rhPro-UK in Acute Ischaemic Stroke Within 4.5 Hours of Stroke Onset Trial 2(PROST-2)

Intravenous thrombolysis is the first-line therapy in patients with acute ischemic stroke within 4·5 hours of symptom onset, and recombinant tissue plasminogen activator (alteplase) is the preferred thrombolytic agent for this purpose.RhPro-UK is a specific plasminogen activator. rhPro-UK only acts on occlusive thrombus and has little effect on hemostatic thrombus. In addition, rhPro-UK does not form covalent complexes with protease inhibitors in plasma, so the concentrations of rhpro-UK and protease inhibitors in the blood do not decrease compared with alteplase. Therefore, rhPro-UK therapies have a potential advantage of less systemic bleeding in treated subjects. Data from several previous studies suggest that rhPro-UK is efficacious when used to treat patients with acute myocardial infarction. On April 2, 2011, rhPro-UK injection was approved by the National Medical Products Administration to treat acute myocardial infarction. Since then, rhPro-UK has been widely used to treat myocardial infarction in China.Since 2016, a phase 2 clinical trial was carried to explore the dosing of rhPro-UK in patients with acute ischemic stroke, followed by another study with a sample size of 680 patients to initially validate the efficacy and safety of the proposed dose of 35mg. The results of these studies suggested that rhPro-UK was effective, and there were no safety concerns. To further prove the efficacy and safety of rhPro-UK in patients with acute ischemic stroke, investigators conducted this phase 3 study (PROST-2).

Inclusion Criteria:Clinically diagnosed as acute ischemic stroke (according to the Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2018).18 years or older, male or female.NIH Stroke Scale（NIHSS）scores of 4 to 25.Treatment within 4.5 hours after stroke onset.The symptoms of stroke last at least 30 minutes without significant improvement before treatment.Informed consent by patient or by patient's guardians.Exclusion Criteria:Prestroke modified rankin scale of ≥2.Large areas of hypodense ischaemic changes on baseline CT（Infarction area> 1/3 of the middle cerebral artery feeding area）.Intracranial hemorrhage.Previous history of intracranial hemorrhage.Severe cerebral trauma or stroke history within 3 months.Intracranial tumor or giant intracranial aneurysm.Intracranial or intraspinal surgery within the past 3 months.Gastrointestinal or urinary bleeding within the past 3 weeks.History of major surgical procedures or severe trauma within the last 2 weeks (investigator evaluation).Puncture in 1 week which can not be oppressed.Active visceral hemorrhage.Aortic arch dissection.Bacterial endocarditis or pericarditis.Planned for thrombectomy.Patients with systolic blood pressure ≥ 185 mmHg or diastolic blood pressure ≥ 110 mmHg after anti-hypertension treatment.High risk of acute hemorrhage include platelet count<10^9/L.Received low molecular weight heparin or heparin within 24 hours.Using of thrombin inhibitors or factor Xa inhibitor within the past 48 hours.Using of oral anticoagulant drugs and PT >15s or INR >1.7.Patients with epilepsy or other mental disorders that could not be adhered to at the beginning of stroke.Blood glucose < 2.8 mmol/L or > 22.2 mmol/L.Allergies to rhPro-UK or rt-PA active ingredients or other components.Pregnant women or beastfeeding women.Participants in other clinical trials within the past month.The investigator believes that the patient is not suitable for the study.