Argatroban TPA Stroke Study

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Andrew Barreto, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier:
NCT00268762
First received: December 20, 2005
Last updated: August 20, 2012
Last verified: August 2012
  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 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study To Determine The Safety Of Argatroban Injection In Combination With Rt-PA In Patients With Acute Ischemic Stroke

Resource links provided by NLM:


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 ]

    Significant intracerebral hemorrhage as defined by either:

    1. Symptomatic intracerebral hemorrhage or
    2. Parenchymal hematoma type 2.


Secondary Outcome Measures:
  • Arterial Complete Recanalization at 2 Hours Post tPA Bolus [ Time Frame: 2 hours complete recanalization post tPA bolus ] [ Designated as safety issue: No ]
    Complete Recanalization as measured by either transcranial Doppler Ultrasound at 2 hours post tPA bolus.

  • Arterial Complete Recanalization at 24 Hours Post tPA Bolus [ Time Frame: 24 hours from tPA bolus ] [ Designated as safety issue: No ]
    Complete recanalization at 24 hours post tPA bolus as measured by either transcranial Doppler ultrasound or CT-Angiography.


Enrollment: 65
Study Start Date: February 2003
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intervention
Argatroban IV Infusion 1 mcg/kg/min for 48 hours
Drug: argatroban
Argatroban IV Infusion at 1mcg/kg/min for 48 hours.

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 demonstrating arterial occlusion can also be enrolled. In those patients, a follow-up CTA (24-36 hours) will be performed.

  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*.

  • *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.

(Note: symptom onset time is determined by the timepoint at which the symptoms are known to the patient or those witnessing the patient's condition.)

  • Males and females ages 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 ICA, MCA (M1 or M2), PCA (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 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 (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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00268762

Locations
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 Southwest Hospital
Houston, Texas, United States, 77074
Memorial Hermann Hospital-Medical Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
The University of Texas Health Science Center, Houston
Investigators
Principal Investigator: Andrew D. Barreto, MD The University of Texas Health Science Center, Houston
  More Information

Additional Information:
Publications:
Responsible Party: Andrew Barreto, Assistant Professor - Neurology, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier: NCT00268762     History of Changes
Other Study ID Numbers: ARGATROBAN TPA STROKE STUDY, P50NS44227 project #2
Study First Received: December 20, 2005
Results First Received: August 20, 2012
Last Updated: August 20, 2012
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

Additional relevant MeSH terms:
Ischemia
Stroke
Cerebral Infarction
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Brain Ischemia
Argatroban
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anticoagulants
Hematologic Agents
Therapeutic Uses
Platelet Aggregation Inhibitors

ClinicalTrials.gov processed this record on August 21, 2014