Multi-arm Optimization of Stroke Thrombolysis

Inclusion Criteria:

1. Acute ischemic stroke patients

2. Treated with 0.9mg/kg IV rt-PA within 3 hours of stroke onset or time last known well

3. Age ≥ 18

4. NIHSS score ≥ 6 prior to IV rt-PA

5. Able to receive assigned study drug within 60 minutes of initiation of IV rt-PA

Exclusion Criteria:

1. Known allergy or hypersensitivity to argatroban or eptifibatide

2. Previous stroke in the past 90 days

3. Previous intracranial hemorrhage, neoplasm, subarachnoid hemorrhage, or arterial
venous malformation

4. Clinical presentation suggested a subarachnoid hemorrhage, even if initial CT scan was
normal

5. Surgery or biopsy of parenchymal organ in the past 30 days

6. Trauma with internal injuries or ulcerative wounds in the past 30 days

7. Severe head trauma in the past 90 days

8. Systolic blood pressure >180mmHg post-IV rt-PA

9. Diastolic blood pressure >105mmHg post-IV rt-PA

10. Serious systemic hemorrhage in the past 30 days

11. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency, or
oral anticoagulant therapy with INR >1.5

12. Positive urine pregnancy test for women of child bearing potential

13. Glucose <50 or >400 mg/dl

14. Platelets <100,000/mm3

15. Hematocrit <25 %

16. Elevated PTT above laboratory upper limit of normal

17. Creatinine > 4 mg/dl

18. Ongoing renal dialysis, regardless of creatinine

19. Received Low Molecular Weight heparins (such as Dalteparin, Enoxaparin, Tinzaparin) in
full dose within the previous 24 hours

20. Abnormal PTT within 48 hours prior to randomization after receiving heparin or a
direct thrombin inhibitor (such as bivalirudin, argatroban, dabigatran or lepirudin)

21. Received Factor Xa inhibitors (such as Fondaparinaux, apixaban or rivaroxaban) within
the past 48 hours

22. Received glycoprotein IIb/IIIa inhibitors within the past 14 days

23. Pre-existing neurological or psychiatric disease which confounded the neurological or
functional evaluations e.g., baseline modified Rankin score >3

24. Other serious, advanced, or terminal illness or any other condition that the
investigator felt would pose a significant hazard to the patient if rt-PA,
eptifibatide or argatroban therapy was initiated

a. Example: known cirrhosis or clinically significant hepatic disease

25. Current participation in another research drug treatment protocol - Subjects could not
start another experimental agent until after 90 days

26. Informed consent from the patient or the legally authorized representative was not or
could not be obtained

27. High density lesion consistent with hemorrhage of any degree

28. 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