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ECASS III Trial: Expanded Window for tPA in Stroke

Summary:

  • The ECASS III Trial was a well-designed study that provided further support for the use of tPA for improving the chance of favorable neurologic outcomes at 90 days in those < 80 yrs of age and with diabetes, history of prior stroke, or presenting with severe stroke.
  • However, there was no difference in mortality, likely due to the increased risk of intracerebral hemorrhage (ICH; 27% vs. 17.6%) and symptomatic ICH (2.4% v 0.2%) in those getting tPA.

ECASS III Trial Summary

  • Hacke W et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008;359(13):1317-1329. PubMed
    Level of Evidence 1b
    Study Design Prospective, Multicenter, Randomized, Double-Blind Trial in 19 European countries
    Sample Size N = 821
    Population Adults 18 - 80 yrs of age presenting with acute ischemic stroke within 3 to 4.5 hours of onset
    Exclusion Criteria Intracranial hemorrhage (ICH) or major cerebral infarction giving a NIHSS > 25
    Interventions
    • N = 418 received tPA 0.9 mg/kg 
    • N = 403 received placebo
    Primary Endpoint Disability at 90 days as measured by the modified Rankin scale (0 or 1; meaning no or little disability)
    Secondary Endpoint
    • Combined outcomes at 90 days as measured by Barthel Index, NIHSS, and Glasgow outcomes scale.
    • Mortality
    • Any intracerebral hemorrhage (ICH)
    • Symptomatic ICH
    Results
    • Little to no disability at 90 days was 52.4% with tPA vs. 44.2% with placebo.
    • Patients getting tPA had greater ICH (27% vs 17.6%) and symptomatic ICH (2.4% vs 0.2%) compared to placebo.
    • There was no difference in mortality between tPA and placebo (7.7% for tPA vs 8.4% for placebo, p = 0.68).
    NNT = 14
    Conclusions Despite the higher incidence of ICH, those receiving tPA between 3 to 4.5 hours had favorable neurologic outcomes at 90 days, but no difference in mortality.
    Location 130 centers in 19 European countries
    ClinicalTrials.gov NCT00153036
    Comments The ECASS and ECASS II both investigated the use of tPA up to 6 hours of presentation of symptom onset, but failed to find a favorable neurologic outcome. A meta-analysis published in Lancet 2004 showed a benefit not only a neurologic benefit for patients presenting within 3 hours, but also in those between 3 - 4.5 hrs. This well-designed study further supports the use of tPA for improving neurologic outcomes at 90 days especially in those < 80 yrs of age and with diabetes , history of prior stroke, or presenting with severe stroke.

Related Content

    • Clinical Trial Summary:  The NINDS Trial
    • EBM Focused Topic: Intravenous tPA for Acute Ischemic Stroke
    • EBM Focused Topic: Endovascular Treatment of Acute Ischemic Stroke
    • EBM Focused Topic:  Nimodipine for Aneurysmal Subarachnoid Hemorrhage

MESH Terms & Keywords

  • tPA Alteplase, Acute Ischemic Stroke, Extend Use tPA Alteplase, ECASS III trial