Intensive Insulin Therapy With Tight Glycemic Control to Improve Outcomes After Endovascular Therapy for Acute Ischemic Stroke

Inclusion Criteria:

1. Age 18-85 years

2. All patients attending the emergency department (ED) of Kaleida health within 24 hrsof symptoms onset suggestive of an anterior circulation ischemic stroke.

3. CT perfusion suggesting Ischemic Core less than 30% of Penumbra territory.

4. No history of diabetes

5. First neurological event

6. Clinical signs consistent with the diagnosis of ischemic stroke, includingimpairment of language, motor function, cognition and/or gaze, vision, or neglect.Ischemic stroke is defined as an event characterized by the sudden onset of a focalneurologic deficit presumed to be due to cerebral ischemia after exclusion of ICHwith a baseline CT

7. The signal stroke should be (a) acute, (b) the most recent significant, acuteworsening of serial neurologic events, or (c) related to a diagnostic radiographicprocedure but not an interventional procedure

8. Minimum NIHSS score >4, except for isolated aphasia or isolated hemianopsia

9. Angiographic evidence of a clot in the anterior intracranial or extracranialcirculation consistent with the neurologic deficit with complete occlusion (TICIgrade 0) or contrast penetration with minimal perfusion (TICI grade 1).

10. Signed informed consent to participate given by patient or legal representative.

Exclusion Criteria:

1. Coma

2. Neurologic signs that are rapidly improving by the time of randomization ortreatment- a 4-point improvement from baseline NIHSS , or increase to absolute NIHSS > 30 before randomization or treatment

3. Major stroke symptoms- NIHSS >30

4. Seizure at the onset of stroke

5. Stroke due to a neurointerventional procedure for treatment of a cerebral aneurysmand/or cerebral arteriovenous malformation (stroke due to diagnostic cerebralangiography or cardiac catheterization might be treated)

6. Clinical presentation suggestive of subarachnoid hemorrhage, even when the initialCT scan is normal.

7. Previous known ICH at any time, neoplasm, and/or subarachnoid hemorrhage.

8. Patients with a known arteriovenous malformation or aneurysm, with or without anyevidence of associated hemorrhage.

9. Presumed septic embolus

10. Known hereditary or acquired hemorrhagic diathesis, eg, aPTT or prothrombin timegreater than normal; unsupported coagulation factor deficiency.

11. Baseline laboratory values that reveal platelets are <30 000/µL, hematocrit orplatelet cell volume <25 volume %, or international normalized ratio >1.7. (Anypatient receiving heparin at the onset of stroke symptoms must have an aPTT 2 timesthe upper limit of normal before randomization. Patients receivinglow-molecular-weight heparin might need to be excluded because an anticoagulanteffect is not measured by aPTT.)

12. Pregnancy, lactation, or parturition within the previous 30 days.

13. Known serious sensitivity to radiographic contrast agents.

14. Other serious, advanced, or terminal illness such that life expectancy is <1 year.

15. Current participation in another research treatment protocol.

16. Previous participation in an acute stroke study.

17. Any condition in which angiography is contraindicated.

18. Uncompensated hypertension at study entry or hypertension requiring aggressivetreatment to reduce blood pressure to non-hypertensive limits. Uncompensatedhypertension is defined as systolic blood pressure >180 mm Hg or diastolic bloodpressure 100 mm Hg on 3 repeated measures at least 10 minutes apart. Aggressivetreatment is defined as the need for a continuous, parenteral antihypertensive, suchas a nitroprusside drip, or the need to administer >3 doses of a parenteralantihypertensive, such as labetalol, hydralazine, nicardepine.

19. Dependency on renal dialysis or known serum creatinine > 2.0mg/dl

20. Serum glucose at admission <80mg/dl

21. All known diabetic patients

22. Random Admission glucose > 200mg/dl

23. High-attenuation lesion on CT consistent with a hemorrhage of any degree in anylocation.

24. Evidence of a significant mass effect with a midline shift due to a large infarct

25. Acute hypodense parenchymal lesion on CT or effacement of the cerebral sulci in morethan one third of the MCA territory or suspected stroke region

26. Angiographic evidence of (a) Suspected carotid arterial dissection. (b) Arterialstenosis as the sole lesion or a high-grade stenosis that does not allow safepassage of a catheter. (b) Any nonatherosclerotic arteriopathy (eg, vasculitis)

27. Mentally incompetent and wards of the state.