Ischemic Stroke, Acute
Conditions
Brief summary
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
DRUGMethylprednisolone 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.
DRUGPlacebo
Matched intravenous placebo will be administered for 3 days, with a maximum daily dose of 4 vials.
Sponsors
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The modified Rankin Scale score (mRS) 0-3 | 90±14 days after randomization | The proportion of mRS score 0-3 at 90 (±14) days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The modified Rankin Scale score (mRS) 0-1 | 90±14 days after randomization | The proportion of mRS score 0-1 at 90 (±14) days |
| Neurologic deficit (NIHSS score) changes | 7±1 days after randomization/at discharge | National Institutes of Health Stroke Scale (NIHSS) score change from baseline, at 7 (±1) days or at discharge |
| Infarct core volume changes | 7±1 days after randomization/at discharge or at 36±12 hours after randomization | Infarct core volume change from baseline, assessed with NCCT at 7±1 days after randomization/at discharge or with MRI at 36±12 hours |
| Rate of decompressive craniectomy | 7±1 days after randomization | Rate of decompressive craniectomy at 7 (±1) days |
| The distribution of the modified Rankin Scale scores | 90±14 days after randomization | The shift analysis of mRS at 90±14 days (merged 0-1) |
| The modified Rankin Scale score (mRS) 0-4 | 90±14 days after randomization | The proportion of mRS score 0-4 at 90 (±14) days |
| The modified Rankin Scale score (mRS) 0-2 | 90±14 days after randomization | The proportion of mRS score 0-2 at 90 (±14) days |
| Quality of Life (EQ-5D-5L) | 90±14 days after randomization | Quality of life measured by EQ-5D-5L scale score at 90 (±14) days |
Other
| Measure | Time frame | Description |
|---|---|---|
| SAFETY OUTCOME: Any serious adverse events and steroid-related adverse events (hyperglycemia, infection, and gastrointestinal hemorrhage) | 90±14 days after randomization | Safety will be assessed according to common terminology criteria for adverse events (CTCAE) |
| SAFETY OUTCOME: Symptomatic intracranial hemorrhage (sICH) | Within 48 hours after randomization | Symptomatic intracranial hemorrhage (sICH) within 48 hours (according to Heidelberg criteria) |
| SAFETY OUTCOME: Mortality | 90±14 days after randomization | All-cause mortality within 90 days |
Countries
China
Contacts
Primary ContactXinguang Yang
Outcome results
None listed