It is uncertain whether intravenous methylprednisolone improves outcomes for acute anterior circulation large vessel occlusion (LVO) patients with a large infarct core. In this study, the investigators hypothesize that methylprednisolone plus endovascular thrombectomy (EVT) might be superior to EVT alone in patients with evidence of a large infarct volume. The primary objective of the study is to establish the efficacy of methylprednisolone with EVT in patients with acute anterior circulation LVO and a large infarct core.

The PEARL-MERIT is a multicenter, prospective, randomized, double-blind, placebo-controlled trial. A total of 912 patients (aged 18-85 years) within 24 hours of symptom onset of acute ischemic stroke, who have imaging evidence of an occlusion of the intracranial internal carotid artery (ICA) and/or M1/M2 segment of middle cerebral artery (MCA), a large infarct core, and a planned EVT, will be enrolled.

Patients fulfilling all of the inclusion criteria and none of the exclusion criteria will be randomized 1:1 into 2 groups after obtaining informed consent. One group will receive methylprednisolone, the other group will receive placebo. The primary objective is to evaluate the efficacy of methylprednisolone with EVT compared to placebo with EVT in patients with acute ischemic stroke due to anterior circulation LVO and a large infarct core.

Inclusion Criteria:

• Aged 18 to 85 years;
• Clinically diagnosed acute ischemic stroke with screening NIHSS ≥6;
• Time from last known well to randomization ≤24 hours;
• Pre-stroke mRS score of 0-1;
• Occlusion of the responsible vessel confirmed by CT angiography (CTA), magnetic resonance angiography (MRA), or digital subtraction angiography (DSA) in intracranial segment of internal carotid artery (ICA), M1 or M2 segment of middle cerebral artery (MCA), and plan to undergo EVT;
• Alberta Stroke Program Early CT Score (ASPECTS) of 0-5 on NCCT, or ischemic core volume ≥70 mL (defined as regional cerebral blood flow [rCBF] <30% on CT perfusion [CTP] or apparent diffusion coefficient [ADC] <620×10-⁶ mm²/s on MRI);
• Informed consent obtained.

Exclusion Criteria:

• Intracranial hemorrhage on NCCT or MRI;
• Allergy to corticosteroids;
• Allergy to contrast agents;
• Severe infectious disease unsuitable for corticosteroid therapy or concurrent contraindications to corticosteroid treatment;
• Random blood glucose >22.2 mmol/L (400 mg/dL);
• Known hereditary or acquired bleeding diathesis, coagulation factor deficiency, use of warfarin with an international normalized ratio (INR) >1.7, or administration of novel oral anticoagulants within 48 hours of symptom onset;
• Platelet count <90×10⁹/L;
• History of gastrointestinal or urinary tract bleeding within the last month;
• Current participation in another interventional clinical trial;
• Pregnancy or lactating;
• Renal dysfunction with an estimated glomerular filtration rate (eGFR) <30 mL/min or serum creatinine >220 μmol/L (2.5 mg/dL);
• Persistent systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg despite antihypertensive treatment;
• Life expectancy <6 months due to terminal illnesses such as malignancy or severe cardiopulmonary disease;
• Intracranial aneurysm or arteriovenous malformation;
• Intracranial tumour with mass effect on imaging (except for small meningiomas);
• Other conditions deemed unsuitable for study participation by the investigator, including inability to comprehend and/or comply with study procedures and/or follow-up due to psychiatric, cognitive, or emotional disorders.