physicians Clinic	Omaha	Nebraska
United States	Midwest Heart & Vascular Specialists	Overland Park	Kansas
United States	Cardiology Partners Clinical Research Institute	Palm Beach Gardens	Florida
United States	Jefferson Heart Institute	Philadelphia	Pennsylvania
United States	Cardiovascular Research of Knoxville	Powell	Tennessee
United States	Reid Health	Richmond	Indiana
United States	The Valley Hospital, Inc.	Ridgewood	New Jersey
United States	White Oak Medical Center	Silver Spring	Maryland
United States	Southern Clinical Research, LLC	Zachary	Louisiana

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Czechia,  Germany,  Hungary,  Italy,  Japan,  Netherlands,  Poland,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy - Number of Participants With Composite of CV Death, MI, Stroke and Stent Thrombosis (ST)	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 cause	From baseline up to 52 weeks
Primary	Safety - Number of Participants With BARC Bleeding Definition Type 2, 3 and 5	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.	From baseline up to 52 weeks
Secondary	Efficacy - Number of Participants With CV Death	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.	From baseline up to 52 weeks
Secondary	Efficacy - Number of Participants With MI	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.	From baseline up to 52 weeks
Secondary	Efficacy - Number of Participants With Stroke	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.	From baseline up to 52 weeks
Secondary	Efficacy - Number of Participants With Stent Thrombosis	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	From baseline up to 52 weeks
Secondary	Efficacy - Number of Participants With All Cause Mortality		From baseline up to 52 weeks
Secondary	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
Secondary	Safety - Number of Participants With BARC Bleeding Definition Type 3, 5	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.	From baseline up to 52 weeks
Secondary	Safety - Number of Participants With BARC Bleeding Definition Type 1,2,3,5	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.	From baseline up to 52 weeks

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