ECASS3

Please note:

The results of the ECASS 3 study discussed here represent the latest scientific research and go beyond the licensed indication of alteplase which is approved for use within 3h of ischaemic stroke onset only.

For questions regarding the use of alteplase, please refer to the Prescribing Information valid in your country.

The data presented here are not intended as the sole source of clinical information on this topic. Readers are advised to search other medical sources for all current clinical information.

To access the presentation of the study´s results please go to the
ESO homepage

Or check the online publication on the website of the
New England Journal of Medicine

A brief summary of the ECASS 3 results can be found in the following.

ECASS 3 - The European Cooperative Acute Stroke Study 3

Primary endpoint (ITT - Intention-to-treat population)

Secondary endpoint (ITT - Intention-to-treat population)

Distribution (shift) analysis day 90

Concluding remarks

ECASS 3 - The European Cooperative Acute Stroke Study 3

The objective of this double-blind, parallel-group, placebo controlled study was to evaluate the efficacy and safety of intravenous thrombolysis using recombinant tissue plasminogen activator (rt-PA) administered 3 - 4.5 hours after onset of symptoms in patients with acute ischaemic stroke.

Administration of intravenous tissue plasminogen activator (rt-PA) within the first 3 hours after ischaemic stroke onset improved outcomes in previous trials. A meta-analysis by Hacke W et al. showed already a potential benefit beyond the 3 hour time window.

• Patients were eligible for inclusion if they were 18 to 80 years of age, had received a clinical diagnosis of acute ischaemic stroke, and were able to receive the study drug within 3 to 4.5 hours. A cerebral computer tomographic (CT) scan was required before randomisation to exclude patients who had an intra- cranial haemorrhage or major ischaemic infarction.
• 821 patients in 19 European countries were enroled.
• Out of the randomised groups, 375 patients were treated with 0.9mg rt-PA per kg body weight intravenously (with an upper, limit of 90mg) and 355 patients received placebo.
• Primary endpoint was disability at 90 days, dichotomised as a favourable outcome (a score of 0 or 1 on the modified Rankin scale).
• In this study, a 52.4% favourable outcome for patients in the alteplase group compared to 45.2% in the placebo group was reported (odds ratio, 1.34; 95% confidence interval [CI], 1.02 to 1.76; relative risk, 1.16; 95% CI, 1.01 to 1.34; P=0.04).
• The overall rate of symptomatic intracranial haemorrhage was low with alteplase (2.4%). The risk of sICH is low and comparable to the 3-hour time window
• Even though the rate of intracranial haemorrhage was higher than with placebo (27% vs. 17.6%; P=0.001; for symptomatic intracranial haemorrhage, 2.4% vs. 0.2%; P=0.008), there was no significant difference in the rate of mortality or other severe adverse events (7.7% and 8.4%, respectively; P=0.68).

These findings are consistent with the results from other randomised, controlled trials of thrombolysis in patients with acute ischaemic stroke.

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* Adjusted for prognostic variables; treatment, baseline NIHSS, smoking history, stroke onset to treatment time, and prior hypertension

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*stratified on Cochran–Mantel–Haenszel test,adjusted for baseline NIHSS scores and time-to-treatment onset
^#Method as per Lees et al. N Engl J Med 2006;354:588-600

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Concluding remarks

• While the trial outcome showed that Actilyse® is safe and effective beyond the 3 hour time window, it is currently only licensed for use up to 3 hours, and patients should be treated with alteplase as early as possible to maximise the benefit.
• In the trial, a median door-to-needle time of 1h 25min was observed - in the future, a reduction of door-to-needle time must be achieved to improve patients’ outcomes and well being.
• Having more time does not mean we should be allowed to take more time.

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