Urgent therapy for stroke. Part I. Pilot study of tissue plasminogen activator administered within 90 minutes.
OBJECTIVE
Thrombolytic agents hold theoretical promise as therapy for cerebral infarction. This study was designed to evaluate the safety of tissue plasminogen activator, to accomplish urgent patient treatment, and to estimate potential efficacy of tissue plasminogen activator.


METHODS
Following neurological evaluation and computed tomography of the brain, patients with acute ischemic stroke were evaluated and treated with intravenous tissue plasminogen activator under an open-label, dose-escalation design within 90 minutes from symptom onset. End points examined included symptomatic and asymptomatic intracranial hematoma, systemic hemorrhage, and neurological outcome at 2 hours, 24 hours, and 3 months.


RESULTS
Seventy-four patients were treated within 90 minutes of symptom onset over seven dose tiers of tissue plasminogen activator, ranging from 0.35 mg/kg to 1.08 mg/kg. Intracranial hematoma with associated neurological deterioration occurred in three patients and was related to increasing doses of tissue plasminogen activator (p = 0.045). Intracranial hematoma did not occur in any of the 58 patients treated with less than or equal to 0.85 mg/kg. Major neurological improvement occurred in 22 patients (30%) at 2 hours from the initiation of tissue plasminogen activator and in a total of 34 patients (46%) at 24 hours, but major neurological improvement was not related to increasing doses of tissue plasminogen activator or to stroke type.


CONCLUSIONS
Patients with acute stroke can be evaluated and treated within 90 minutes. Tissue plasminogen activator for acute ischemic infarction is not without risk, but the potential for clinical benefit justifies a randomized clinical trial. To date, differences in hemorrhagic risk or neurological benefit of tissue plasminogen activator for particular ischemic stroke types are not apparent.
Brott
T G
TG
Department of Neurology, University of Cincinnati, Ohio.
Haley
E C
EC
Levy
D E
DE
Barsan
W
W
Broderick
J
J
Sheppard
G L
GL
Spilker
J
J
Kongable
G L
GL
Massey
S
S
Reed
R
R
D000368:Aged; D002533:Cerebral Angiography; D002543:Cerebral Hemorrhage / Q000139:chemically induced; D002561:Cerebrovascular Disorders / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D004185:Disability Evaluation; D004305:Dose-Response Relationship, Drug; D005260:Female; D006406:Hematoma / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009420:Nervous System / Q000503:physiopathology; D011994:Recombinant Proteins; D016019:Survival Analysis; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D014057:Tomography, X-Ray Computed
D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator