Stroke, Vol 23, 641-645, Copyright © 1992 by American Heart Association
EC Haley Jr, DE Levy, TG Brott, GL Sheppard, MC Wong, GL Kongable, JC Torner and JR Marler
BACKGROUND AND PURPOSE: Renewed interest in thrombolytic therapy as
potential treatment for patients with acute ischemic stroke prompted a
dose-escalation safety study of tissue plasminogen activator in patients
with very early (less than or equal to 90 minutes; see Part I) neurological
symptoms. To test whether this stringent entry window might be safely
lengthened, a second study was organized to test tissue plasminogen
activator in patients with symptoms of 91-180 minutes' duration before
treatment. METHODS: An open-label, dose-escalation design was chosen.
Eligible patients had pretreatment head computerized tomographic scanning
and treatment begun 91-180 minutes from stroke onset. End points examined
included the incidence of symptomatic and asymptomatic intracranial
hemorrhage, other bleeding, and clinical outcome at 2 hours, 24 hours, and
3 months after treatment. RESULTS: Twenty patients were treated at three
hospitals in 13 months. Three doses were tested: 0.6 mg/kg (n = 8), 0.85
mg/kg (n = 6), and 0.95 mg/kg (n = 6). Two patients, one each at the two
highest doses, sustained fatal intracerebral hemorrhages. Three patients
(15%) improved by greater than or equal to 4 points on the National
Institutes of Health Stroke Scale by 24 hours. CONCLUSIONS: These
observations suggest that tissue plasminogen activator treatment of acute
ischemic stroke 91-180 minutes from onset in doses of greater than or equal
to 0.85 mg/kg is attended by a risk of intracerebral hemorrhage
approximating 17% (range 3-44%, 95% confidence interval). The rate of early
neurological improvement observed in this study was small but does not
exclude an improvement over the natural history. Future study with placebo
control subjects and stratification by time to treatment is indicated.
ARTICLES
Urgent therapy for stroke. Part II. Pilot study of tissue plasminogen activator administered 91-180 minutes from onset
Department of Neurology, University of Virginia School of Medicine, Charlottesville 22908.
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