Stroke, Vol 24, 1000-1004, Copyright © 1993 by American Heart Association
EC Haley Jr, TG Brott, GL Sheppard, W Barsan, J Broderick, JR Marler, GL Kongable, J Spilker, S Massey and CA Hansen
BACKGROUND AND PURPOSE: Early thrombolytic therapy with recombinant
tissue-type plasminogen activator is a theoretically attractive approach to
the treatment of acute focal cerebral ischemia. In preparation for a larger
multicenter trial, three centers piloted a protocol for a randomized,
double-blind, placebo-controlled trial of intravenous recombinant
tissue-type plasminogen activator begun within 3 hours of the onset of
symptoms of acute stroke to test its feasibility and to explore trends.
METHODS: Eligible patients had pretreatment computed tomographic scanning,
gave informed consent, and began treatment with either 0.85 mg/kg
recombinant tissue-type plasminogen activator or placebo as soon as
possible, but no later than 180 minutes after stroke onset. Patients were
stratified by whether treatment was begun within 90 minutes or 91 to 180
minutes from onset. The primary end point was the proportion of patients in
each group who improved by 4 or more points on the National Institutes of
Health Stroke Scale at 24 hours, as determined by a separate blinded
evaluator. RESULTS: Twenty-seven patients were randomized: 20 (10
recombinant tissue-type plasminogen activator, 10 placebo) within 90
minutes, and 7 (4 recombinant tissue-type plasminogen activator, 3 placebo)
from 91 to 180 minutes. Median baseline Stroke Scale scores were 16
(minimum = 5, maximum = 26) for the recombinant tissue-type plasminogen
activator-treated group and 11 (minimum = 3, maximum = 21) for the control
subjects in the group treated within 90 minutes. Six patients treated with
recombinant tissue-type plasminogen activator within 90 minutes improved by
4 or more points at 24 hours compared with 1 patient in the placebo group
(P < .05, Fisher's Exact Test). Two patients in each group in the 91- to
180-minute arm improved. One fatal intracerebral hemorrhage occurred in the
placebo group. CONCLUSIONS: A randomized, double-blind, placebo-controlled
trial of recombinant tissue-type plasminogen activator very early in acute
stroke is feasible. Preliminary observations suggest that recombinant
tissue-type plasminogen activator treatment within 90 minutes may be
associated with early neurological improvement. Larger studies are needed
so that the potentially serious short-term risks of this treatment can be
assessed in relation to meaningful long-term benefit.
ARTICLES
Pilot randomized trial of tissue plasminogen activator in acute ischemic stroke. The TPA Bridging Study Group
Department of Neurology, University of Virginia School of Medicine, Charlottesville.
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