A Study to Learn How Well the Study Treatment Asundexian Works and How Safe it is Compared to Apixaban to Prevent Stroke or Systemic Embolism in People With Irregular and Often Rapid Heartbeat (Atrial Fibrillation), and at Risk for Stroke
- Summary
- Researchers are looking for a better way to treat people with atrial fibrillation (AF) and prevent stroke or systemic embolism (blood clots travelling through the blood stream to plug another vessel). Atrial fibrillation is a condition of having irregular and often rapid heartbeat. It can lead to the formation of blood clots in the heart which can travel through the blood stream to plug another vessel, and like this lead to serious and life-threatening conditions, such as a stroke. A stroke occurs because the brain tissue beyond the blockage no longer receives nutrients and oxygen so that brain cells die. As strokes arising from atrial fibrillation can involve extensive areas of the brain, it is important to prevent them. Blood clots are formed in a process known as coagulation. Medications are already available to prevent the formation of blood clots. When taken by mouth (orally), they are known as oral anticoagulants (OACs) including apixaban. OACs decrease the risk of the above-mentioned serious and life-threatening conditions. The main side effect of OACs is an increase of the risk of bleeding. The study treatment asundexian is a new type of anticoagulant currently under development to provide further treatment options. Asundexian aims to further improve the standard of care with regard to the risk of bleeding. The main purpose of this study is to collect more data about how well asundexian works to prevent stroke and systemic embolism and how safe it is compared to apixaban in people with atrial fibrillation and at high risk for stroke. To see how well the study treatment asundexian works researchers compare: * how long asundexian works well and * how long apixaban works well after the start of the treatment. Working well means that the treatments can prevent the following from happening: * stroke and/or * systemic embolism. The study will keep collecting data until a certain number of strokes or embolisms happen in the study. To see how safe asundexian is, the researchers will compare how often major bleedings occur after taking the study treatments asundexian and apixaban, respectively. Major bleedings are bleedings that have a serious or even life-threatening impact on a person's health. The study participants will be randomly (by chance) assigned to 1 of 2 treatment groups, A and B. Dependent on the treatment group, the participants will either take the study treatment asundexian by mouth once a day or apixaban by mouth twice a day for approximately 9 - 33 months. Each participant will be in the study for approximately 9 - 34 months. There will be visits to the study site every 3 to 6 months and up to 7 phone calls. Those participants who do not want or are unable to have visits to the study site may join the study remotely in selected locations. The location name contains the abbreviation - DCT in such cases. During the study, the study team will: * take blood samples * do physical examinations * examine heart health using an electrocardiogram (ECG) * check vital signs such as blood pressure and heart rate * do pregnancy tests * ask the participants questions about their quality of life * ask the participants questions about how they are feeling and what adverse events they are having. An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events that happen in studies, even if they do not think the adverse events might be related to the study treatments.
- Acronym
- OCEANIC-AF
- Short title
- A Study to Learn How Well the Study Treatment Asundexian Works and How Safe it is Compared to Apixaban to Prevent Stroke or Systemic Embolism in People With Irregular and Often Rapid Heartbeat (Atrial Fibrillation), and at Risk for Stroke
- Official title
- A Multicenter, International, Randomized, Active Comparator-controlled, Double-blind, Double-dummy, Parallel-group, 2-arm, Phase 3 Study to Compare the Efficacy and Safety of the Oral FXIa Inhibitor Asundexian (BAY 2433334) With Apixaban for the Prevention of Stroke or Systemic Embolism in Male and Female Participants Aged 18 Years and Older With Atrial Fibrillation at Risk for Stroke
- Control arm
- Active comparator
- Registry reports results
- Listing at source
- Listed
- Recruitment status
- Terminated
- Phase
- Phase 3
- Study type
- Interventional
- Reason stopped
- Independent Data Monitoring Committee (IDMC) recommendation to stop the study
- Completion date
- 2024-01-31
- First posted
- 2022-12-08
- Registry last updated
- 2024-12-09
- Primary completion date
- 2024-01-31
- Start date
- 2022-12-05
- Actual participants
- 14,830
- Participants
- 14,830
- Participant count basis
- Actual
- Protocol amendments
- Number of sites
- 1,069
- Data monitoring committee
- Registry sponsor category
- Industry
- Lead sponsor
- Bayer
- Source registry
- ClinicalTrials.gov
- Registry ID
- NCT05643573
- ClinicalTrials.gov ID
- NCT05643573
- Registry record
- Open registry record
- Allocation
- Randomised
- Model
- Parallel groups
- Purpose
- Treatment
- Masking
- Quadruple masking
- Masked roles
- Participants, Care providers, Investigators, Outcome assessors
Number of Participants With Composite of Stroke or Systemic Embolism
Timeframe: Approximately 12 months
The assessment was based on the cause-specific hazard ratio (csHR), comparing asundexian with apixaban which is based on time to first event. 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. Systemic embolism is defined as abrupt vascular insufficiency associated with clinical or radiological evidence of arterial occlusion in the absence of other likely mechanisms (this does not include myocardial infarction, thromboembolism of the pulmonary vasculature or venous thrombosis, e.g. pulmonary embolism or deep venous thrombosis).
Number of Participants With International Society on Thrombosis and Hemostasis (ISTH) Major Bleeding
Timeframe: Approximately 12 months
Assessment based on the (csHR), comparing asundexian with apixaban which is based on time to first event. ISTH Major Bleeding was defined as an event that meets at least one of the below criteria, based on the definition given by the ISTH (Schulman and Kearon 2005): * Fatal bleeding, and/or * Symptomatic bleeding in a critical area or organ (intracranial, intraspinal, intraocular with compromised vision, pericardial, retroperitoneal, intra-articular, or intramuscular with compartment syndrome), and/or * Clinically overt\* bleeding associated with a recent (within 48 hours) decrease in the hemoglobin level of ≥ 2 g/dL (20 g/L; 1.24 mmol/L) compared with the most recent hemoglobin value available before the event, and/or * Clinically overt\* bleeding leading to transfusion of 2 or more units of packed red blood cells or whole blood. * Overt bleeding required the identification of the bleeding location and the hemoglobin drop and/or transfusion needed to be related to the bleeding.
Number of Participants With Composite of Stroke, Systemic Embolism, or ISTH Major Bleeding
Timeframe: Approximately 12 months
The assessment was based on the cause-specific hazard ratio (csHR), comparing asundexian with apixaban which is based on time to first event.
Number of Participants With Composite of Ischemic Stroke or Systemic Embolism
Timeframe: Approximately 12 months
The assessment was based on the cause-specific hazard ratio (csHR), comparing asundexian with apixaban which is based on time to first event. An ischemic stroke was defined as the rapid onset (or present on awakening) of a new focal neurological deficit with clinical (\> 24 hours symptoms / signs) or imaging evidence of infarction that is not attributable to a non-ischemic cause (i.e. not associated with infection, tumor, seizure, severe metabolic disease).
Number of Participants With All-cause Mortality
Timeframe: Approximately 12 months
The assessment was based on the cause-specific hazard ratio (csHR), comparing asundexian with apixaban which is based on time to first event.
Number of Participants With Ischemic Stroke
Timeframe: Approximately 12 months
The assessment was based on the cause-specific hazard ratio (csHR), comparing asundexian with apixaban which is based on time to first event. An ischemic stroke was defined as the rapid onset (or present on awakening) of a new focal neurological deficit with clinical (\> 24 hours symptoms / signs) or imaging evidence of infarction that is not attributable to a non-ischemic cause (i.e. not associated with infection, tumor, seizure, severe metabolic disease).
Number of Participants With Cardiovascular (CV) Death
Timeframe: Approximately 12 months
The assessment was based on the cause-specific hazard ratio (csHR), comparing asundexian with apixaban which is based on time to first event. CV death included death due to stroke, myocardial infarction, heart failure or cardiogenic shock, sudden death or any other death due to other cardiovascular causes or CV procedures. In addition, death due to non-traumatic cardiovascular hemorrhage will be included, e.g. non-stroke intracranial hemorrhage, non-procedural or non-traumatic vascular rupture (e.g. aortic aneurysm), or hemorrhage causing cardiac tamponade
Number of Participants With Composite of CV Death, Stroke, or Myocardial Infarction (MI)
Timeframe: Approximately 12 months
The assessment was based on the cause-specific hazard ratio (csHR), comparing asundexian with apixaban which is based on time to first event. The diagnosis of MI requires the combination of: * Presence of acute myocardial injury (changes in cardiac biomarkers) and * 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.
Number of Participants With Composite of ISTH Major or Clinically Relevant Non-major Bleeding
Timeframe: Approximately 12 months
The assessment was based on the cause-specific hazard ratio (csHR), comparing asundexian with apixaban which is based on time to first event. Clinically relevant non-major bleeding was considered any sign or symptom of acute or sub-acute clinically overt bleeding that does not fit the criteria for the ISTH definition of major bleeding, but does meet at least one of the following criteria (based on criteria published by the EMA) (EMA 2014): * requiring medical or surgical treatment by a healthcare professional for bleeding * leading to hospitalization or increased level of care for bleeding * a change in antithrombotic therapy (including study intervention) for bleeding \*Overt bleeding required the identification of the bleeding location.
Number of Participants With Clinically Relevant Non-major Bleeding
Timeframe: Approximately 12 months
The assessment was based on the cause-specific hazard ratio (csHR), comparing asundexian with apixaban which is based on time to first event.
Number of Participants With Hemorrhagic Stroke
Timeframe: Approximately 12 months
The assessment was based on the cause-specific hazard ratio (csHR), comparing asundexian with apixaban which is based on time to first event. Hemorrhagic stroke was defined as an acute, atraumatic extravasation of blood into the brain parenchyma, intraventricular or subarachnoid space with associated neurological symptoms. This does not include microbleeds or hemorrhagic transformation of an ischemic stroke.
Number of Participants With Intracranial Hemorrhage
Timeframe: Approximately 12 months
The assessment was based on the cause-specific hazard ratio (csHR), comparing asundexian with apixaban which is based on time to first event.
Number of Participants With Fatal Bleeding
Timeframe: Approximately 12 months
The assessment was based on the cause-specific hazard ratio (csHR), comparing asundexian with apixaban which is based on time to first event.
Number of Participants With Minor Bleeding
Timeframe: Approximately 12 months
The assessment was based on the cause-specific hazard ratio (csHR), comparing asundexian with apixaban which is based on time to first event. All other overt bleeding episodes not meeting the criteria for ISTH major or clinically relevant non-major bleeding were classified as minor bleeding (for example, bleeding from a minor wound that does not prompt a treatment for the bleeding, for instance with surgical hemostasis, or epistaxis that does not require a medical treatment for bleeding or a change in antithrombotic therapy).
Number of Participants With Composite of Stroke, Systemic Embolism, ISTH Major Bleeding, or All-cause Mortality
Timeframe: Approximately 12 months
The assessment was based on the cause-specific hazard ratio (csHR), comparing asundexian with apixaban which is based on time to first event.
Number of Participants With Composite of Disabling Stroke (mRS ≥ 3), Critical Bleeding, or All-cause Mortality
Timeframe: Approximately 12 months
The assessment was based on the cause-specific hazard ratio (csHR), comparing asundexian with apixaban which is based on time to first event. Critical bleeding was defined as symptomatic bleeding in either of the following critical locations (intracranial, intraspinal, pericardial, intra-articular, or retroperitoneal) or as intraocular bleeding with compromised vision or intramuscular bleeding with compartment syndrome.
- Sex
- All
- Age groups
- Adults, Older adults
- Minimum age
- 18 Years
- Healthy volunteers
- No
-
18 years of age or older
-
The patient willing and able to understand the Patient information Sheet and provide written informed consent
-
Atrial fibrillation with an indication for indefinite treatment with an oral anticoagulant
-
CHA2DS2-VASc score ≥ 3 if male or ≥ 4 if female, OR CHA2DS2-VASc score of 2 if male or 3 if female and at least one of the following enrichment criteria:
- age ≥ 70
- previous stroke, transient ischemic attack, or systemic embolism
- renal dysfunction with eGFR < 50 ml/min within 14 days prior to randomization
- prior episode of non-traumatic major bleeding
- current single agent antiplatelet therapy planned to continue for at least 6 months after randomization
- ≤ 6 consecutive weeks of treatment with oral anticoagulant prior to randomization.
