Safety of Intravenous Thrombolysis for Wake-up Stroke

This is an open label, multi-center, safety study of acute treatment with IV alteplase in
ischemic stroke patients who wake-up with their symptoms. The primary outcome of this study
is the frequency of symptomatic hemorrhagic transformation evident within 24 hours of
treatment with IV t-PA. Clinical improvement defined as a decrease in the NIHSS score at 24
hours, 3 days and 90 days and modified Rankin at 3 days and 90 days. For patients that have
CTA and CTP, the incidence of large vessel occlusion will be quantified.

Inclusion Criteria:

- Suspected acute ischemic stroke that occurred during sleep or patients who wake up
with focal neurological symptoms. This includes all patients who were last known to
be neurologically normal the night before,but then found upon awakening with stroke
deficits. It will be considered that the last known onset time is the time when the
patient was last known to be well.

- 18 to 80 years old

- NIHSS ≤25

- BP ≤185 mmHg systolic & ≤110 mmHg diastolic at the time of enrollment. Treatment of
higher systolic BP is permitted, prior to enrollment

- t-PA must be given within 3 hrs of awakening from sleep

- Female patients of child-bearing potential must have a negative pregnancy test
prior to enrollment

Exclusion Criteria:

- CT Exclusion Criteria: Hypodensity >1/3 MCA territory on non-contrast cranial CT scan
or evidence of intracranial or subarachnoid hemorrhage

- Prior ischemic stroke within 3 months of the presenting event

- History of intracranial hemorrhage

- Known secured or unsecured cerebral aneurysm or vascular malformation

- Inability to control systolic BP > 185 mmHg or diastolic BP > 110 mmHg with IV
anti-hypertensive medications

- Known coagulopathy or evidence of active bleeding

- Surgical procedures, biopsy, subclavian venous or arterial puncture, trauma within 14
days of the event

- Gastrointestinal or genitourinary bleeding within 14 days of the event

- Treated with IV heparin within the previous 24 hours & an abnormal PTT

- Oral anticoagulants & an INR >1.7

- Platelet count <100,000

- Venous glucose either <50 or >450

- Any patient who qualifies for this protocol should not be treated with IAT. If the
treating physician believes a patient should undergo IAT, those patients should be
identified a priori and not enrolled into this protocol