Phase I trial assesses intravenous urokinase dosing in acute ischemic stroke patients.

BackgroundPrevious evidence supports the efficacy and safety of intravenous urokinase thrombolysis in acute ischemic stroke (AIS), with additional advantages in terms of cost-effectiveness. Existing studies suggest that treatment response may be dose-dependent; however, current dosing practices remain largely empirical and lack standardization based on high-quality evidence. Establishing a weight-based dosing regimen is, therefore, essential to maximize therapeutic benefit and minimize risks.ObjectiveTo determine the maximum tolerated dose (MTD) of urokinase and to develop an optimized weight-adjusted dosing protocol for AIS.MethodsOUTSET is a prospective, single-center, phase I, dose-escalation clinical trial using a weight-based, rolling-six design in patients with AIS. Patients who meet the inclusion criteria will be assigned to one of four dose groups (15,000 IU/kg, 20,000 IU/kg, 25,000 IU/kg and 30,000 IU/kg). Urokinase will be administered intravenously, diluted in 100 mL of normal saline, over a period of 30 min.OutcomesThe primary endpoint is the identification of the MTD based on dose-limiting toxicity events, including symptomatic intracranial hemorrhage, major bleeding, and other significant adverse events.DiscussionThis study offers a structured, weight-based approach to determining the MTD of intravenous urokinase for AIS using a rolling-six dose-escalation design. By addressing the current lack of standardized, body-weight–adjusted dosing protocols, the findings may enhance the clinical safety and efficacy of urokinase thrombolysis. The results are expected to inform future phase II/III trials and support the development of individualized thrombolytic strategies in routine stroke care.Clinical trial registrationClinicalTrials.gov identifier: NCT07047326.