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Argatroban TPA Stroke Study
This study is currently recruiting participants.
Verified by The University of Texas Health Science Center, Houston, December 2008
Sponsored by: The University of Texas Health Science Center, Houston
Information provided by: The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier: NCT00268762
  Purpose

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 Intervention Phase
Acute Ischemic Stroke
Drug: argatroban
Phase I
Phase II

Drug Information available for: Alteplase Tissue-type plasminogen activator Argatroban
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title: A Pilot Study To Determine The Safety Of Argatroban Injection In Combination With rt-PA In Patients With Acute Ischemic Stroke

Further study details as provided by The University of Texas Health Science Center, Houston:

Primary Outcome Measures:
  • Symptomatic and radiographic intracerebral hemorrhage [ Time Frame: Within 7 days of enrollment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • arterial recanalization [ Time Frame: Within 48 hours of treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 65
Study Start Date: February 2003
Estimated Study Completion Date: December 2009
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: argatroban
    IV-argatroban at 1mcg/kg/min infusion
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 control. 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.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ischemic stroke symptoms with onset ≤ 3 hours.
  • Males and females ages 18-25 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.
  • 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 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.
  • Absent temporal windows on TCD.
  • 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 3months 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.
  • Current platelet count< 100,000/mm3
  • Life expectancy <3 months in the opinion of the investigator.
  • Need for concomitant use of 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.
  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00268762

Contacts
Contact: James C, Grotta, MD 713-500-7088 james.c.grotta@uth.tmc.edu
Contact: Mary Jane Hess, RN/BSN 713-500-7078 mary.jane.hess@uth.tmc.edu

Locations
United States, Texas
Memorial Hermann Hospital-Medical Center Recruiting
Houston, Texas, United States, 77030
Contact: James C. Grotta, MD     713-500-7088     james.c.grotta@uth.tmc.edu    
Sponsors and Collaborators
The University of Texas Health Science Center, Houston
Investigators
Principal Investigator: James C, Grotta, MD The University of Texas Health Science Center, Houston
  More Information

Introduction of the staff and facility of the stroke team, explanation of stroke, types of strokes, treatment, risk factors, recovery, clinical trials, and contact information.  This link exits the ClinicalTrials.gov site

Publications of Results:
Responsible Party: University of Texas-Houston Department of Neurology ( James C. Grotta, MD )
Study ID Numbers: ARGATROBAN TPA STROKE STUDY, P50NS44227 project #2
Study First Received: December 20, 2005
Last Updated: December 19, 2008
ClinicalTrials.gov Identifier: NCT00268762  
Health Authority: United States: Food and Drug Administration

Keywords provided by The University of Texas Health Science Center, Houston:
stroke
thrombin inhibition
thrombolysis
bleeding
outcome

Study placed in the following topic categories:
Thrombin
Cerebral Infarction
Stroke
Vascular Diseases
Tissue Plasminogen Activator
Central Nervous System Diseases
Ischemia
Hemorrhage
Brain Diseases
Cerebrovascular Disorders
Argatroban
Brain Ischemia
Brain Infarction
Infarction

Additional relevant MeSH terms:
Anticoagulants
Therapeutic Uses
Hematologic Agents
Nervous System Diseases
Platelet Aggregation Inhibitors
Cardiovascular Diseases
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009