Multi-arm Optimization of Stroke Thrombolysis

Inclusion criteria

• Acute ischemic stroke patients
• Treated with 0.9mg/kg IV rt-PA or 0.25mg/kg IV TNK within 3 hours of stroke onset or time last known well
• Age ≥ 18
• NIHSS score ≥ 6 prior to IV thrombolysis
• Able to receive assigned study drug within 60 minutes but no later than 75 minutes of initiation of IV thrombolysis

Exclusion criteria

• Known allergy or hypersensitivity to argatroban or eptifibatide
• Previous stroke in the past 90 days
• Previous intracranial hemorrhage, neoplasm, subarachnoid hemorrhage, or arterial venous malformation
• Clinical presentation suggested a subarachnoid hemorrhage, even if initial CT scan was normal
• Any surgery, or biopsy of parenchymal organ in the past 30 days
• Trauma with internal injuries or ulcerative wounds in the past 30 days
• Severe head trauma in the past 90 days
• Systolic blood pressure persistently >180mmHg post-IV thrombolysis despite antihypertensive intervention
• Diastolic blood pressure persistently >105mmHg post-IV thrombolysis despite antihypertensive intervention
• Serious systemic hemorrhage in the past 30 days
• Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR >1.5
• Positive urine or serum pregnancy test for women of child bearing potential
• Glucose <50 or >400 mg/dl
• Platelets <100,000/mm3
• Hematocrit <25 %
• Elevated pre-thrombolysis PTT above laboratory upper limit of normal
• Creatinine > 4 mg/dl
• Ongoing renal dialysis, regardless of creatinine
• Received Low Molecular Weight heparins (such as Dalteparin, Enoxaparin, Tinzaparin) in full dose within the previous 24 hours
• Abnormal PTT within 48 hours prior to randomization after receiving heparin or a direct thrombin inhibitor (such as bivalirudin, argatroban, dabigatran or lepirudin)
• Received Factor Xa inhibitors (such as Fondaparinaux, apixaban or rivaroxaban) within the past 48 hours
• Received glycoprotein IIb/IIIa inhibitors within the past 14 days
• Pre-existing neurological or psychiatric disease which confounded the neurological or functional evaluations e.g., baseline modified Rankin score >3
• 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, TNK, eptifibatide or argatroban therapy was initiated

a. Example: known cirrhosis or clinically significant hepatic disease

• Current participation in another research drug treatment or interventional device trial - Subjects could not start another experimental agent until after 90 days
• Informed consent from the patient or the legally authorized representative was not or could not be obtained
• High density lesion consistent with hemorrhage of any degree
• 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