Anti-platelet Precision Medicine to Prevent Stroke Early Progression and Recurrence (PRECISE)

Rapid worsening of an existing focal neurological deficit or rapid onset of a new focal neurological deficit (≥ 24 hours) that is clinically judged by the Investigator not to be attributable to non-ischemic etiology.

• Rapid onset of a new focal neurological deficit with clinical or imaging evidence of infarction and not attributable to a non-ischemic etiology (not associated with brain infection, trauma, tumor, seizure, severe metabolic disease, or degenerative neurological disease); or,
• Rapid worsening of an existing focal neurological deficit that is judged by the Investigator to be attributable to a new infarction. Criteria for symptoms attributable to new infarction may include symptoms that persist and are judged by the investigator to be attributable to new infarction, imaging evidence of infarction, or no evidence of a non-ischemic etiology.

Imaging evidence (by CT or MR) of extravascular blood within the area of infarction, and symptoms judged to be related to the hemorrhagic transformation.

Scenarios which may be judged as symptomatic:

• If blood is already present on imaging at presentation, symptoms are out of proportion to what would be expected for the size and location of the infarct at presentation;
• Clinical deterioration, defined by an increase of 4 points or more in the score on the NIHSS or leading to death, occurring after the initial ischemic event, and identified as the result of the hemorrhagic transformation; or
• Mass effect secondary to the hemorrhagic transformation causing symptoms.

Evidence of hemorrhage in the brain parenchyma or extraparenchymal spaces demonstrated by head imaging, surgery, or autopsy, which is not in the same territory of an underlying acute or subacute ischemic stroke, and is judged to be associated with any new neurologic symptoms (including headache) or leading to death.

The diagnosis of MI will be based on an algorithm developed from the Universal Definition of Myocardial Infarction (Circulation 2007 116:2634-2653) that takes into account 5 categories of clinical information from the acute event: rise and/or fall of cardiac biomarkers, ECG abnormalities, clinical setting, imaging evidence, and pathology.

Documented coronary angioplasty, stenting, or bypass surgery for demonstrated or presumed coronary artery disease.

A hemorrhagic event, judged to be nontraumatic, that results in intraocular bleeding causing loss of vision, the need for a transfusion of two or more units of red cells or the equivalent amount of whole blood, or the need for hospitalization or prolongation of existing hospitalization. This may include bleeding events related to surgical procedures but not those related to accidental trauma. Life-threatening hemorrhagic events will be defined as those that are fatal or require use of intravenous inotropic medication to maintain blood pressure, interventional treatment (including surgical, endoscopic or endovascular interventions), or transfusion of four or more units of red cells or the equivalent amount of whole blood. Non-life-threatening hemorrhagic events will be defined as those classified as major hemorrhagic events but not as life-threatening.

All hemorrhagic events leading to interruption of therapy or discontinuation of the study drug but not classifiable as major hemorrhagic events. This may include bleeding events related to surgical procedures but not those related to accidental trauma.

Death due to ischemic stroke, myocardial infarction, sudden cardiac death, arrhythmia, pulmonary embolism, bowel or limb infarction, or any death not readily attributable to a non-ischemic cause.

Death due to intracranial or systemic hemorrhage.

Any adverse event, not belonging to the other outcome event categories, that is fatal or life threatening, is permanently or substantially disabling, requires or prolongs hospitalization, results in a congenital anomaly, or requires intervention to prevent permanent impairment or damage.

A direct comparison between the aspirin alone group and the aspirin plus clopidogrel group for the incidence of 11 outcome variables evaluated by an independent investigator at the primary endpoints will be conducted.