ProUrokinase for Mild Ischemic Cerebrovascular Events (PUMICE)

Prior treatment

• Active internal bleeding or at high risk of bleeding, e.g.: Major surgery, trauma or gastrointestinal or urinary tract haemorrhage within the previous 21 days, or arterial puncture at a non-compressible site within the previous 7 days;
• Ischemic stroke or myocardial infarction in previous 3 months, previous intracranial haemorrhage, severe traumatic brain injury or intracranial or intraspinal operation in previous 3 months, or known intracranial neoplasm (except for neuroectodermal tumors, such as meningiomas), arteriovenous malformation or giant aneurysm;
• Participation in other interventional clinical trials within the previous 3 months.

Other illness

• NIHSS consciousness score 1a \>2, or epileptic seizure, hemiplegia after seizures (Todd's palsy) or combined with other nervous/mental illness unable to cooperate or unwilling to cooperate;
• Any terminal illness such that patient would not be expected to survive more than 1 year
• Acute or past intracerebral hemorrhage (ICH) identified by CT or MRI (including intraparenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/epidural hematoma);
• Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study;

Lab values

• Allergy to rhPro-UK and it's components (human albumin, mannitol);
• Blood glucose \<2.8 or \>22.2 mmol/L (point of care glucose testing is acceptable);
• Any known impairment in coagulation due to comorbid disease or anticoagulant use. If on warfarin, then INR \>1.7 or prothrombin time \>15 seconds; if use of any direct thrombin inhibitors or direct factor Xa inhibitors or new oral anticoagulants (NOAC) during the last 48 hours unless reversal of effect can be achieved with a reversal agent (by idarucizumab) or sensitivity laboratory test values greater than the upper limit of normal (eg, activated partial thromboplastin time (aPTT), international normalized ratio (INR), platelet count, thrombin time (TT), or appropriate factor Xa activity assay); if on any full dose heparin/heparinoid during the last 24 hours or with an elevated aPTT greater than the upper limit of normal;
• Known defect of platelet function or platelet count below 100,000/mm3 (but patients on antiplatelet agents can be included);

Other

• Rapidly improving symptoms at the discretion of the investigator;
• Intended to proceed to endovascular treatment during 90 days (including mechanical thrombectomy, stent insertion or balloon expansion);
• Persistent blood pressure elevation (systolic ≥180 mmHg or diastolic ≥100 mmHg), despite blood pressure lowering treatment;
• Large cerebral infarction (infarct size \> 1/3 MCA territory) on CT or MRI;
• Pregnant women, nursing mothers, or reluctant to agree taking effective contraceptive measures during the period of trial subjects;

• Age ≥18 years, any gender;
• Acute ischemic stroke symptom onset within 4.5 hours prior to enrollment; onset time refers to 'last-seen normal time';
• Pre-stroke mRS score≤ 1;
• Baseline NIHSS ≤ 5 (both included);
• Written informed consent from patients or their legally authorized representatives