RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED TRIAL OF THROMBOLYTIC THERAPY WITH INTRAVENOUS ALTEPLASE IN ACUTE ISCHEMIC STROKE (ECASS-II)

Background Thrombolysis for acute ischaemic stroke has been investigat ed in several clinical trials, with variable results. We have assessed the safety and efficacy of intravenous thrombolysis with alteplase (0 .9 mg/kg bodyweight) within 6 h of stroke onset. Methods This non-angi ographic, randomised, double-blind, trial enrolled 800 patients in Eur ope, Australia, and New Zealand, Computed tomography was used to exclu de patients with signs of major infarction. Alteplase (n=409) and plac ebo (n=391) were randomly assigned with stratification for time since symptom onset (0-3 h or 3-6 h). The primary endpoint was the modified Rankin scale (mRS) at 90 days, dichotomised for favourable (score 0-1) and unfavourable (score 2-6) outcome. Analyses were by intention to t reat. Findings 165 (40.3%) alteplase-group patients and 143 (36.6%) pl acebo-group patients had favourable mRS outcomes (absolute difference 3.7%, p=0.277). In a post-hoc analysis of mRS scores dichotomised far death or dependency, 222 (54.3%) alteplase-group and 180 (46.0%) place bo-group patients had favourable outcomes (score 0-2; absolute differe nce 8.3%, p=0.024). Treatment differences were similar whether patient s were treated within 3 h or 3-6 h, 85 (10.6%) patients died, with no difference between treatment groups at day 90+/-14 days (43 alteplase, 42 placebo). Symptomatic intracranial haemorrhage occurred in 36 (8.8 %) alteplase-group patients and 13 (3.4%) placebo-group patients. Inte rpretation The results do not confirm a statistical benefit for altepl ase. However, we believe the trend towards efficacy should be interpre ted in the light ui evidence from previous trials. Despite the increas ed risk of intracranial haemorrhage, thrombolysis with alteplase at a dose of 0.9 mg/kg in selected patients may lead to a clinically releva nt improvement in outcome.