Abstract 79: Preliminary Efficacy and Safety of Intravenous Recombinant Human Pro-urokinase (rhpro-UK) for Acute Ischemic Stroke:AMulticenter Phase IIa, Randomized, Open, Positive Controlled, Trial(rhpro-UK STROKEIIa)

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Objective: To investigate preliminary efficacy and safety of intravenous recombinant human pro-urokinase (rhpro-UK) in patients with acute ischemic stroke (AIS). Methods: In the 23-center phase IIa, time window stratified, randomized, open, positive controlled, clinical trial, patients within 6 hours after the onset of AIS were stratified into two therapeutic time windows. Patients within 4.5 h were randomized to receive intravenous rhpro-UK 50mg, 35mg, or recombinant tissue plasminogen activator (rt-PA; 0.9 mg/kg, maximum 90 mg). Patients within 4.5-6 h were randomized to receive rhpro-UK 50mg or 35mg. Primary outcome was a modified Rankin scale (mRS) score ≤1at 90 days. Secondary outcome was the treatment response based on ≥ 4-point reduction from the baseline National Institutes of Health stroke scale score at 24 hours after treatment. Safety outcomes included symptomatic intracerebral hemorrhage (sICH), death due to any cause, and other serious adverse events. Results: We enrolled 190 patients (Figure 1A). Within 4.5 h, the proportion of patients with a mRS score ≤1 at 90 days did not differ significantly among groups (57.9%, 55.6% and 52.6%, P=0.92). Similarly, there was no statistical significance among groups in term of treatment response at 24 hours (P=0.85). In the 4.5-6 h time window, the rates of functional independence of rhpro-UK 50mg and 35mg were 59.0% and 69.2% (P=0.34). The proportion of patients with functional response to treatment were 28.2% and 33.3% (P=0.62) (Figure1B, 1C). sICH occurred in one patient in the 50mg rphro-UK group within 4.5 h within 30 days after the intervention. There was no significant difference among the five groups in death and rate of other serious adverse events. Conclusion: As compared with rt-PA, intravenous rhpro-UK at two dose within the 4.5 hours after onset of symptoms showed similar efficacy and safety profiles in patients withAIS. Similarly, these two dose groups did not differ in efficacy and safety between 4.5-6.0 hours.