Single Bolus Non-immunogenic Staphylokinase in Patients With Acute Ischemic Stroke Within 4.5-24 Hours of Symptom Onset

Multicenter, double-blind, randomized, placebo-controlled phase III clinical trial. At the clinical sites, patients with acute ischemic stroke within 4.5-24 hours of symptom onset will be randomized to receive a single bolus injection of the recombinant non-immunogenic staphylokinase (Fortelyzin®, LLC "SuperGene", Russia) or placebo.

Inclusion Criteria: 1. Men and women aged 18 years and over; 2. Acute ischemic stroke symptom onset between 4.5 to 24 hours prior to enrolment, including wake-up stroke and unwitnessed stroke, onset time refers to "last-seen normal time"; 3. Pre-stroke modified Rankin scale (mRS) score≤1; 4. Internal carotid artery, middle cerebral artery M1 or M2 occlusion confirmed by CT/MRI, internal carotid artery, middle cerebral artery M1 or M2 being responsible for signs and symptoms of acute ischemic stroke; 5. Neuroimaging: target mismatch profile on CT or MRI perfusion: ischemic core volume \ 6; 7. Baseline National Institutes of Health Stroke Scale (NIHSS) 6-25 (inclusive); 8. The patient is not planned or cannot undergo thrombectomy or intravenous thrombolysis in accordance with the current version of the Clinical Guidelines; 9. Written informed consent from patients or their legally authorized representatives. Exclusion Criteria: 1. Acute ischemic stroke within 4,5 h after symptom onset; 2. Intended to proceed to endovascular treatment; 3. Known hypersensitivity to the non-immunogenic staphylokinase; 4. Convulsive seizures at the onset of the disease, if there is no certainty that the seizure is a clinical manifestation of acute ischemic stroke; 5. Persistent blood pressure elevation (systolic ≥185 mmHg or diastolic ≥110 mmHg), and the inability to reduce systolic blood pressure below 180 mmHg or diastolic blood pressure below 105 mmHg; 6. Blood glucose \22.2 mmol/L (after blood glucose level correction to the specified values, inclusion of the patient in the study is possible); 7. Neuroimaging (CT, MRI) signs of intracranial hemorrhage, brain tumor, arteriovenous malformation, brain abscess, cerebral aneurysm; 8. Subarachnoid hemorrhage; 9. Major bleeding currently or within the past 6 months; 10. Surgery on the brain or spinal cord in the last 2 months; 11. Punctures of non-compressible arteries and veins in the last 7 days; 12. Gastrointestinal or genitourinary bleeding in the last 3 weeks. Confirmed exacerbations of gastric ulcer and duodenal ulcer in the last 3 months; 13. Platelet count below 100,000/mm3; 14. Previous stroke or severe traumatic brain injury within 3 months; 15. Unable to perform CT or MRI; 16. History of hemorrhagic stroke or stroke of unspecified genesis; 17. Multiple arterial occlusion (bilateral MCA occlusion, MCA occlusion accompanied with basilar occlusion); 18. Concomitant use of indirect oral anticoagulants (warfarin) with INR \> 1.7; 19. Taking direct anticoagulants (heparin, heparinoids) in the previous 48 hours with an APTT value above normal; 20. Taking new oral anticoagulants in the previous 48 hours with a thrombin time value above normal and the impossibility of administering the specific antagonist idarucizumab (for dabigatran) or the presence of anti-Xa activity (for rivaroxaban, apixaban and edoxaban). 21. Severe liver disease, including liver failure, liver cirrhosis, portal hypertension (with esophageal varices), active hepatitis; 22. Acute pancreatitis; 23. Bacterial endocarditis, pericarditis; 24. Arterial aneurysms, malformations of arteries and veins. Suspected dissecting aortic aneurysm; 25. Cancer with an increased risk of bleeding; 26. Major surgeries or severe injuries within the last 14 days, minor surgeries or invasive procedures within the last 10 days; 27. Prolonged or traumatic cardiopulmonary resuscitation (more than 2 minutes); 28. Hemorrhagic diathesis, including renal and hepatic failure; 29. Data on bleeding or acute trauma (fracture) at the time of examination; 30. Pregnant women, nursing mothers, or reluctant to use effective contraceptive measures during the period of trial.