E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Myocardial Infarction |
Infarto miocardico acuto
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E.1.1.1 | Medical condition in easily understood language |
Acute heart attack that happens when a blood vessel in the heart suddenly becomes blocked |
Infarto miocardico acuto
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To evaluate whether the oral FXIa inhibitor BAY 2433334 compared to placebo leads to a lower incidence of cardiovascular (CV) death, MI, stroke and stent thrombosis in participants with an acute myocardial infarction and who are treated with dual antiplatelet therapy. • To evaluate whether the incidence of bleeding is similar for BAY 2433334 compared to placebo in participants with an acute myocardial infarction and who are treated with dual antiplatelet therapy |
Valutare se l’inibitore del FXIa orale BAY 2433334, rispetto a placebo, comporti una minore incidenza di morte cardiovascolare (CV), IM, ictus e trombosi dello stent nei partecipanti con infarto miocardico acuto trattati con la doppia terapia antiaggregante. Valutare se l’incidenza del sanguinamento sia simile tra BAY 2433334 e placebo nei partecipanti con infarto miocardico acuto trattati con la doppia terapia antiaggregante.
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Participants must be 45 years of age or older, at the time of signing the informed consent 2. Acute myocardial infarction (excluding MI associated with PCI or CABG revascularization procedures) with: a.clinical symptoms of acute myocardial infarction AND b.elevated biomarkers of myocardial necrosis (creatine kinase-muscle and brain isoenzyme [CK-MB] or cardiac troponins) AND c.at least one of the following risk factors need to be fulfilled: i. Age = 65 years ii.Prior MI (before the index AMI event) iii.Prior peripheral arterial disease iv.Diabetes Mellitus v.Prior coronary artery bypass grafting (CABG) AND d. 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) 3. Plan for dual antiplatelet therapy (ASA + P2Y12 inhibitor) after hospital discharge for the index AMI 4. Randomization during hospitalization for the index AMI event and latest within 5 days of hospital admission 5. 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. |
1. Participants must be 45 years of age or older, at the time of signing the informed consent 2. Acute myocardial infarction (excluding MI associated with PCI or CABG revascularization procedures) with: a.clinical symptoms of acute myocardial infarction AND b.elevated biomarkers of myocardial necrosis (creatine kinase-muscle and brain isoenzyme [CK-MB] or cardiac troponins) AND c.at least one of the following risk factors need to be fulfilled: i. Age = 65 years ii.Prior MI (before the index AMI event) iii.Prior peripheral arterial disease iv.Diabetes Mellitus v.Prior coronary artery bypass grafting (CABG) AND d. 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) 3. Plan for dual antiplatelet therapy (ASA + P2Y12 inhibitor) after hospital discharge for the index AMI 4. Randomization during hospitalization for the index AMI event and latest within 5 days of hospital admission 5. 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.
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E.4 | Principal exclusion criteria |
1. Hemodynamically significant ventricular arrhythmias or cardiogenic shock at time of randomization 2. Active bleeding; known bleeding disorder, history of major bleeding (intracranial, retroperitoneal, intraocular) or clinically significant gastrointestinal bleeding within last 6 months of randomization 3. Planned use or requirement of full dose and long term anticoagulation therapy during study conduct |
1. Hemodynamically significant ventricular arrhythmias or cardiogenic shock at time of randomization 2. Active bleeding; known bleeding disorder, history of major bleeding (intracranial, retroperitoneal, intraocular) or clinically significant gastrointestinal bleeding within last 6 months of randomization 3. Planned use or requirement of full dose and long term anticoagulation therapy during study conduct
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy Endpoint Time from randomization to first occurrence of any of the components of the composite outcome including CV death, MI, stroke and stent thrombosis Safety Endpoint: Time from randomization to first occurrence of Bleeding Academic Research Consortium (BARC) bleeding definition type 2, 3 and 5 |
Endpoint primario di efficacia • composito di morte CV, IM, ictus e trombosi dello stent Endpoint primario di sicurezza • sanguinamenti BARC* di tipo 2, 3 e 5
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline up to 12 months |
Da basale fino a 12 mesi |
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E.5.2 | Secondary end point(s) |
Efficacy Endpoints: 1. Time from randomization to death (all cause mortality) 2. Time from randomization to CV death 3. Time from randomization to first occurrence of MI 4. Time from randomization to first occurrence of stroke (ischemic and hemorrhagic) 5. Time from randomization to first occurrence of stent thrombosis Safety Endpoints: 1. Time from randomization to first occurrence of all bleeding 2. Time from randomization to first occurrence of BARC bleeding definition Type 3, 5 3. Time from randomization to first occurrence of BARC bleeding definition Type 1, 2, 3, 5 |
Endpoint secondari di efficacia • mortalità per qualsiasi causa • morte CV • IM • ictus • trombosi dello stent
Endpoint secondari di sicurezza • tutti i sanguinamenti • sanguinamenti BARC* tipo 3, 5 • sanguinamenti BARC* tipo 1, 2, 3, 5 *BARC= Bleeding Academic Research Consortium
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From baseline up to 12 months |
Da basale fino a 12 mesi |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Dose-finding |
Dose-finding |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 120 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Belgium |
Canada |
Czechia |
Germany |
Hungary |
Italy |
Japan |
Netherlands |
Poland |
Spain |
Eswatini |
Sweden |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 24 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 24 |