Study of the Combination Therapy of Rt-PA and Eptifibatide to Treat Acute Ischemic Stroke (CLEAR-FDR)

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 the rt-PA is begun. * Age: 18 through 85 years (i.e. candidates must have had their 18th birthday, but not had their 86th birthday). * Intravenous rt-PA 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 International Normalized Ratio (INR) \> 1.7. * 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. * Subjects who received Low Molecular Weight heparins (such as Dalteparin, Enoxaparin, Tinzaparin) as deep vein thrombosis (DVT) prophylaxis or in full dose within the previous 24 hours. * Subjects who received heparin or a direct thrombin inhibitor (such as bivalirudin, argatroban, or lepirudin) within 48 hours from screening must have had a normal partial prothrombin time (PTT). * Subjects who received Factor Xa inhibitors (such as fondaparinux) or direct thrombin inhibitors (such as dabigatran) within the last 4 days. * 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. * 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.