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

Phase 2

Completed

Conditions: Acute Myocardial Infarction

Interventions: Drug: BAY2433334
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

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.

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 cause
Safety - 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): 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
Cardiology Partners Clinical Research Institute
🇺🇸
Palm Beach Gardens, Florida, United States
Columbus Regional Research Institute
🇺🇸
Columbus, Georgia, United States
Reid Health
🇺🇸
Richmond, Indiana, United States
Midwest Heart & Vascular Specialists
🇺🇸
Overland Park, Kansas, United States
Cardiovascular Associates Research, LLC
🇺🇸
Covington, Louisiana, United States
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Valley Clinical Trials, Inc. - Covina
🇺🇸Covina, California, United States