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

Effect of Interleukin-6 Receptor Inhibition in Patients With Ischemic Stroke Undergoing Endovascular Treatment: a Double-blind, Randomized, Placebo-controlled Trial

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

Study Overview

• Status: Recruiting
• Conditions: Ischemic Stroke; Endovascular Treatment; Interleukin-6
• Intervention / Treatment: Drug: Tocilizumab; Drug: NaCl 0.9% 100ml

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.

• Study Type: Interventional
• Enrollment (Estimated): 108
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Zhengfei Ma, M.M.; Phone Number: +8613866586362; Email: Zhengfeima@126.com
• Study Contact Backup: Name: Anzhi Li, M.M.; Phone Number: +8615903860581; Email: 365819805@qq.com

Study Locations

• China
  • Anhui
    • Suzhou, Anhui, China
      • Recruiting
      • Suzhou Municipal Hospital of Anhui Province
      • Contact: Zhengfei Ma, M.M.; Phone Number: 13866586362; Email: zhengfeima@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tocilizumab group; Intravenously for more than 1 hour.	Drug: Tocilizumab; Single dose intravenous application
Placebo Comparator: Control group; Intravenously for more than 1 hour.	Drug: NaCl 0.9% 100ml; Single dose intravenous application

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in infarct-core volume	The infarct-core volume is determined by diffusion-weighted MRI, CT, or CTP images.	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death		90 days
Early neurological improvement	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	within 24 hours
NIHSS score	National Institutes of Health Stroke Scale (NIHSS) scores range from 0 to 42, with higher scores indicating greater neurologic deficit	24 hours
Proportion of successful reperfusion (mTICI 2b/3)	mTICI denotes modified Treatment in Cerebral Ischemia classification, with scores ranging from 0 (no flow) to 3 (normal flow)	immediate postoperative
Proportion of recanalization on follow-up CTA or MRA		72 hours
Incidence of cerebral hemorrhage		72 hours
Incidence of symptomatic cerebral hemorrhage		72 hours
NIHSS score	National Institutes of Health Stroke Scale (NIHSS) scores range from 0 to 42, with higher scores indicating greater neurologic deficit	7 days
Incidence of stroke-associated pneumonia		7 days
Incidence of decompressive craniectomy		7 days
Proportion of patients with functional independence (mRS 0-2)	Scores on the modified Rankin scale range from 0 to 6, with higher scores indicating greater disability	90 days
Shift analysis of mRS score	Scores on the modified Rankin scale range from 0 to 6, with higher scores indicating greater disability	90 days
Barthel Index	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.	90 days
EuroQoL Group 5-Dimension Self-Report Questionnaire (EQ-5D)	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	90 days
Adverse events and serious adverse events		90 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of hsCRP levels from admission to 72 hours		72 hours
Change of inflammatory blood biomarkers	Interleukin-6	baseline, 24 hours, 48 hours, and 72 hours

Collaborators and Investigators

• Sponsor: Suzhou Municipal Hospital of Anhui Province
• Collaborators: Xuanwu Hospital, Beijing
• Investigators: Study Director: Chuanjie Wu, M.D., Xuanwu Hospital, Beijing; Study Director: Zhengfei Ma, M.M., Suzhou Municipal Hospital of Anhui Province; Study Chair: Xunming Ji, M.D., Xuanwu Hospital, Beijing; Principal Investigator: Xuehong Chu, M.D., Xuanwu Hospital, Beijing

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2024
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): September 30, 2025

Study Registration Dates

• First Submitted: January 15, 2024
• First Submitted That Met QC Criteria: January 24, 2024
• First Posted (Actual): February 2, 2024

Study Record Updates

• Last Update Posted (Estimated): February 6, 2024
• Last Update Submitted That Met QC Criteria: February 3, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Tocilizumab; Outcome; Neuroprotection; Acute ischemic stroke
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction
• Other Study ID Numbers: SZSLYY

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No