Endovascular Treatment, Interleukin-6, Ischemic Stroke
Conditions
Keywords
Acute ischemic stroke, Tocilizumab, Neuroprotection, Outcome
Brief summary
Tocilizumab may exert neuroprotective effects in patients with ischemic stroke undergoing endovascular treatment
Detailed description
Vascular recanalization techniques, including thrombolysis and thrombectomy, have become the mainstay of treatment for acute ischemic stroke. However, some patients still experience poor prognosis, with ineffective recanalization and reperfusion brain injury being the major contributors to unfavorable outcomes. Studies have indicated that tocilizumab, used in ST-segment elevation and non-ST-segment elevation myocardial infarction, exhibits anti-inflammatory and myocardial protective effects. Nevertheless, whether tocilizumab can provide neuroprotection in the early stages of acute large vessel recanalization remains uncertain. Given the above evidence, the aim of this study was to investigate whether combination therapy with tocilizumab in the early phase of recanalization of acute large vessel occlusion could further exert a beneficial effect and thus improve the poor prognosis of patients.
Interventions
DRUGTocilizumab
Single dose intravenous application
DRUGNaCl 0.9% 100ml
Single dose intravenous application
Sponsors
Xuanwu Hospital, Beijing
Suzhou Municipal Hospital of Anhui Province
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 80 Years
Healthy volunteers
No
Inclusion criteria
* Inclusion criteria: 1. Age 18-80 years. 2. Acute ischemic stroke caused by occlusion of intracranial segment of the internal carotid artery, middle cerebral artery M1, or M2 segment. 3. NIHSS ≥ 6. 4. Meeting the criteria of endovascular treatment: ① ASPECTS score ≥ 6, possibile to start endovascular treatment within 6 hours from stroke onset. ② Stroke onset between 6-16 hours, meeting DEFUSE-3 criteria (infarct core volume \< 70ml, mismatch ratio ≥ 1.8, and mismatch volume \> 15ml), or DAWN criteria (NIHSS ≥ 10 and infarct core volume \< 31ml; or NIHSS ≥ 20 and infarct volume 31-51ml). ③ Stroke onset between 16-24 hours, meeting DAWN criteria (NIHSS ≥ 10 and infarct core volume \< 31ml; or NIHSS ≥ 20 and infarct volume 31-51ml). ④ When ASPECTS score is \< 6, meeting RESCUE-Japan LIMIT criteria (ASPECTS score 3-5; stroke onset within 6 hours or between 6-24 hours but no acute stroke signs on FLAIR), or ANGEL-ASPECT criteria (stroke onset within 24 hours, ASPECTS 3-5; or onset within 24 hours, ASPECTS 0-2 and infarct core volume 70-100 mL; or onset between 6-24 hours, ASPECTS \> 5 and infarct core volume 70-100 mL), or SELECT2 criteria (ASPECTS 3-5; or infarct core volume greater than 50ml). 5. Experimental drug administration had to be possible within 24 hours after stroke onset. 6. Obtained Informed consent from the patient or their legal representative. *
Exclusion criteria
1. Hemorrhagic diseases visible on head CT: hemorrhagic stroke, epidural hematoma, subdural hematoma, intraventricular hemorrhage, subarachnoid hemorrhage, etc. 2. Pre-stroke mRS score \> 1. 3. Known allergy to tocilizumab or excipients. 4. Known allergy to iodinated contrast agents. 5. Anticipated difficulty in completing endovascular treatment due to vascular tortuosity. 6. History of congenital or acquired bleeding disorders, coagulation factor deficiency diseases, thrombocytopenic diseases, etc. 7. Systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg despite blood pressure control. 8. Neutrophil \< 2×10 9/L. 9. Platelet \< 100×10 9/L. 10. Blood glucose \< 2.8 mmol/L (50 mg/dl) or \> 22.2 mmol/L (400 mg/dl). 11. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 1.5 times the upper limit of normal. 12. Known recent or current serum creatinine exceeding 1.5 times the upper limit of normal or estimated glomerular filtration rate (eGFR) \< 60 mL/min. 13. Pregnant, lactating, or planning pregnancy within 90 days. 14. Severe mental disorders or inability to comply with informed consent and follow-up requirements due to dementia. 15. Concurrent malignant tumors or severe systemic diseases with an expected survival of less than 90 days. 16. Presence of autoimmune diseases or use of immunosuppressive drugs. 17. Systemic infectious diseases 18. Participation in another interventional clinical study within 30 days before randomization or currently participating in another interventional clinical study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in infarct-core volume | 72 hours | The infarct-core volume is determined by diffusion-weighted MRI, CT, or CTP images. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Early neurological improvement | within 24 hours | Decrease in National Institute of Health stroke scale (NIHSS) score of ≥8 or NIHSS score of 0-2 within 24 hours. NIHSS scores range from 0 to 42, with higher scores indicating greater neurologic deficit |
| NIHSS score | 24 hours | National Institutes of Health Stroke Scale (NIHSS) scores range from 0 to 42, with higher scores indicating greater neurologic deficit |
| Proportion of successful reperfusion (mTICI 2b/3) | immediate postoperative | mTICI denotes modified Treatment in Cerebral Ischemia classification, with scores ranging from 0 (no flow) to 3 (normal flow) |
| Proportion of recanalization on follow-up CTA or MRA | 72 hours | — |
| Incidence of cerebral hemorrhage | 72 hours | — |
| Incidence of symptomatic cerebral hemorrhage | 72 hours | — |
| Incidence of stroke-associated pneumonia | 7 days | — |
| Death | 90 days | — |
| Adverse events and serious adverse events | 90 days | — |
| Incidence of decompressive craniectomy | 7 days | — |
| Proportion of patients with functional independence (mRS 0-2) | 90 days | Scores on the modified Rankin scale range from 0 to 6, with higher scores indicating greater disability |
| Shift analysis of mRS score | 90 days | Scores on the modified Rankin scale range from 0 to 6, with higher scores indicating greater disability |
| Barthel Index | 90 days | The Barthel index is an ordinal scale for measuring performance of activities of daily living. Scores ranges from 0 to 20, with 0 indicating severe disability and 19 or 20 indicating no disability that interferes with daily activities. |
| EuroQoL Group 5-Dimension Self-Report Questionnaire (EQ-5D) | 90 days | EQ-5D is a standardized instrument for the measurement of health status. Scores range from -0.33 to 1.00, with higher scores indicating a better quality of life |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change of hsCRP levels from admission to 72 hours | 72 hours | — |
| Change of inflammatory blood biomarkers | baseline, 24 hours, 48 hours, and 72 hours | Interleukin-6 |
Countries
China
Outcome results
None listed