E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Myocardial Infarction |
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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 |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064939 |
E.1.2 | Term | Cardiovascular event prophylaxis |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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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 |
There are two primary objectives to this trial being explored in patients who have experienced an acute myocardial infarction and are treated with dual antiplatelet therapy:
- 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. |
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E.2.2 | Secondary objectives of the trial |
In addition to the primary objectives, two exploratory objectives will also be explored as part of this study:
- To explore additional pharmacokinetic and pharmacodynamic parameters,biomarkers and genetics. - To further investigate the study intervention and similar drugs (i.e. mode-of-action-related effects and / or safety) and to further investigate pathomechanisms deemed relevant to cardiovascular diseases and associated health problems. |
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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 infarction1 (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 as described in Section 10.1.3 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
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Objectives: 1) 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.
2) 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.
Primary Efficacy Endpoint: 1) The composite of CV death, MI, Stroke and stent thrombosis
Primary Safety Endpoint: 1) Bleeding Academic Research Consortium (BARC) classification type 2, 3 and 5. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline up to 12 months. |
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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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From baseline up to 12 months. |
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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 |
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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 | 4 |
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 | No |
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 |
Czech Republic |
Germany |
Hungary |
Italy |
Japan |
Netherlands |
Poland |
Spain |
Sweden |
Switzerland |
United Kingdom |
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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LVLS: The end of the study is defined as the date of the last visit of the last participant in the study. |
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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 | 5 |
E.8.9.1 | In the Member State concerned days | 12 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 12 |