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

Ischemic Stroke Clinical Trial

— IRIS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06238024
• Other study ID #: SZSLYY
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: February 2, 2024
• Est. completion date: September 30, 2025

Study information

• Verified date: February 2024
• Source: Suzhou Municipal Hospital of Anhui Province
• Contact: Zhengfei Ma, M.M.
• Phone: +8613866586362
• Email: Zhengfeima[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 108
• Est. completion date: September 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

• 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:

? ASPECTS score = 6, possibile to start endovascular treatment within 6 hours from stroke onset.

? 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).

? Stroke onset between 16-24 hours, meeting DAWN criteria (NIHSS = 10 and infarct core volume < 31ml; or NIHSS = 20 and infarct volume 31-51ml).

? 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.

Related Conditions & MeSH terms

• Cerebral Infarction
• Endovascular Treatment
• Interleukin-6
• Ischemia
• Ischemic Stroke
• Stroke

Intervention

Drug:
• Tocilizumab
Single dose intravenous application
• NaCl 0.9% 100ml
Single dose intravenous application

Locations

Country	Name	City	State
China	Suzhou Municipal Hospital of Anhui Province	Suzhou	Anhui

Sponsors (2)

Lead Sponsor	Collaborator
Suzhou Municipal Hospital of Anhui Province	Xuanwu Hospital, Beijing

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change of hsCRP levels from admission to 72 hours		72 hours
Other	Change of inflammatory blood biomarkers	Interleukin-6	baseline, 24 hours, 48 hours, and 72 hours
Primary	Change from baseline in infarct-core volume	The infarct-core volume is determined by diffusion-weighted MRI, CT, or CTP images.	72 hours
Secondary	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
Secondary	NIHSS score	National Institutes of Health Stroke Scale (NIHSS) scores range from 0 to 42, with higher scores indicating greater neurologic deficit	24 hours
Secondary	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
Secondary	Proportion of recanalization on follow-up CTA or MRA		72 hours
Secondary	Incidence of cerebral hemorrhage		72 hours
Secondary	Incidence of symptomatic cerebral hemorrhage		72 hours
Secondary	NIHSS score	National Institutes of Health Stroke Scale (NIHSS) scores range from 0 to 42, with higher scores indicating greater neurologic deficit	7 days
Secondary	Incidence of stroke-associated pneumonia		7 days
Secondary	Incidence of decompressive craniectomy		7 days
Secondary	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
Secondary	Shift analysis of mRS score	Scores on the modified Rankin scale range from 0 to 6, with higher scores indicating greater disability	90 days
Secondary	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
Secondary	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
Secondary	Death		90 days
Secondary	Adverse events and serious adverse events		90 days