Methylprednisolone Sodium Succinate With Endovascular ThRombectomy for Large Ischemic STroke

Official title

Methylprednisolone Sodium Succinate With Endovascular ThRombectomy for Large Ischemic STroke: A Randomized, Double-blind, Placebo-controlled Trial

Overview

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.

Detailed description

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.

Interventions

• Drug Methylprednisolone sodium succinate
  Intravenous methylprednisolone sodium succinate will be administered at a dose of 2 mg/kg/day for 3 days, with a maximum daily dose of 160 mg (4 vials, 40 mg/vial). It is recommended that the initial dose be administered as soon as possible after randomization.
• Drug Placebo
  Matched intravenous placebo will be administered for 3 days, with a maximum daily dose of 4 vials.

Primary outcome measures

• The modified Rankin Scale score (mRS) 0-3 [Time frame: 90±14 days after randomization]

Secondary outcome measures (8)

• The distribution of the modified Rankin Scale scores [Time frame: 90±14 days after randomization]
• The modified Rankin Scale score (mRS) 0-4 [Time frame: 90±14 days after randomization]
• The modified Rankin Scale score (mRS) 0-2 [Time frame: 90±14 days after randomization]
• The modified Rankin Scale score (mRS) 0-1 [Time frame: 90±14 days after randomization]
• Quality of Life (EQ-5D-5L) [Time frame: 90±14 days after randomization]
• Neurologic deficit (NIHSS score) changes [Time frame: 7±1 days after randomization/at discharge]
• Infarct core volume changes [Time frame: 7±1 days after randomization/at discharge or at 36±12 hours after randomization]
• Rate of decompressive craniectomy [Time frame: 7±1 days after randomization]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University — Guangzhou

Identifiers

NCT: NCT07175649 · SYSKY-2025-603-03

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