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.
Minimum age: 18 Years.
Maximum age: 85 Years.
- 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.
- Evidence of intracranial hemorrhage on baseline CT scan or non-vascular cause of
- 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
- 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,
- 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
- Participated in investigational study within 30 days before the first dose of study
- Hypersensitivity to Argatroban or its agents