Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke (CLEAR Stroke) Trial

Inclusion Criteria: * Patients must have a serious measurable neurological deficit on the NIH Stroke Scale due to focal brain ischemia. * An NIH Stroke Scale score \>5 at the time that intravenous study drug is begun. * Age: 18 through 80 years (i.e. candidates must have had their 18th birthday, but not had their 81st birthday). * Intravenous therapy must be initiated within 3 hours of onset of stroke symptoms. Exclusion Criteria: * History of stroke in the past 3 months. * Previous intra-cranial hemorrhage, neoplasm, subarachnoid hemorrhage, or arterial venous malformation * Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT scan is normal * Hypertension at time of treatment; systolic BP \> 185 or diastolic \> 110 mmHg or aggressive measures to lower blood pressure to below these limits are needed. * Presumed septic embolus * Presumed pericarditis including pericarditis after acute myocardial infarction * Recent (within 30 days) surgery or biopsy of parenchymal organ * Recent (within 30 days) trauma, with internal injuries or ulcerative wounds * Recent (within 90 days) severe head trauma or head trauma with loss of consciousness * Any active or recent (within 30 days) serious systemic hemorrhage * Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; or oral anticoagulant therapy with prothrombin time greater than 15 or INR \> 1.4 * Baseline lab values: positive urine pregnancy test, glucose \< 50 or \> 400 mg/dl, platelets \<100,000 /mm3, Hct \<25 %, or creatinine \> 4 mg/dl * Ongoing renal dialysis, regardless of creatinine * If heparin has been administered within 48 hours, the patient must have a normal partial thromboplastin time (PTT) * Arterial puncture at a non-compressible site or a lumbar puncture in the previous 7 days * Seizure at onset of stroke * Pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations * Other serious, advanced, or terminal illness or any other condition that the investigator feels would pose a significant hazard to the patient if rt-PA or eptifibatide therapy were initiated * Patients whose peripheral venous access is so poor that they are unable to have two standard peripheral Intravenous lines started. * Current participation in another research drug treatment protocol. Patient cannot start another experimental agent until after 90 days * Informed consent is not or cannot be obtained * Any known history of amyloid angiopathy. Exclusion Criteria/CT Scan: * High density lesion consistent with hemorrhage of any degree. * Significant mass effect with midline shift. * Large (more than 1/3 of the middle cerebral artery) regions of clear hypodensity on the baseline CT scan. Sulcal effacement and/or loss of grey-white differentiation alone are not contraindications for treatment.