ReoPro and Retavase to Restore Brain Blood Flow After Stroke

• INCLUSION CRITERIA: Patients may be enrolled in the study only if they meet all of the following criteria:

1. Diagnosis of acute ischemic stroke with onset between 3 and 24 hours prior to plannedstart of study drugs. Acute ischemic stroke is defined as a measurable neurologicaldeficit of sudden onset, presumed secondary to focal cerebral ischemia, and nototherwise attributable to ICH or another disease process. Stroke onset will be definedas the time the patient was last known to be without the new clinical deficit.Patients whose deficits have worsened in the last 24 hours are not eligible if theirfirst symptoms started more than 24 hours before. If the stroke started during sleep,stroke onset will be recorded as the time the patient was last known to be intact. Acareful history is important to determine when the patient was last without thepresenting deficits.

2. Disabling neurological deficit attributable to the acute stroke at the start of studydrugs.

3. NIHSS less than or equal to 16.

4. Evidence on PWI MRI of a perfusion defect corresponding to the acute stroke syndromeof at least 2cm in diameter in both long and short axis in any slice. The PWI will beassessed by relative mean transit time (MTT) images. The MRI evaluation must involveecho planar diffusion weighted imaging, MRA, and MRI perfusion. A normal appearing MRAwith an appropriate perfusion defect is eligible. An apparent stenosis or occlusion onMRA with normal appearing perfusion distally will not be eligible. Poor quality oruninterpretable MRA will not make patient ineligible. Patients who have a normal DWIare eligible.

5. Age 18 - 80 years, inclusive.

EXCLUSION CRITERIA: Patients will be excluded from the study for any of the following reasons: General:

1. Current participation in another study with an investigational drug or device within,prior participation in the present study, or planned participation in anothertherapeutic trial, prior to the final assessment in this trial.

2. Time interval since stroke onset of less than 24 hours impossible to determine withhigh degree of confidence.

3. Symptoms suggestive of subarachnoid hemorrhage, even if CT or MRI scan is negative forhemorrhage.

4. Evidence of acute myocardial infarction defined as having at least two of thefollowing three features: 1.) Chest pain suggestive of cardiac ischemia; 2.) EKGfindings of ST elevation of greater than 0.2 mV in 2 contiguous leads, new onset leftbundle branch block, ST segment depression, or T-wave inversion; 3.) Elevated troponinI

5. Contraindication to MRI scan.

6. Women known to be pregnant, lactating or having a positive or indeterminate pregnancytest.

7. Patients who would refuse blood transfusions if medically indicated. Stroke Related:

8. Neurological deficit that has led to stupor or coma (NIHSS level of consciousnessscore greater than or equal to 2).

9. High clinical suspicion of septic embolus.

10. Minor stroke with non-disabling deficit or rapidly improving neurological symptoms.

11. Baseline NIHSS greater than 16. MRI/CT Related:

12. Evidence of acute or chronic ICH by head CT or MRI.

13. Evidence of microbleed on gradient echo MRI (GRE).

14. CT or MRI evidence of non-vascular cause for the neurological symptoms.

15. Signs of mass effect causing shift of midline structures.

16. Incomplete or uninterpretable DWI and PWI.

17. DWI abnormality larger than approximately one third of the territory of the middlecerebral artery territory by qualitative assessment.

18. Satellite DWI hyperintensity with corresponding hyperintensity on T2 weighted image orFLAIR in a vascular territory different than the index stroke (this is evidence of anew ischemic lesion possibly greater than 24 hours in duration). Safety Related:

19. Persistent hypertension with systolic BP greater than 185 mmHg or diastolic BP greaterthan 110 mmHg (mean of 3 consecutive arm cuff readings over 20-30 minutes), notcontrolled by antihypertensive therapy or requiring nitroprusside for control.

20. Anticipated need for major surgery within 72 hours after start of study drugs, e.g.,carotid endarterectomy, hip fracture repair.

21. Any intracranial surgery, serious head trauma (any head injury that requiredhospitalization), within the past 3 months.

22. Stroke within the past 3 months.

23. History of ICH at any time in the past.

24. Major trauma at the time of stroke, e.g., hip fracture.

25. Blood glucose greater than 200 mg/dl.

26. Presence or history of intracranial neoplasm (except small meningiomas) orarteriovenous malformation.

27. Intracranial aneurysm, unless surgically treated greater than 3 months.

28. Major hemorrhage in past 21 days.

29. Major surgery, serious trauma, lumbar puncture, arterial puncture at anon-compressible site, or biopsy of a parenchymal organ in last 14 days. Majorsurgical procedures include but are not limited to the following: major thoracic orabdominopelvic surgery, neurosurgery, major limb surgery, carotid endarterectomy orother vascular surgery, and organ transplant. For non-listed procedures, the operatingsurgeon should be consulted to assess the risk.

30. Presumed or documented history of vasculitis.

31. Known systemic bleeding disorder, e.g., von Willebrand's disease, hemophilia, others.

32. Platelet count less than 100,000 cells/microL.

33. Congenital or acquired coagulopathy (e.g. secondary to anticoagulants causing eitherof the following:

34. Activated partial thromboplastin time (aPPT) prolongation greater than 2 secondsabove the upper limit of normal for local laboratory, except if due to isolatedfactor XII deficiency. Protamine sulfate reversal of heparin effect does notalleviate this criterion.

35. INR greater than or equal to 1.4. Patients receiving warfarin prior to entry areeligible provided INR is less than 1.4 and warfarin can be safely discontinuedfor at least 48 hours. Potentially Interfering with Outcome Assessment:

36. Life expectancy less than 3 months.

37. Other serious illness, e.g., severe hepatic, cardiac, or renal failure; acutemyocardial infarction; or a complex disease that may confound treatment assessment.

38. Serum creatinine, AST or ALT greater than 3 times the upper limit of normal for thelocal laboratory. Drug Related:

39. Treatment of the qualifying stroke with any thrombolytic or GPIIbIIIa inhibitoroutside of this protocol.

40. Any administration of a thrombolytic drug in the prior 7 days.

41. Treatment of the qualifying stroke with intravenous heparin unless aPTT prolongationis no greater than 2 seconds above the upper limit of normal for local laboratoryprior to study drug initiation.

42. Treatment of the qualifying stroke with a low molecular weight heparinoid.

43. Previous administration of abciximab, if known.

44. Known allergy to murine proteins.

45. Anticoagulation (evidenced by PT, PTT, or platelet count) caused by herbal therapy.