Adjunctive Intra-arterial Urokinase after Successful Endovascular Thrombectomy in Patients with Large Vessel Occlusion Stroke (POST-UK): Study Protocol of a Multicenter, Prospective, Randomized, Open-Label, Blinded-Endpoint Trial

Background: Intra-arterial infusion of an adjunctive thrombolytic agent after macrovascular recanalization by endovascular thrombectomy (EVT) was regarded as a promising strategy to promote outcomes of stroke patients. Given the characteristics of urokinase (UK) as an affordable, available, and widely applied medication, especially in eastern countries, this trial aims to assess the safety and efficacy of intra-arterial UK as adjunct to EVT in improving outcomes among patients with anterior large vessel occlusion stroke after excellent to complete reperfusion. Methods: The Adjunctive Intra-arterial Urokinase after Successful Endovascular Thrombectomy in Patients with Large Vessel Occlusion Stroke (POST-UK) trial is a multicenter, prospective, randomized, open-label, blinded-endpoint trial conducted in China. The planned sample size is 498. Those eligible patients with anterior circulation large vessel occlusion stroke and achieving excellent to complete reperfusion by EVT are planned to be consecutively randomized in a 1:1 ratio to the experimental group (a single dose of intra-arterial urokinase) or to standard of care. Results: The primary outcome is a freedom from disability (modified Rankin Scale, mRS, of 0-1) at 90±7 days. The safety outcomes are mortality within 90±7 days and symptomatic intracranial hemorrhage within 48 hours. Conclusions: The POST-UK trial will provide valuable insight of efficacy and safety of intra-arterial UK in patients with large vessel occlusion stroke after achieving excellent to complete reperfusion by EVT. ### Competing Interest Statement JLS reports consulting fees for advising on rigorous and safe clinical trial design and conduct from Biogen, Boehringer Ingelheim, Genentech, Johnson&Johnson, Phenox, Phillips, Rapid Medical, and Roche. There are no competing interests for the other authors. ### Clinical Trial ChiCTR2200065617 (www.chictr.org.cn). ### Funding Statement This clinical trial is sponsored by (1) National Natural Science Foundation of China (No. 82271349, 82001264, 82071323), (2) Natural Science Foundation of Chongqing (No. CSTB2024NSCQ-MSX0359), (3) Chongqing Technology Innovation and Application Development Project (No. CSTB2022TIAD-KPX0160), and (4) China Postdoctoral Science Foundation (No. 2023M740444). The study drug was provided by Wuhan Humanwell Pharmaceutical Co.,Ltd., Wuhan, China. The sponsors had no role in the study design, data collection, analysis, interpretation, drafting or submission of this article. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Human Research Ethics Committee of The Second Affiliated Hospital of Chongqing Medical University, and all participating centers I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data that support the findings of this study are available on request from the corresponding author, upon reasonable request.