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

Prior treatment

• Surgery on the brain or spinal cord in the last 2 months;
• Previous stroke or severe traumatic brain injury within 3 months;
• 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).

Other illness

• Acute ischemic stroke within 4,5 h after symptom onset;
• Known hypersensitivity to the non-immunogenic staphylokinase;
• Convulsive seizures at the onset of the disease, if there is no certainty that the seizure is a clinical manifestation of acute ischemic stroke;
• Neuroimaging (CT, MRI) signs of intracranial hemorrhage, brain tumor, arteriovenous malformation, brain abscess, cerebral aneurysm;
• Subarachnoid hemorrhage;
• Major bleeding currently or within the past 6 months;
• Gastrointestinal or genitourinary bleeding in the last 3 weeks. Confirmed exacerbations of gastric ulcer and duodenal ulcer in the last 3 months;
• History of hemorrhagic stroke or stroke of unspecified genesis;
• Severe liver disease, including liver failure, liver cirrhosis, portal hypertension (with esophageal varices), active hepatitis;
• Cancer with an increased risk of bleeding;
• Hemorrhagic diathesis, including renal and hepatic failure;
• Data on bleeding or acute trauma (fracture) at the time of examination;

Lab values

• Blood glucose \<2.8 or \>22.2 mmol/L (after blood glucose level correction to the specified values, inclusion of the patient in the study is possible);
• Platelet count below 100,000/mm3;
• Concomitant use of indirect oral anticoagulants (warfarin) with INR \> 1.7;
• Taking direct anticoagulants (heparin, heparinoids) in the previous 48 hours with an APTT value above normal;

Other

• Intended to proceed to endovascular treatment;
• 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;
• Punctures of non-compressible arteries and veins in the last 7 days;
• Unable to perform CT or MRI;
• Multiple arterial occlusion (bilateral MCA occlusion, MCA occlusion accompanied with basilar occlusion);
• Acute pancreatitis;
• Bacterial endocarditis, pericarditis;
• Arterial aneurysms, malformations of arteries and veins. Suspected dissecting aortic aneurysm;
• Major surgeries or severe injuries within the last 14 days, minor surgeries or invasive procedures within the last 10 days;
• Prolonged or traumatic cardiopulmonary resuscitation (more than 2 minutes);
• Pregnant women, nursing mothers, or reluctant to use effective contraceptive measures during the period of trial.

• Men and women aged 18 years and over;
• 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";
• Pre-stroke modified Rankin scale (mRS) score≤1;
• 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;
• Neuroimaging: target mismatch profile on CT or MRI perfusion: ischemic core volume \<70 mL, mismatch ratio≥1.8 and mismatch volume≥15 mL;
• Alberta Stroke Program Early CT score (ASPECTS) \> 6;
• Baseline National Institutes of Health Stroke Scale (NIHSS) 6-25 (inclusive);
• The patient is not planned or cannot undergo thrombectomy or intravenous thrombolysis in accordance with the current version of the Clinical Guidelines;
• Written informed consent from patients or their legally authorized representatives.