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.
Inclusion Criteria:
- Ischemic stroke symptoms with onset ≤ 3 hours.
- Males and females ages 18-85 years of age.
- A clot causing complete or partial occlusion via TCD in any one of the following
areas: distal ICA, MCA, PCA distal vertebral or basilar occlusions. TCD must be
abnormal prior to the start of Argatroban. For patients without temporal windows, an
abnormal CTA is required for enrollment(TIMI 0 or 1).
- Females of childbearing potential must have a negative serum pregnancy test prior to
the administration of trial medication.
- Signed written informed consent by the patient or the patient's legal representative
and/or guardian.
- Meet criteria for rt-PA therapy.
Exclusion Criteria:
- Evidence of intracranial hemorrhage on baseline CT scan or non-vascular cause of
neurologic deficit.
- 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 mRS ≥ 2.
- CT scan findings of hypoattenuation of the x-ray signal involving at least 2 lobes of
the brain an at least 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 SGOT and 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.
- Patients who, in the judgement of the investigator, need to be on concomitant (i. e,
during the Argatroban infusion) anticoagulants other than Argatroban, including any
form of heparin, UFH, LMWH, defibrinogenating agent, dextran, other direct thrombin
inhibitors or thrombolytic agents, GPIIb/IIIa or warfarin.(Caveat: However, if in
the judgement of the investigator a patient needs to be anticoagulated, but this can
be deferred for 48 hours, then they can be included).
- Currently participating or has participated in any investigational drug or device
study within 30 days before the first dose of study medication.
- Known hypersensitivity to Argatroban or its agents
