IRIS-sICAS is a multicenter, randomized, double-blind, placebo-controlled clinical trialis a multicenter, randomized, double-blind, placebo-controlled clinical trial, to assess the safety and efficacy of tocilizumab injection in lowering the incidence of newly diagnosis ischemic stroke and improving prognosis in symptomatic intracranial atherosclerosis patients.
Intracranial atherosclerosis (ICAS) is one of the most common causes of stroke worldwide, and the currently recommended intensive pharmacologic and surgical treatments show only modest efficacy, with approximately 20% of strokes still recurring, for which there is no targeted treatment. Tocilizumab is a recombinant humanized anti-human interleukin-6 receptor monoclonal antibody that exerts anti-inflammatory effects by specifically binding to the IL-6 receptor and blocking IL-6 signal transduction. Previous studies have shown that tocilizumab can effectively attenuate acute ischemic injury in the early stage of myocardial infarction and has potentially anti-atherosclerotic effects. However, application in ICAS not yet reported. This study is a multicenter, randomized, double-blind, placebo-controlled clinical trial, which enrolled patients with symptomatic ICAS occurring within 72 hours of ischemic stroke or high-risk transient ischemic attack. Patients who consented to participate in the study were randomly assigned in a 1:1 ratio to receive a single infusion of 320mg tocilizumab or placebo (saline injection), and patients were followed up to assess the safety and efficacy of tocilizumab injection in lowering the incidence of newly diagnosis ischemic stroke and improving prognosis.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
486
Single dose intravenous application
Single dose intravenous application
The proportion of patients with newly diagnosed ischemic stroke within 90(±7) days
Stroke is defined as an acute episode of focal neurological dysfunction associated with cerebral vascular injury, with no apparent non-vascular cause such as brain infection, trauma, tumor, seizure, severe metabolic disease, or degenerative neurological disease. Ischemic stroke is defined as an acute episode of a new focal neurological deficit lasting \>24 hours, an increase in existing focal neurological deficit lasting \>24 hours, or a focal neurological deficit lasting \<24 hours that is associated with evidence of new ischemic changes based on neuroimaging. The focal neurological deficit is not attributable to a non-ischemic etiology. Hemorrhage may be a consequence of ischemic stroke, and in this situation, the stroke is an ischemic stroke with hemorrhagic transformation but not a hemorrhagic stroke.
Time frame: 90(±7) days
The functional neurological status at 6(±1) days or discharge if earlier from baseline
The functional neurological status is evaluated through National Institute of Health Stroke Scale(NIHSS). The NIHSS is a standardized neurological examination score that is a valid and reliable measure of disability and recovery after acute stroke. Scores range from 0 to 42, with higher scores indicating more severe disability. The scale includes measures of level of consciousness, extra ocular movements, motor and sensory tests, coordination, language and speech evaluations.
Time frame: 6(±1) days
The incidence of composite events including any type of stroke (ischemic stroke(IS), subarachnoid hemorrhage(SAH), or intracerebral hemorrhage(ICH)), myocardial infarction(MI), and transient ischemic attack(TIA) and each of foresaid events at 30(±3) days
IS is defined as an acute episode of a new focal neurological deficit lasting \>24 hrs, an increase in existing focal neurological deficit lasting \>24 hrs, or a focal neurological deficit lasting \<24 hrs that is associated with evidence of new ischemic changes based on neuroimaging. The focal neurological deficit is unrelated to a non-ischemic etiology. Hemorrhage may be a result of IS. Hemorrhagic stroke including SAH and ICH is defined as a new focal neurological deficit caused by a nontraumatic intraparenchymal hemorrhage, with neuroimaging evidence of corresponding intraparenchymal hemorrhage, except hemorrhagic transformation of an IS. MI is defined as an episode of myocardial necrosis in a clinical setting consistent with myocardial ischemia. TIA is defined as a transient episode of a focal ischemic neurological deficit resolving completely within 24 hrs, caused by focal cerebral or retinal ischemia, without evidence of corresponding cerebral infarction based on neuroimaging.
Time frame: 30(±3) days
The incidence of composite events including any type of stroke (ischemic stroke(IS), subarachnoid hemorrhage(SAH), or intracerebral hemorrhage(ICH)), myocardial infarction(MI), and transient ischemic attack(TIA) and each of foresaid events at 90(±7) days
IS is defined as an acute episode of a new focal neurological deficit lasting \>24 hrs, an increase in existing focal neurological deficit lasting \>24 hrs, or a focal neurological deficit lasting \<24 hrs that is associated with evidence of new ischemic changes based on neuroimaging. The focal neurological deficit is unrelated to a non-ischemic etiology. Hemorrhage may be a result of IS. Hemorrhagic stroke including SAH and ICH is defined as a new focal neurological deficit caused by a nontraumatic intraparenchymal hemorrhage, with neuroimaging evidence of corresponding intraparenchymal hemorrhage, except hemorrhagic transformation of an IS. MI is defined as an episode of myocardial necrosis in a clinical setting consistent with myocardial ischemia. TIA is defined as a transient episode of a focal ischemic neurological deficit resolving completely within 24 hrs, caused by focal cerebral or retinal ischemia, without evidence of corresponding cerebral infarction based on neuroimaging.
Time frame: 90(±7) days
Proportion of patients with functional independence at 90(±7) days
Functional independence is defined as the modified Rankin Scale(mRS) score ranging from 0-2. The mRS is a valid and reliable clinician-reported measure of global disability that has been widely applied for evaluating recovery from stroke. It is a scale used to measure functional recovery (the degree of disability or dependence in daily activities) of people who have suffered a stroke. mRS scores range from 0 to 6, with 0 indicating no residual symptoms; 5 indicating bedbound, requiring constant care; and 6 indicating death.
Time frame: 90(±7) days
Health-related quality of life at 90(±7) days
Health-related quality of life is assessed with the European Quality Five Dimensions Five Level scale (EQ-5D-5L). The EQ-5D-5L is a generic instrument for describing and valuing health. It is based on a descriptive system that defines health in terms of five dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has five response categories corresponding to: no problems, slight, moderate, severe and extreme problems. The instrument is designed for self-completion, and respondents also rate their overall health on the day of the interview on a 0-100 hash-marked, vertical visual analogue scale.
Time frame: 90(±7) days
Mortality at 90(±7) days
Mortality rates are defined as the number of deaths observed divided by the number of subjects observed over the 90-day study period.
Time frame: 90(±7) days
Incidence of serious adverse events
Including but not limited to acute respiratory failure, severe or malignant cerebral artery infarction, acute heart failure, debridement decompression, and other major medical events that can result in death, immediately life-threatening, hospitalization or prolongation of this hospitalization, terminally or severely disabling/incapacitating, the loss of a significant ability to maintain normal life functioning, or medical intervention to avoid the above outcomes.
Time frame: 90(±7) days
Change of inflammatory blood biomarkers from admission to 72 hours
Interleukin-6 (IL-6)
Time frame: 72 hours
Change of inflammatory blood biomarkers from admission to 72 hours
hypersensitive C-reactive protein (hsCRP)
Time frame: 72 hours
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