Argatroban Stroke Treatment - A Pilot Safety Study
Argatroban Stroke Treatment - A Pilot Safety Study
Is the combination of low doses of argatroban in combination with rt-PA safe, and does it
 increase recanalization in patients with acute ischemic stroke.
All patients with acute ischemic stroke who qualify for IV rt-PA under accepted guidelines,
 and who have an occluded middle cerebral artery documented on TCD, receive standard dose IV
 rt-PA and a bolus and 48 hour infusion of argatroban aimed at prolonging the aPTT 1.75 X
 baseline. Follow up CT scanning and TCD every 30 minutes for 2 hours and then daily will
 determine the incidence of hemorrhage, recanalization and reocclusion, and serial
 neurological exam will determine the clinical outcome. For patients without temporal windows,
 a baseline CT-Angiogram (CTA) demonstrating arterial occlusion can also be enrolled. In those
 patients, a follow-up CTA (24-36 hours) will be performed.
Inclusion Criteria:

 -  Ischemic stroke symptoms with onset ≤ 3 hours*.

 -  *or<4.5 hours according to local standard of care. Symptoms must be distinguished
 from another ischemic event such as syncope, seizure, migraine, and hypoglycemia.
 If the patient reports awakening with the event, the time of onset should be
 considered as last time the patient (or a witness to the patient's condition)
 considered herself/himself normal.

 -  18-85 years of age.

 -  A clot causing complete or partial occlusion (TIBI 0, 1, 2, or 3) via TCD in any one
 of the following areas: distal iternal carotid artery (ICA), Meddle cerebral artery
 (MCA - M1 or M2), posterior cerebral arteral (ICA - P1 or P2), distal vertebral or
 basilar occlusions. TCD must be abnormal prior to the start of Argatroban. For
 patients without temporal windows (or in centers without emergent access to TCD), an
 abnormal CTA is required for enrollment (TIMI 0 or 1).

 -  Females of childbearing potential must have a negative serum pregnancy test prior
 administration of argatroban.

 -  Signed informed consent by the patient or the patient's legal representative.

 -  Meet criteria for rt-PA therapy.

 Exclusion Criteria:

 -  Evidence of intracranial hemorrhage on baseline CT scan or non-vascular cause of
 neurologic deficit.

 -  National institute health stroke scale (NIHSS) Level of Consciousness score ≥2.

 -  Baseline (immediately pre-Argatroban) NIHSS ≤ 5 or patient with rapidly resolving
 deficit or rapidly improving symptoms consistent with TPA.

 -  Baseline NIHSS ≥15 for right hemisphere strokes and ≥20 for left hemisphere strokes.

 -  Pre-existing disability with modified rankin scale (mRS) ≥ 2.

 -  CT scan findings of hypoattenuation of the x-ray signal (hypodensity)involving ≥ 1/2
 of the MCA territory.

 -  Any evidence of clinically significant bleeding, or known coagulopathy.

 -  Patients currently on warfarin, with an elevated INR ≥ 1.5.

 -  Patients currently or within previous 48 hrs. on heparin with an elevated aPTT greater
 than the upper limit of normal.

 -  Heparin flush required for an IV line. Line flushes with saline only.

 -  History of ICH or significant bleeding episode within the 3 months before study
 enrollment.

 -  Major surgery or serious trauma within the last 6 weeks.

 -  Patients who have had an arterial puncture at a non-compressible site, biopsy of
 parenchymal organ, or lumbar puncture within the last 2 weeks.

 -  Previous stroke, myocardial infarction, post myocardial infarction pericarditis,
 intracranial surgery, or significant head trauma within 3 months of baseline.

 -  Uncontrolled hypertension.

 -  Alcohol and/or substance abuse that would increase the risk of hemorrhage in the
 opinion of the investigator.

 -  Surgical intervention anticipated within the next 7 days.

 -  Hepatic dysfunction, defined by liver function tests greater than 3 times upper limit
 of normal at baseline, specifically serum glutamic-oxaloacetic transaminase (SGOT) and
 serum glutamic-pyruvic transaminase (SGPT).

 -  Abnormal blood glucose

 -  History of primary or metastatic brain tumor.

 -  Severe mental deficit prior to onset of stroke such as organic brain disorder,
 schizophrenia, etc.

 -  Concurrent severe neurologic disorder, such as seizure at onset of stroke or
 uncontrolled seizure disorder that complicates diagnosis of acute ischemic stroke.

 -  Current platelet count< 100,000/mm3.

 -  Life expectancy <3 months in the opinion of the investigator.

 -  Need to be on concomitant (i.e, during the Argatroban infusion) anticoagulants other
 than Argatroban, including any form of heparin, unfractionated heparin (UFH), low
 molecular weight heparin (LMWH), defibrinogenating agent, dextran, other direct
 thrombin inhibitors or thrombolytic agents, glycoprotein llb/llla (GPIIb/IIIa) or
 warfarin.(Caveat: If these anticoagulants can be deferred for 48 hours, then they can
 be included).

 -  Participated in investigational study within 30 days before the first dose of study
 medication.

 -  Hypersensitivity to Argatroban or its agents