Argatroban Stroke Treatment - A Pilot Safety Study

Phase 1

Completed

Conditions: Ischemic Stroke

Interventions: Drug: argatroban

Registration Number: NCT00268762

Lead Sponsor: The University of Texas Health Science Center, Houston

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 65

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Intervention	argatroban	Argatroban IV Infusion 1 mcg/kg/min for 48 hours

Primary Outcome Measures

Name	Time	Method
Symptomatic and Radiographic Intracerebral Hemorrhage	Within 7 days of enrollment	Significant intracerebral hemorrhage as defined by either: 1. Symptomatic intracerebral hemorrhage or 2. Parenchymal hematoma type 2.

Secondary Outcome Measures

Name	Time	Method
Arterial Complete Recanalization at 2 Hours Post tPA Bolus	2 hours complete recanalization post tPA bolus	Complete Recanalization as measured by either transcranial Doppler Ultrasound at 2 hours post tPA bolus.
Arterial Complete Recanalization at 24 Hours Post tPA Bolus	24 hours from tPA bolus	Complete recanalization at 24 hours post tPA bolus as measured by either transcranial Doppler ultrasound or CT-Angiography.

Trial Locations

Locations (6): Cedars-Sinai Medical Center
🇺🇸
Los Angeles, California, United States
University of Alabama-Birmingham
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Birmingham, Alabama, United States
Memorial Hermann Hospital-Medical Center
🇺🇸
Houston, Texas, United States
Memorial Hermann Southwest Hospital
🇺🇸
Houston, Texas, United States
Tulane University
🇺🇸
New Orleans, Louisiana, United States
University of Texas-Southwestern Dallas
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Dallas, Texas, United States