Argatroban TPA Stroke Study

Condition(s) targeted: Acute Ischemic Stroke

Intervention: argatroban (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: The University of Texas Health Science Center, Houston

Official(s) and/or principal investigator(s):
Andrew D. Barreto, MD, Principal Investigator, Affiliation: The University of Texas Health Science Center, Houston

Overall contact:
Andrew D. Barreto, MD, Phone: 713-500-7002, Email: andrew.d.barreto@uth.tmc.edu

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.

Official title: A Pilot Study To Determine The Safety Of Argatroban Injection In Combination With Rt-PA In Patients With Acute Ischemic Stroke

Study design: Allocation: Non-Randomized, Control: Uncontrolled, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Symptomatic and radiographic intracerebral hemorrhage

Secondary outcome: arterial recanalization

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.

Minimum age: 18 Years. Maximum age: 85 Years. Gender(s): Both.

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

Andrew D. Barreto, MD, Phone: 713-500-7002, Email: andrew.d.barreto@uth.tmc.edu

University of Alabama-Birmingham, Birmingham, Alabama 35249, United States; Recruiting
Andrei V. Alexandrov, MD, Phone: 205-975-8569, Email: avalexandrov@att.net
April Sisson, RN, Phone: 205-975-7571, Email: asisson@uab.edu
Andrei V. Alexandrov, MD, Principal Investigator

Cedars-Sinai Medical Center, Los Angeles, California 90048, United States; Recruiting
Partric D Lyden, MD, Phone: 310-423-5166, Email: lydenp@cshs.org
Felice Lin, Phone: 310-248, Ext: 7645, Email: felice.lin@cshs.org
Partric D. Lyden, MD, Principal Investigator

Tulane University, New Orleans, Louisiana 70112, United States; Recruiting
Sheryl Martin-Schild, MD, PhD, Phone: 504-988-0972, Email: smartin2@tulane.edu
Ellen Dauchy, RN, Phone: 504-988-3690, Email: ellendauchy@hcahealthcare.com
Sheryl Martin-Schild, MD, Principal Investigator

University of Texas-Southwestern Dallas, Dallas, Texas 75390, United States; Recruiting
Jessica Lee, MD, Phone: 214-648-7811, Email: jessica.lee@utsouthwestern.edu
April Blair, RN, Phone: 214-648-0363, Email: april.blair@utsouthwestern.edu
Jessica Lee, MD, Principal Investigator
Christina Hall, MD, Sub-Investigator

Memorial Hermann Southwest Hospital, Houston, Texas 77074, United States; Not yet recruiting
Anitha T. Abraham, MD, Email: anitha.abraham@memorialhermann.org
Sandi Shaw, Phone: 713-456-8149, Email: sandi.shaw@memorialhermann.org
Anitha T. Abraham, MD, Principal Investigator

Memorial Hermann Hospital-Medical Center, Houston, Texas 77030, United States; Recruiting
Andrew D. Barreto, MD, Phone: 713-500-7002, Email: andrew.d.barreto@uth.tmc.edu
Loren Shen, RN, Phone: 713-500-7804, Email: loren.shen@uth.tmc.edu
Andrew D. Barreto, MD, Principal Investigator
James C. Grotta, MD, Sub-Investigator
Sean I. Savitz, MD, Sub-Investigator
Nicole R. Gonzales, MD, Sub-Investigator
George A. Lopez, MD, Sub-Investigator

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.

Starting date: February 2003
Last updated: May 21, 2010