Argatroban Stroke Treatment - A Pilot Safety Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00268762
Recruitment Status : Completed
First Posted : December 22, 2005
Results First Posted : September 19, 2012
Last Update Posted : November 10, 2014
Information provided by (Responsible Party):
Andrew Barreto, 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.

Condition or disease Intervention/treatment Phase
Ischemic Stroke Drug: argatroban Phase 1 Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 65 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study To Determine The Safety Of Argatroban Injection In Combination With Tissue Plasmingen Activator (TPA) In Patients With Acute Ischemic Stroke
Study Start Date : February 2003
Actual Primary Completion Date : August 2010
Actual Study Completion Date : August 2010

Resource links provided by the National Library of Medicine

Drug Information available for: Argatroban

Arm Intervention/treatment
Experimental: Intervention
Argatroban IV Infusion 1 mcg/kg/min for 48 hours
Drug: argatroban
Argatroban IV Infusion at 1mcg/kg/min for 48 hours.

Primary Outcome Measures :
  1. Symptomatic and Radiographic Intracerebral Hemorrhage [ Time Frame: 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 :
  1. Arterial Complete Recanalization at 2 Hours Post tPA Bolus [ Time Frame: 2 hours complete recanalization post tPA bolus ]
    Complete Recanalization as measured by either transcranial Doppler Ultrasound at 2 hours post tPA bolus.

  2. Arterial Complete Recanalization at 24 Hours Post tPA Bolus [ Time Frame: 24 hours from tPA bolus ]
    Complete recanalization at 24 hours post tPA bolus as measured by either transcranial Doppler ultrasound or CT-Angiography.

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00268762

United States, Alabama
University of Alabama-Birmingham
Birmingham, Alabama, United States, 35249
United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
United States, Louisiana
Tulane University
New Orleans, Louisiana, United States, 70112
United States, Texas
University of Texas-Southwestern Dallas
Dallas, Texas, United States, 75390
Memorial Hermann Hospital-Medical Center
Houston, Texas, United States, 77030
Memorial Hermann Southwest Hospital
Houston, Texas, United States, 77074
Sponsors and Collaborators
The University of Texas Health Science Center, Houston
Principal Investigator: Andrew D. Barreto, MD The University of Texas Health Science Center, Houston

Additional Information:
Publications of Results:
Responsible Party: Andrew Barreto, Assistant Professor - Neurology, The University of Texas Health Science Center, Houston Identifier: NCT00268762     History of Changes
Other Study ID Numbers: Argatroban+TPA 02-121B
P50NS44227 project #2 ( Other Grant/Funding Number: P50NS44227 )
First Posted: December 22, 2005    Key Record Dates
Results First Posted: September 19, 2012
Last Update Posted: November 10, 2014
Last Verified: November 2014

Keywords provided by Andrew Barreto, The University of Texas Health Science Center, Houston:
thrombin inhibition

Additional relevant MeSH terms:
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors