Argatroban Stroke Treatment - A Pilot Safety Study

NCT ID: NCT00268762

Last Updated: 2014-11-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-02-28
• Study Completion Date: 2010-08-31

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.

Conditions

Ischemic Stroke

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intervention

Argatroban IV Infusion 1 mcg/kg/min for 48 hours

Group Type: EXPERIMENTAL

argatroban

Intervention Type: DRUG

Argatroban IV Infusion at 1mcg/kg/min for 48 hours.

Interventions

argatroban

Argatroban IV Infusion at 1mcg/kg/min for 48 hours.

Intervention Type: DRUG

Eligibility 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.
• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role: lead

Responsible Party

Andrew Barreto

Assistant Professor - Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Andrew D. Barreto, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center, Houston

Locations

University of Alabama-Birmingham

Birmingham, Alabama, United States

Cedars-Sinai Medical Center

Los Angeles, California, United States

Tulane University

New Orleans, Louisiana, United States

University of Texas-Southwestern Dallas

Dallas, Texas, United States

Memorial Hermann Hospital-Medical Center

Houston, Texas, United States

Memorial Hermann Southwest Hospital

Houston, Texas, United States

Countries

United States

References

Sugg RM, Pary JK, Uchino K, Baraniuk S, Shaltoni HM, Gonzales NR, Mikulik R, Garami Z, Shaw SG, Matherne DE, Moye LA, Alexandrov AV, Grotta JC. Argatroban tPA stroke study: study design and results in the first treated cohort. Arch Neurol. 2006 Aug;63(8):1057-62. doi: 10.1001/archneur.63.8.1057.

Reference Type: RESULT

PMID: 16908730 (View on PubMed)

Barreto AD, Alexandrov AV, Lyden P, Lee J, Martin-Schild S, Shen L, Wu TC, Sisson A, Pandurengan R, Chen Z, Rahbar MH, Balucani C, Barlinn K, Sugg RM, Garami Z, Tsivgoulis G, Gonzales NR, Savitz SI, Mikulik R, Demchuk AM, Grotta JC. The argatroban and tissue-type plasminogen activator stroke study: final results of a pilot safety study. Stroke. 2012 Mar;43(3):770-5. doi: 10.1161/STROKEAHA.111.625574. Epub 2012 Jan 5.

Reference Type: RESULT

PMID: 22223235 (View on PubMed)

Other Identifiers

P50NS44227 project #2

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

P50NS044227

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Argatroban+TPA 02-121B

Identifier Type: -

Identifier Source: org_study_id