Large Infarct Core, Post-stroke Lymphocytopenia
Conditions
Brief summary
The efficacy and safety of early adjunctive methylprednisolone therapy in acute ischemic stroke patients with large infarct cores (ASPECTS score \< 6) and post-stroke lymphocytopenia remain unclear. These immunocompromised patients face higher mortality rates and poorer clinical outcomes, with limited effective treatment options currently available. This multicenter, randomized, double-blind, placebo-controlled, non-inferiority trial aims to demonstrate that early methylprednisolone administration combined with reperfusion therapy is non-inferior to placebo in terms of survival and functional outcomes at 90 days.
Interventions
DRUGMethylprednisolone sodium succinate
Methylprednisolone sodium succinate Intravenous injection of methylprednisolone sodium succinate (Chongqing Lummy Pharmaceutical Co., Ltd., 40mg/ vial) with a dose of 2mg/kg (maximum dose of 160mg), once daily, for three consecutive days. The initial study drug will be administered as soon as possible after randomization. It is recommended that the initial study drug administrated before arterial access closure, but it should not be delayed more than 2 hours after arterial access closure.
DRUGNormal Saline
Intravenous injection of placebo (normal saline) (Chongqing Lummy Pharmaceutical Co., Ltd., 40mg/ bottle) with a dose of 2mg/kg (maximum dose of 160mg), once daily, for three consecutive days. The initial study drug will be administered as soon as possible after randomization. It is recommended that the initial study drug administrated before arterial access closure, but it should not be delayed more than 2 hours after arterial access closure.
Sponsors
YiLin
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years. * The time from last known well to randomization was within 24 hours. * Anterior circulation ischemic stroke was preliminarily determined according to clinical symptoms or imaging examination. * Occlusion of the intracranial internal carotid artery, the M1- or M2-segment of the middle cerebral artery by confirmed by CT angiography (CTA), MR angiography (MRA), or digital subtraction angiography (DSA). * Baseline National Institutes of Health Stroke Scale (NIHSS) ≥ 6. * Baseline Alberta Stroke Program Early CT Score (ASPECTS) \< 6 (based on non-contrast CT or MRI) or core infarct volume ≥ 50 ml (based on CTP with rCBF \< 30%). * Planned treatment with endovascular thrombectomy (EVT). * Baseline peripheral blood lymphocyte \< 0.8×10#/L * Informed consent obtained from patients or their legal representatives.
Exclusion criteria
* Intracranial hemorrhage confirmed by cranial CT or MRI. * mRS score \> 2 before the time of last known well. * Pregnant or lactating women. * Allergic to contrast agents or glucocorticoids. * Participating in other clinical trials. * The artery is tortuous so that the thrombectomy device cannot reach the target vessel. * Bleeding history (gastrointestinal and urinary tract bleeding) in recent 1 month. * Chronic hemodialysis and severe renal insufficiency (glomerular filtration rate \< 30 ml/min or serum creatinine \> 220 umol/L \[2.5 mg/ dL\]). * Life expectancy due to any advanced disease \< 6 months. * Follow-up is not expected to be completed. * Intracranial aneurysm and arteriovenous malformation. * Brain tumors with imaging mass effect. * Systemic infectious disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| All-cause mortality at 90 (±7) days | From randomization to 90 (±7) days | Primary Efficacy Outcome. Defined as the number of any cause deaths observed divided by the number of subjects observed over the 90-day study period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relative hemispheric volume at 48 hours | From randomization to 48 hours | Secondary Efficacy Outcome |
| Proportion of patients with pneumonia | From randomization until the date of discharge, an average of 1 week | Secondary Safety Outcome |
| Proportion of patients with gastrointestinal haemorrhage within 7 days after EVT | From randomization to 7 days | Secondary Safety Outcome |
| Incidence of any complications | From date of randomization until the date of discharge, an average of 1 week | Secondary Safety Outcome |
| Incidence of any (serious) adverse events | From randomization to 90 (±7) days | Secondary Safety Outcome |
| Time from randomization to the occurrence of death from any cause at 90 (±7) days | From randomization to 90 (±7) days | Secondary Efficacy Outcome; To evaluate death rate of the two treatment groups |
| mRS ordinal shift at 90 (±7) days (scores 5 and 6 are merged) | From randomization to 90 (±7) days | Secondary Efficacy Outcome |
| Proportion of patients with mRS score 0 to 4 at 90 (±7) days | From randomization to 90 (±7) days | Secondary Efficacy Outcome |
| Proportion of patients with mRS score 0 to 3 at 90 (±7) days | From randomization to 90 (±7) days | Secondary Efficacy Outcome |
| Proportion of patients with mRS score 0 to 2 at 90 (±7) days | From randomization to 90 (±7) days | Secondary Efficacy Outcome |
| Proportion of patients with mRS score 0 to 1 at 90 (±7) days or return to pre-stroke mRS score (for patients with prestroke mRS > 1) | From randomization to 90 (±7) days | Secondary Efficacy Outcome |
| Midline shift at 48 hours | From randomization to 48 hours | Secondary Efficacy Outcome |
| Proportion of patients with midline shift maximum > 5 mm within 48 hours (%) | From randomization to 48 hours | Secondary Efficacy Outcome |
| Net water uptake at 48 hours | From randomization to 48 hours | Secondary Efficacy Outcome |
| Proportion of patients with decompressive craniectomy after EVT | From randomization until the date of discharge, an average of 1 week | Secondary Efficacy Outcome |
| NIHSS score at 5-7 days or at early discharge | From randomization to 5-7 days (or at early discharge) | Secondary Efficacy Outcome |
| EQ-5D-5L VAS at 90 (±7) days | From randomization to 90 (±7) days | Secondary Efficacy Outcome |
| Proportion of patients with symptomatic intracranial haemorrhage (SICH) within 48 hours after EVT | From randomization to 48 hours | Primary Safety Outcome. Based on the modified Heidelberg Bleeding Classification. |
| Proportion of patients with any intracranial haemorrhage (ICH) within 48 hours after EVT | From randomization to 48 hours | Secondary Safety Outcome. Based on the modified Heidelberg Bleeding Classification. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients with mRS score 0 to 1 at 1 year or return to pre-stroke mRS score (for patients with pre-stroke mRS > 1) | From randomization to 1 year | Tertiary Efficacy Outcome |
| EQ-5D-5L VAS at 1 year | From randomization to 1 year | Tertiary Efficacy Outcome |
| mRS ordinal shift at 1 year (scores 5 and 6 are merged) | From randomization to 1 year | Tertiary Efficacy Outcome |
| Proportion of patients with mRS score 0 to 2 at 1 year | From randomization to 1 year | Tertiary Efficacy Outcome |
Countries
China
Contacts
Primary ContactYi Lin, MD
Backup ContactYing Fu, MD
Outcome results
None listed