OPtimizing REperfusion by Primary Intra-Arterial ThRomboLysis for Medium Vessel Occlusion

Prior treatment

• Any active or recent bleeding (gastrointestinal, urinary tract bleeding, etc.), or previous parenchymal organ surgery or biopsy in the last 1 month.

Other illness

• Evidence of intracranial hemorrhage.
• Pre-stroke mRS score ≥ 2.
• Severe allergy to contrast agents (non-mild rash allergy) or absolute contraindication to iodine contrast.
• Known genetic or acquired bleeding disposition or anticoagulant factors deficiency.
• Anticipated life expectancy \<6 months due to advanced disease (e.g., malignancy, severe cardiopulmonary disease, etc.).
• Any condition that, in the judgment of the investigator, makes the patient unsuitable for this study or where this study may impose a significant risk to the patient (e.g., inability to understand and/or comply with study procedures and/or follow-up due to psychiatric disorders, cognitive or emotional impairment).

Lab values

• Coagulation disorder with INR \>1.7 or use of new oral anticoagulants within 48 hours prior to symptom onset.
• Platelet count \<50×10\^9/L.
• Known severe renal insufficiency with glomerular filtration rate \<30 ml/min or blood creatinine \>220 μmol/L (2.5 mg/dl).

Other

• Rapidly improving symptoms, in the judgment of the managing clinician that the improvement is likely to result in the patient having an NIHSS score of \<6 at randomization.
• The intervention procedure is unlikely to be completed as assessed by the investigator.
• Suspected cerebral vasculitis, septic embolization, or vascular occlusion due to infective endocarditis.
• Suspected arterial dissection.
• Systolic blood pressure \>185 mmHg or diastolic blood pressure \>110 mmHg, refractory to treatment.
• Radiological confirmed evidence of mass effect or intracranial tumour (except small meningioma).
• Women who are pregnant or breastfeeding.
• Participation in other clinical trials.

• Aged 18 years or older.
• Clinical diagnosis of acute ischemic stroke.
• CT angiography (CTA) or MR angiography (MRA) confirmed primary isolated medium vessel occlusion (i.e. an occlusion of the co-/non-dominant M2, the M3/M4 segment of the MCA, the A1/A2/A3 segment of the ACA, or the P1/P2/P3 segment of the PCA).
• Baseline NIHSS ≥6.
• Treatment (arterial puncture) can be initiated 5.1 Within 6 hours of last known well (LKW) OR 5.2 Within 6 to 24 hours of LKW AND evidence of salvageable brain tissue on CT perfusion or perfusion-diffusion MRI (ischemic core volume \<50mL, hypo-perfused tissue volume to ischemic core volume ratio \>1.4, mismatch volume \>10mL). Hypo-perfused tissue is defined as Tmax \>6s on CT perfusion or perfusion MRI. Ischemic core is defined as rCBF \<30% on CT perfusion or ADC \<620μm2/s on diffusion MRI.
• Signed informed consent.