Clinical trial NCT06238024: Effect of Interleukin-6 Receptor Inhibition in Patients With Ischemic Stroke Undergoing Endovascular Treatment
Official title: Effect of Interleukin-6 Receptor Inhibition in Patients With Ischemic Stroke Undergoing Endovascular Treatment: a Double-blind, Randomized, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Interleukin-6
Ischemic Stroke
Endovascular Treatment
Keywords: Acute ischemic stroke
Tocilizumab
Neuroprotection
Outcome
Lead sponsor: Suzhou Municipal Hospital of Anhui Province
Sponsor class: OTHER
Collaborators: name: Xuanwu Hospital, Beijing
First posted: 2024-02-02
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Change from baseline in infarct-core volume
timeFrame: 72 hours
Secondary outcomes:
measure: Early neurological improvement
timeFrame: within 24 hours
measure: NIHSS score
timeFrame: 24 hours
measure: Proportion of successful reperfusion (mTICI 2b/3)
timeFrame: immediate postoperative
measure: Proportion of recanalization on follow-up CTA or MRA
timeFrame: 72 hours
measure: Incidence of cerebral hemorrhage
timeFrame: 72 hours
measure: Incidence of symptomatic cerebral hemorrhage
timeFrame: 72 hours
measure: NIHSS score
timeFrame: 7 days
measure: Incidence of stroke-associated pneumonia
timeFrame: 7 days
measure: Incidence of decompressive craniectomy
timeFrame: 7 days
measure: Proportion of patients with functional independence (mRS 0-2)
timeFrame: 90 days
measure: Shift analysis of mRS score
timeFrame: 90 days
measure: Barthel Index
timeFrame: 90 days
measure: EuroQoL Group 5-Dimension Self-Report Questionnaire (EQ-5D)
timeFrame: 90 days
measure: Death
timeFrame: 90 days
measure: Adverse events and serious adverse events
timeFrame: 90 days
Other outcomes:
measure: Change of hsCRP levels from admission to 72 hours
timeFrame: 72 hours
measure: Change of inflammatory blood biomarkers
timeFrame: baseline, 24 hours, 48 hours, and 72 hours
Locations:
city: Suzhou
country: China
facility: Suzhou Municipal Hospital of Anhui Province
state: Anhui
Study officials:
affiliation: Xuanwu Hospital, Beijing
name: Chuanjie Wu, M.D.
role: STUDY_DIRECTOR
affiliation: Suzhou Municipal Hospital of Anhui Province
name: Zhengfei Ma, M.M.
role: STUDY_DIRECTOR
affiliation: Xuanwu Hospital, Beijing
name: Xunming Ji, M.D.
role: STUDY_CHAIR
affiliation: Xuanwu Hospital, Beijing
name: Xuehong Chu, M.D.
role: PRINCIPAL_INVESTIGATOR
References: