Date

2025-07-11

Protocol

Protocol changed

Item Changed

Secondary outcome

Previous Version

1. Ischemic stroke: Development of an acute neurologic deficit in conjunction with brain imaging consistent with acute/subacute ischemic stroke. 2. Cardiovascular death: Death related to cardiovascular cause 3. Hemorrhagic stroke: development of an acute neurologic deficit in conjunction with brain imaging consistent with acute/subacute intraparenchymal, intraventricular or subarachnoid hemorrhage 4. Disabling/fatal stroke: Disabling stroke is defined as stroke resulting in a clinical outcome that is associated with a modified Rankin scale of 4 or 5. Fatal stroke is defined as death occurring within 30 days of stroke. 5. Composite of all stroke, myocardial infarction, systemic thromboembolism, or all-cause death: Components of composite outcome (adjudicated) includes stroke (ischemic, hemorrhagic, and undefined stroke, TIA with positive neuroimaging),myocardial infarction, systemic thromboembolism or all-cause death. Incidence rate estimated as number of participants with incident events divided by cumulative at-risk time, where participant is no longer at risk once an incident event occurred 6. Net clinical benefit (composite of stroke, myocardial infarction, cardiovascular death, fatal bleeding, and symptomatic bleeding into a critical organ or area): Net clinical benefit is a composite of stroke, myocardial infarction, cardiovascular death, fatal bleeding, and symptomatic bleeding into a critical organ or area 7. Modified Rankin Scale: mRS as measured at 12 month visit 8. Secondary safety outcome All intracranial hemorrhage (intracerebral hemorrhage, intraventricular hemorrhage, subdural hematoma, subarachnoid hemorrhage): Intracranial hemorrhage as defined by Signs or symptoms associated with an epidural, subdural, subarachnoid, intraparenchymal or intraventricular hemorrhage on computed tomography (CT) or MRI scan, or as demonstrated by surgery or autopsy. 9. Secondary safety outcome Fatal intracranial hemorrhage: Inctracranial hemorrhage defined as Signs or symptoms associated with an epidural, subdural, subarachnoid, intraparenchymal or intraventricular hemorrhage on computed tomography (CT) or MRI scan, or as demonstrated by surgery or autopsy with death occurring within 30 days of stroke 10. Subdural hemorrhage: Subdural hemorrhage as defined as Signs or symptoms associated with a subdural hemorrhage on computed tomography (CT) or MRI scan, or as demonstrated by surgery or autopsy 11. Secondary safety outcome Hospitalization for any cause: Minimum of one overnight stay in hospital. 12. Secondary safety outcome Cardiovascular death: Death related to cardiovascular cause. 13. Secondary safety outcome Hemorrhagic stroke: Development of an acute neurologic deficit in conjunction with brain imaging consistent with acute/subacute intraparenchymal, intraventricular or subarachnoid hemorrhage. 14. Secondary safety outcome Disabling/fatal stroke: Disabling stroke is defined as stroke resulting in a clinical outcome that is associated with a modified Rankin scale of 4 or 5. Fatal stroke is defined as death occurring within 30 days of stroke.

Next Version

1. Ischemic stroke: development of an acute neurologic deficit in conjunction with brain imaging consistent with acute/subacute ischemic stroke. 2. Hemorrhagic stroke: development of an acute neurologic deficit in conjunction with brain imaging consistent with acute/subacute intraparenchymal, intraventricular or subarachnoid hemorrhage. 3. Unspecified stroke: development of an acute neurologic deficit persisting at least 24 hours or resulting in death prior to 24 hours, without confirmation on imaging or other means (e.g., lumbar puncture, neurosurgery, or autopsy). 4. Intracerebral hemorrhage: a neurologic deficit associated with an intraparenchymal or intraventricular hemorrhage on computed tomography (CT) or MRI scan, or as demonstrated by surgery or autopsy. 5. Convexal subarachnoid hemorrhage (cSAH): Non-incidental, non-traumatic and symptomatic isolated acute/subacute cSAH visualized on CT or MRI (as linear sulcal T2-FLAIR hyperintensity with associated hypointensity on T2*-weighted imaging [GRE/SWI]). Chronic cortical superficial siderosis, even if newly detected compared to previous neuroimaging, does not qualify as a cSAH. 6. Fatal stroke: death occurring within 30 days of stroke. 7. Disabling stroke: stroke resulting in a clinical outcome that is associated with a modified Rankin scale of 4 or 5. 8. Myocardial infarction: Defined by presence of at least one of the following a compatible clinical history and characteristic serum enzymes changes with or without electrocardiographic abnormalities; clinical history and serial ST-segment and T-wave changes which are specifically located with respect to the electrocardiographic leads accompanied by elevation of CPK-MB isoenzyme or troponin in serum; the development of large Q-waves on electrocardiography associated with changes in the ST-segments and T-waves in specific and appropriate leads which indicate the location of the infarct, even in the absence of symptoms or abnormalities in serum enzymes; development of discrete, segmental left ventricular systolic wall motion abnormality concurrent with compatible clinical history, electrocardiographic changes or serum enzyme abnormalities; or histopathological evidence of subacute myocardial necrosis. “Silent” myocardial infarction detected by serial ECG changes or troponin elevation without an acute clinical syndrome or new focal wall-motion abnormalities will not be recorded. 9. All-cause mortality: Persistent and irreversible absence of brain or brainstem function. 10. Systemic thromboembolism: emboli to the arterial circulation excluding myocardial infarction and ischemic stroke. 11. Major hemorrhage: Overt bleeding accompanied by one or more of the following - a decrease in the hemoglobin level of ?20 g per liter over a 24-hour period, transfusion of ?2 units of packed red cells, bleeding at a critical site (intracranial, intraspinal, intraocular, pericardial, intraarticular,intramuscular with compartment syndrome, or retroperitoneal), or fatal bleeding. 12. Intracranial hemorrhage: Signs or symptoms associated with an epidural, subdural, subarachnoid, intraparenchymal or intraventricular hemorrhage on computed tomography (CT) or MRI scan, or as demonstrated by surgery or autopsy. 13. Subdural hemorrhage: Signs or symptoms associated with a subdural hemorrhage on computed tomography (CT) or MRI scan, or as demonstrated by surgery or autopsy. 14. Fatal intracranial hemorrhage: Death within 30 days of an intracranial hemorrhage 15. Hospitalization for any cause: Minimum of one overnight stay in hospital