Advancing Reperfusion Therapy for Ischemic Stroke (ARTS): Tenecteplase in Medium Vessel Occlusion (MeVO) for Acute Ischemic Stroke

Prior treatment

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

Other illness

• (1)Allergy to tenecteplase;
• (3)NIHSS consciousness score 1a \>2, or epileptic seizure, hemiplegia after seizures (Todd's palsy) or other neurological/mental illness such that the patient is not able to cooperate or unwilling to cooperate;
• (11)Any terminal illness such that the patient would not be expected to survive more than 1 year;
• (14)Acute or past intracerebral hemorrhage (ICH) identified by CT or MRI;

Lab values

• (6)Blood glucose \<2.8 or \>22.2 mmol/L (point of care glucose testing is acceptable);
• (8)Any known impairment in coagulation due to comorbid disease or anticoagulant use. If on warfarin, then INR \>1.7 or prothrombin time \>15 seconds; use of any direct thrombin inhibitors or direct factor Xa inhibitors during the last 48 hours unless reversal of dabigatran can be achieved with idarucizumab; any full dose heparin/heparinoid during the last 24 hours or with an APTT greater than the upper limit of normal;
• (9)Known defect of platelet function or platelet count below 100,000/mm3 (NB patients taking antiplatelet medication can be included);

Other

• (2)Rapidly improving symptoms at the discretion of the investigator;
• (4)Intention to undergo endovascular treatment.
• (5)Persistent blood pressure elevation (systolic ≥185 mmHg or diastolic ≥110 mmHg), despite blood pressure-lowering treatment;
• (12) Unable to perform CTP or PWI;
• (13)Hypodensity in \>1/3 MCA territory on non-contrast CT or hypodensity outside the current perfusion lesion suggesting distal clot migration (secondary MeVO);
• (15)Pregnant women, nursing mothers, or reluctance to use effective contraceptive measures during the period of the trial;
• (16)Unlikely to adhere to the trial protocol or follow-up;

• (1)Age≥18 years old;
• (2)Acute ischemic stroke symptom onset within 4.5 - 24 hours; including wake-up stroke and unwitnessed stroke, onset time refers to "last-seen normal time";
• (3)Primary medium vessel occlusions confirmed by CTA/MRA, including distal M2/M3 segments of the middle cerebral artery (MCA), A1/A2/A3 segments of the anterior cerebral artery (ACA), and P1/P2/P3 segments of the posterior cerebral artery (PCA) and responsible for the signs and symptoms of acute ischemic stroke;
• (4)Neuroimaging criteria: a) Perfusion criteria:Target mismatch profile on CT perfusion or MRI+MR perfusion (ischemic core volume \<70mL, mismatch ratio \>1.2, mismatch volume \>10mL); b) If neither MRI or CT perfusion is available at the site : an Alberta Stroke Program Early CT Score \[ASPECTS\] of 8 or more on NCCT /MRI-DWI or PC-ASPECTS of 8 or more on NCCT/MRI-DWI.
• (5)Pre-stroke modified Rankin scale (mRS) score ≤1;
• (6)Baseline National Institutes of Health Stroke Scale (NIHSS) ≥6 or NIHSS 3-5 with disabling symptoms;
• (7)Written informed consent from patients or their legally authorized representatives.