Argatroban Stroke Treatment - A Pilot Safety Study

Ischemic Stroke Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00268762
• Other study ID #: Argatroban+TPA 02-121B
• Secondary ID: P50NS44227 proje
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: December 20, 2005
• Last updated: November 3, 2014
• Start date: February 2003
• Est. completion date: August 2010

Study information

• Verified date: November 2014
• Source: The University of Texas Health Science Center, Houston
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: August 2010
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ischemic Stroke
• Stroke

Intervention

Drug:
• argatroban
Argatroban IV Infusion at 1mcg/kg/min for 48 hours.

Locations

Country	Name	City	State
United States	University of Alabama-Birmingham	Birmingham	Alabama
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	Cedars-Sinai Medical Center	Los Angeles	California
United States	Tulane University	New Orleans	Louisiana

Sponsors (1)

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

Country where clinical trial is conducted

United States, 

References & Publications (2)

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 tis — View Citation

Sugg RM, Pary JK, Uchino K, Baraniuk S, Shaltoni HM, Gonzales NR, Mikulik R, Garami Z, Shaw SG, Matherne DE, Moyé LA, Alexandrov AV, Grotta JC. Argatroban tPA stroke study: study design and results in the first treated cohort. Arch Neurol. 2006 Aug;63(8): — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Symptomatic and Radiographic Intracerebral Hemorrhage	Significant intracerebral hemorrhage as defined by either: Symptomatic intracerebral hemorrhage or; Parenchymal hematoma type 2.	Within 7 days of enrollment	Yes
Secondary	Arterial Complete Recanalization at 2 Hours Post tPA Bolus	Complete Recanalization as measured by either transcranial Doppler Ultrasound at 2 hours post tPA bolus.	2 hours complete recanalization post tPA bolus	No
Secondary	Arterial Complete Recanalization at 24 Hours Post tPA Bolus	Complete recanalization at 24 hours post tPA bolus as measured by either transcranial Doppler ultrasound or CT-Angiography.	24 hours from tPA bolus	No

External Links

•   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.