-
Mechanical heart valve prosthesis
-
Moderate-to-severe mitral stenosis at the time of study inclusion.
-
Atrial fibrillation only due to reversible cause.
-
Participants after successful ablation therapy without documented recurrent AF or participants after left atrial appendage occlusion / exclusion or plan for ablation or Left atrial appendage (LAA) occlusion / exclusion within the next 6 months.
-
Recent ischemic stroke (within 7 days prior to randomization).
-
Active non-trivial bleeding; known chronic bleeding disorder ; history of non-traumatic intracranial hemorrhage.
-
Known significant liver disease or known hepatic insufficiency classified as Child-Pugh B or C at randomization.
-
Estimated glomerular filtration rate (eGFR) < 25 mL/min/1.73 m2 within 14 days prior to randomization or on dialysis or expected to be started on dialysis within the next 12 months starting from randomization.
-
Major surgery during the last 30 days prior to randomization.
-
Known allergy, intolerance or hypersensitivity to either of the study interventions.
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Any contraindication for the use of an anticoagulant or listed in the local labelling for apixaban.
-
Requirement for chronic anticoagulation for a different indication than AF, e.g. mechanical heart valve or left ventricular cardiac thrombus (atrial thrombus is allowed), or dual antiplatelet therapy (single agent therapy is allowed).
-
Treatment with Vitamin K antagonist (VKA) in the 10 days prior to randomization.
-
Concomitant use of or anticipated need for:
- daily or near daily (> 5 days per week) therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) for more than 4 weeks during the study
- herbal or traditional medicine, and / or supplements with known anticoagulant and / or antiplatelet effect
- combined P-glycoprotein (P-gp) and strong cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitors
- combined P-gp and strong / moderate CYP3A4 inducers Respective substances (apart from NSAIDs) must be stopped - in case of combined inhibitors / inducers of CYP3A4 and P-gp for at least 14 days before randomization.
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Previous (within 30 days or 5 half-lives of the investigational drug, whichever is longer) or concomitant participation in another clinical study with investigational medicinal product(s) or device(s). Registries and observational studies are allowed.
-
Known current alcohol and / or illicit drug abuse.
-
Close affiliation with the investigational site.
-
Any other history, condition or therapy, or uncontrolled intercurrent illness which would make the participant unsuitable for the study vulnerable or life expectancy < 12 months.
- SEC Clinical ResearchDothan, United States
- Eastern Shore Research Institute, LLC | Fairhope, ALFairhope, United States
- Mobile Heart Specialists, PCMobile, United States
- University of South Alabama Medical CenterMobile, United States
- Arkansas Cardiology | Little RockLittle Rock, United States
- Valley Clinical Trials, Inc. | Covina, CACovina, United States
- Science 37Culver City, United States
- University of California, IrvineIrvine, United States
- VA Long Beach Healthcare SystemLong Beach, United States
- VA Greater Los Angeles Healthcare System | West Los Angeles VA Medical Center - Cardiology DepartmentLos Angeles, United States
- Radin Cardiovascular Medical GroupNewport Beach, United States
- Amicis Research Center | Northridge, CANorthridge, United States
- Cottage Health | Santa Barbara Cottage Hospital - Cardiology DepartmentSanta Barbara, United States
- NorthBay Clinical Research, LLC | Santa Rosa, CASanta Rosa, United States
- The Lundquist Institute | Cardiology DepartmentTorrance, United States
- Harbor - UCLA Medical CenterTorrance, United States
- Blue Coast Research Center, LLCVista, United States
- Interventional Cardiology Medical Group | West Hills, CAWest Hills, United States
- University of Colorado Hospital - CardiologyAurora, United States
- South Denver Cardiology Associates, PCLittleton, United States
- Cardiology Associates of Fairfield County, P.C. | Stamford, CTNorwalk, United States
- Integrity Clinical Research | Florida Premier CardiologyBoynton Beach, United States
- Integrity Clinical Research | Cardiology Associates of South FloridaBoynton Beach, United States
- Cardiovascular & Vein Center of Florida | Bradenton, FLBradenton, United States
- Nova Clinical Research | Brandenton, FLBradenton, United States
And 1,044 more, listed on the interactive page.
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