Study of Tenecteplase (TNK) in Acute Ischemic Stroke (TNK-S2B)

Inclusion Criteria: * Patients with at least a serious, measurable deficit on the NIH Stroke Scale in language (aphasia score \> 1), motor power (arm or leg \> 1), vision (best visual score \> 2), or attention (attention score \> 2). Thus eligible patients may have a minimum total score of 1 if the deficit is in language or motor power. There is no maximum score that is exclusionary; even patients with severe hemispheric or brainstem deficits will be eligible, as is current practice with intravenous rt-PA. Patients with all ischemic stroke types and in all vascular distributions are eligible. * Must arrive at participating hospital and treatment begun within 3 hours of the onset of symptoms. Patients awakening with new symptoms must use the time last observed to be normal and awake and the total time cannot exceed three hours prior to treatment as the time of onset. * Must be 18 years of age or older. Exclusion Criteria: * Patients with a) minor stroke symptoms (e.g., sensory loss, ataxia, dysarthria, or facial weakness alone) or b) major symptoms which are rapidly improving by the time of treatment. * Patients for whom a complete NIH Stroke Score cannot be obtained (e.g., intubated patients or complete amputees). * Patients with evidence of intracranial hemorrhage on pretreatment CT scan. * Patients with a clinical presentation that suggests subarachnoid hemorrhage, even if the initial CT scan is normal. * Patients who are known or suspected to be pregnant. * Patients with a known bleeding diathesis or patients with a platelet count \< 100,000. For patients who are taking oral Warfarin (Coumadin), the results of the pretreatment International Normalized Ratio (INR) must be available prior to treatment and must be * \</= 1.4. Patients who have received heparin within 48 hours must have a normal partial thromboplastin time (PTT) to be eligible. Patients who have received low molecular weight heparin or heparinoid within 24 hours are also excluded. * Patients with major surgery or serious trauma excluding head trauma within 14 days or serious head trauma within 3 months. * Patients with a history of gastrointestinal or urinary tract hemorrhage in the previous 21 days. * Patients with an arterial puncture at a non-compressible site or a lumbar puncture in the previous 7 days. * Patients who, on repeated measurement, have a systolic blood pressure \> 185, or a diastolic blood pressure \> 110 mmHg when treatment is to begin, or require aggressive treatment to reduce blood pressure to within these limits. * Patients with a history of stroke in the previous 3 months or have ever had an intracranial hemorrhage considered to put them at increased risk for intracranial hemorrhage. * Patients with a serious medical illness likely to interfere with treatment or treatment might adversely affect that illness. * Patients with abnormal blood glucose thought to account for the neurological deficit. * Patients with a clinical presentation consistent with acute myocardial infarction or patients with presentation suggesting post-myocardial infarction pericarditis. * Patients with a seizure at onset of stroke thought to be presenting with post-ictal paralysis mimicking stroke. * Patients with pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations. * Patients who have received any other investigational drug within 14 days. * Patients who have large areas (greater than one lobe) of obvious low density on the baseline CT scan will be presumed to have had ongoing cerebral ischemia for greater than 3 hours, and will, therefore, be excluded. Patients with subtle early signs of cerebral infarction (e.g., sulcal effacement, blurring of the grey-white junction, asymmetry of the basal ganglia, insular ribbon sign, and others) and the dense artery sign on baseline CT scan will be eligible. Similarly, evidence of previous remote cerebral infarction on baseline CT will not be exclusionary. * Patients for whom informed consent cannot be obtained.