Thrombolysis with alteplase 3-4.5 hours after acute ischaemic stroke: the first multicentre, phase III trial in China.

Background and purpose Data on the efficacy and safety of alteplase for acute ischaemic stroke (AIS) administered 3-4.5 hours after the onset of stroke symptoms in Chinese patients is limited. We sought to determine whether AIS patients would benefit from thrombolysis with alteplase between 3 and 4.5 hours after the onset of stroke symptoms in a prospective, multicentre, single-arm trial in China. Materials and methods Eligible AIS patients were given 0.9 mg/kg alteplase intravenously. The primary efficacy endpoint was a favourable outcome at 3 months, defined as a score of 0 or 1 on the modified Rankin Scale. Thresholds for the primary efficacy endpoint were determined to be 40% based on the literature review. The primary safety endpoint was symptomatic intracranial haemorrhage (sICH) according to the European Cooperative Acute Stroke Study III (ECASS III) trial definition. Post hoc analysis between this study and the ECASS III trial were compared using the propensity score matching (PSM) method. Results A total of 120 eligible AIS patients from 11 sites in China received thrombolysis therapy in this study. The median time from onset of symptoms to needle was 3 hours 54 min. The percentage of patients with a favourable outcome was 63.3% (95% CI 54.4 to 71.4), significantly higher than the predefined threshold (p<0.0001). Three patients (2.5%, 95% CI 0.5 to 7.1) had sICH, including two fatal sICH. Six patients died within 3 months after treatment. The post hoc PSM analysis showed a numerically higher rate of the primary efficacy endpoint in this study (63.3%) than the matched placebo arm (56.7%) in the ECASS III trial. Conclusions Intravenous alteplase with a standard dose administered between 3 and 4.5 hours after onset of symptoms is effective and safe for Chinese AIS patients.