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(Stroke. 2005;36:607.)
© 2005 American Heart Association, Inc.

Original Contributions

A Pilot Dose-Escalation Safety Study of Tenecteplase in Acute Ischemic Stroke

From the Department of Neurology (E.C.H., K.C.J.), University of Virginia Health System, Charlottesville, Va; and the Department of Neuroscience (P.D.L., T.M.H.), University of California at San Diego.

Correspondence to Dr E. Clarke Haley, Jr., Department of Neurology, Box 800394, University of Virginia Health System, Charlottesville, VA 22908, Ph: 434-924-8041, Fax: 434-982-1726, E-mail ech{at}virginia.edu

Background and Purpose— Recombinant tissue-type plasminogen activator (rtPA) is the only approved treatment in acute ischemic stroke. However, intracerebral hemorrhage (ICH) occurs in 6.4% of patients treated with rtPA and limits its use. Tenecteplase (TNK) is a modified form of rtPA, with longer half-life and greater fibrin specificity. Patients after myocardial infarction had fewer systemic hemorrhages when treated with TNK compared with rtPA. This open-label, dose-escalation safety study was conducted to develop initial experience with TNK in the treatment of ischemic stroke.

Methods— Eligible patients were treated with an intravenous bolus infusion of TNK within 3 hours of stroke onset. The dose escalation was conducted in tiers of 25 patients, starting at 0.1 mg/kg, to a planned maximum of 0.6 mg/kg. The primary endpoint was symptomatic intracranial hemorrhage within 36 hours of treatment. All patients were followed-up for 3 months.

Results— Eighty-eight (88) patients were treated in 4 dosing tiers. In the first 3 tiers (0.1, 0.2, 0.4 mg/kg) of 25 patients each, no symptomatic and 2 (8%), 8 (32%), and 7 (28%) asymptomatic ICHs occurred. Enrollment into the fourth tier at 0.5 mg/kg was closed after 2 of 13 patients (15%) had symptomatic and 3 (23%) had asymptomatic ICHs. Overall, modified Rankin scores at 3 months were similar to those of historical controls treated with rtPA and not significantly different between treatment groups.

Conclusions— TNK doses of 0.1 to 0.4 mg/kg are safe in ischemic stroke. Future trials are needed to compare the effect of TNK on neurological outcome and safety as compared with rtPA.

Key Words: ischemic stroke • tenecteplase • tissue plasminogen activator • thrombolytic therapy

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