ECASS-III
ECASS-III: Placebo controlled trial of alteplase (rt-PA) in acute ischemic hemispheric stroke where thrombolysis is initiated between 3 and 4 hours after stroke onset
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Purpose:
To evaluate efficacy and safety of rt-PA between 3 and 4 hours after stroke onset in European setting.
Location(s):
Various European locations
Year Started:
2003
Year Finished:
2008
Year Presented:
2008
Design:
Multicenter, randomized, double blind, placebo controlled trial in 110 hospitals in 15 European countries.
Inclusion Criteria
Male and female stroke patients, aged 18-80 years.
Exclusion Criteria
NIHSS < 25 on admission, ordinary contraindications for thrombolysis, evidence of ICH on admission CT, prior clinical stroke or concomitant diabetes.
Patient Involvement:
Patients will be randomized 1:1 to receive intravenous rt-PA (alteplase 0.9mg/kg bodyweight, maximally 90mg; 10% bolus plus one hour infusion) or placebo started between 3 and 4 hours from the onset of stroke.
Primary Outcome:
Primary efficacy endpoint is Modified Rankin Scale 0-1 at 90 days.
Safety Endpoints: Survival at day 90, stroke related neurological deaths, symptomatic cerebral hemorrhage, cerebral herniation and symptomatic brain edema, vital signs, adverse events, laboratory parameters.
Secondary Outcome:
Secondary efficacy endpoint is Global Outcome (Modified Rankin Scale 0-1, Barthel Index 95-100, NIHSS 0-1, Glasgow Outcome Score 0-1) at 90 days.
Further efficacy parameters are ordinary disability and functional scales, infarct size on CT at various time points after stroke onset, Modified Rankin Scale at 90 days stratified by admission NIHSS and length of in-hospital stay.
Results:
We enrolled a total of 821 patients in the study and randomly assigned 418 to the alteplase group and 403 to the placebo group. The median time for the administration of alteplase was 3 hours 59 minutes. More patients had a favorable outcome with alteplase than with placebo (52.4% vs. 45.2%; odds ratio, 1.34; 95% confidence interval [CI], 1.02 to 1.76; P=0.04). In the global analysis, the outcome was also improved with alteplase as compared with placebo (odds ratio, 1.28; 95% CI, 1.00 to 1.65; P<0.05). The incidence of intracranial hemorrhage was higher with alteplase than with placebo (for any intracranial hemorrhage, 27.0% vs. 17.6%; P=0.001; for symptomatic intracranial hemorrhage, 2.4% vs. 0.2%; P=0.008). Mortality did not differ significantly between the alteplase and placebo groups (7.7% and 8.4%, respectively; P=0.68). There was no significant difference in the rate of other serious adverse events.
As compared with placebo, intravenous alteplase administered between 3 and 4.5 hours after the onset of symptoms significantly improved clinical outcomes in patients with acute ischemic stroke; alteplase was more frequently associated with symptomatic intracranial hemorrhage.
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Source of Information:
Presented at the 28th International Stroke Conference (February 2003).
Presented at the 2008 World Stroke Conference (September 2008).
Presented at the 2009 International Stroke Conference (February 2009).
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Web Links and Publications:
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This information last updated on: 7/8/2009
Reviewed on: 07/08/2009.
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