Abstract Body: BACKGROUND
Previous trials and meta analyses demonstrated that alteplase was effective in imaging-selected patients between 4.5-9 hours after stroke onset. However, evidence regarding the safety and effectiveness of alteplase in patients beyond 9-hour therapeutic window who present salvageable tissue is still limited.

METHODS
We conducted a multicenter, prospective, randomized, open-label, blinded-outcome trial at 26 stroke centers in China involving patients who had clinical signs of AIS within 4.5-24 hours and salvageable tissue on perfusion imaging. Enrolled patients were 1:1 assigned to the alteplase group and standard-medical-treatment group. The primary outcome was a score of 0 or 1 on the modified Rankin scale, on which scores range from 0 (no symptoms) to 6 (death), at 90 days. The risk ratio for the primary outcome was adjusted for age, clinical severity at baseline and onset-to-randomization time. The key safety outcomes were symptomatic intracerebral hemorrhage within 36 hours and death within 90 days after randomization.

RESULTS
A total of 372 patients were enrolled; 186 were randomly assigned to receive intravenous alteplase and 186 to receive standard medical treatment. Less than 3% patients underwent rescue endovascular thrombectomy (3 in the alteplase group and 7 in the standard-medical-treatment group). The percentage of patients achieving primary outcome was 40.3% in the alteplase group as compared with 26.3% in the standard-treatment group (relative rate, 1.40; 95% confidence interval, 1.05 to 1.87). Mortality at 90 days was 10.8% with alteplase and 10.8% with standard medical treatment, and the incidence of symptomatic intracerebral hemorrhage within 36 hours after randomization was 3.8% and 0.5%, respectively.

CONCLUSIONS
This prospective randomized trial conduced in China found that intravenous alteplase administered between 4.5 and 24 hours after stroke onset in patients with imaging-selected salvageable tissue led to higher proportion of non-disabled functional outcome compared with standard medical treatment, with no safety concerns.