http://stroke.ahajournals.org/content/47/12/2880.abstract?etoc
Abstract
Background and Purpose—The
DIAS-3 trial (Efficacy and Safety Study of Desmoteplase to Treat Acute
Ischemic Stroke [phase 3]) did not demonstrate a significant clinical
benefit of desmoteplase administered 3 to 9 hours after stroke in
patients with major artery occlusion. We present the results of the
prematurely terminated DIAS-4 trial together with a post hoc pooled
analysis of the concomitant DIAS-3, DIAS-4, and DIAS-J (Japan) trials to
better understand the potential risks and benefits of intravenous
desmoteplase for the treatment of ischemic stroke in an extended time
window.
Methods—Ischemic
stroke patients with occlusion/high-grade stenosis in major cerebral
arteries were randomly assigned to intravenous treatment with
desmoteplase (90 μg/kg) or placebo. The primary outcome was modified
Rankin Scale (mRS) score of 0 to 2 at day 90. Safety assessments
included mortality, symptomatic intracranial hemorrhage, and other
serious adverse events.
Results—In
DIAS-4, 52 of 124 (41.9%) desmoteplase-treated and 46 of 128 (35.9%)
placebo-treated patients achieved an mRS score of 0 to 2 (odds ratio,
1.45; 95% confidence interval, 0.79; 2.64; P=0.23) with equal
mortality, frequency of symptomatic intracranial hemorrhage, and other
serious adverse events in both the treatment arms. In the pooled
analysis, mRS score of 0 to 2 was achieved by 184 of 376 (48.9%)
desmoteplase-treated versus 171 of 381 (44.9%) placebo-treated patients
(odds ratio, 1.33; 95% confidence interval, 0.95; 1.85; P=0.096).
Treatment with desmoteplase was safe and increased the recanalization
rate (107/217 [49.3%] versus 85/222 [38.3%]; odds ratio, 1.59; 95%
confidence interval, 1.08–2.35; P=0.019). Recanalization was associated with favorable outcomes (mRS 0–2) at day 90 in both the treatment arms.
Conclusions—Late
treatment with intravenous 90 µg/kg desmoteplase is safe, increases
arterial recanalization, but does not significantly improve functional
outcome at 3 months.
Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00856661.
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