Effect of Interleukin-6 Receptor Inhibition in Patients With Ischemic Stroke Undergoing Endovascular Treatment (IRIS)

Suzhou Municipal Hospital of Anhui Province

Status and phase: Completed; Phase 3; Phase 2

Conditions: Ischemic Stroke; Endovascular Treatment; Interleukin-6

Treatments: Drug: Tocilizumab; Drug: NaCl 0.9% 100ml

Study type: Interventional

Funder types: Other

Identifiers

NCT06238024

SZSLYY

Details and patient eligibility

About

Tocilizumab may exert neuroprotective effects in patients with ischemic stroke undergoing endovascular treatment

Full 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.

Enrollment: 108 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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108 participants in 2 patient groups, including a placebo group

Tocilizumab group

Experimental group

Description:

Intravenously for more than 1 hour.

Treatment:

Drug: Tocilizumab

Control group

Placebo Comparator group

Description:

Intravenously for more than 1 hour.

Treatment:

Drug: NaCl 0.9% 100ml