Xingnaojing for Mild-to-severe Acute Ischemic Stroke

Study Overview
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Brief Summary
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The main purpose of this trial is to determine whether Xingnaojing, intravenously administered within 24 hours of symptom onset, improves the daily living ability of acute ischemic stroke at 90 days.

Detailed Description
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The XMAS-2 study is a multicenter, randomized, double-blind, placebo-controlled clinical trial. The primary hypothesis of this trial is that Xingnaojing will improve the daily living ability of acute ischemic stroke at 90 days. Xingnaojing will be compared to placebo, combined with guidelines-based standard care in patients with acute ischemic stroke within 24 hours of symptom onset. All participants will have a National Institutes of Health Stroke Scale(NIHSS)entry score of 4-25. Participants who have planned or already received the intravenous thrombolysis or endovascular treatment will be excluded. The primary outcome will be determined at 90 days.

Official Title
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Xingnaojing for Mild-to-severe Acute Ischemic Stroke (XMAS-2): A Multicenter, Randomized, Double-blind, Placebo-Controlled Trial

Conditions
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Acute Ischemic Stroke, Stroke, Acute, Stroke, Ischemic

Intervention / Treatment
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* Drug: Xingnaojing injection
* Drug: Xingnaojing placebo injection
* Other: Standard care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Acute ischemic stroke； Symptom onset within 24 hours； Age ≥ 18 and ≤ 80 years； NIHSS score ≥ 4 and ≤ 25； Patient or legally authorized representative has signed informed consent. Exclusion Criteria: Planned or already receiving intravenous thrombolysis or endovascular treatment; Suspected secondary stroke caused by tumor, brain trauma, or hematological diseases; Already dependent in activities of daily living before the present acute stroke (defined as modified Rankin Scale score ≥ 2) ; Other conditions that cause cardiogenic embolism (e.g., atrial fibrillation, rheumatic heart disease, valvular heart disease); Other conditions that lead to motor dysfunction (e.g., severe osteoarthrosis, rheumatoid arthritis); Significant renal or hepatic insufficiency (defined as a serum creatinine concentration, alanine aminotransferase (ALT), or aspartate aminotransferase (AST) value that is twice the upper limit of normal); Life expectancy of 3 months or less due to other life-threatening illness (e.g.,advanced cancer) Other conditions that render outcomes or follow-up unlikely to be assessed; Known to be pregnant or breastfeeding; Currently receiving an investigational drug;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Xingnaojing<br>Subjects will receive intravenously administered Xingnaojing injection, combined with guidelines-based standard care. | Drug: Xingnaojing injection<br>* Xingnaojing injection (20 ml)+0.9% diluted sodium chloride injection 250ml, IV (in the vein), every 12 hours for 10 days.<br>Other: Standard care<br>* Guidelines-based standard care for acute ischemic stroke.<br>|
| Placebo Comparator: Placebo<br>Subjects will receive intravenously administered Xingnaojing placebo, combined with guidelines-based standard care. | Drug: Xingnaojing placebo injection<br>* Xingnaojing placebo injection (20 ml)+0.9% diluted sodium chloride injection 250ml, IV (in the vein), every 12 hours for 10 days.<br>Other: Standard care<br>* Guidelines-based standard care for acute ischemic stroke.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients independent. | Proportion of patients independent is defined as Modified Rankin Scale score of 0, 1, or 2.The Modified Rankin Scale Score ranges from 0 (best score) to 6 (worst score). | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early neurological deterioration. | The early neurologic deterioration is defined as an increase of 1 points or more in the National Institute of Health Stroke Scale (NIHSS) score between baseline and 3 days. The NIHSS score ranges from 0 (best score) to 42 (worst score). | Baseline and 3 days | 
| Neurological impairment evaluated by National Institute of Health Stroke Scale (NIHSS). | Comparison of the change in the NIHSS scores from baseline to 10 days in the two groups.The NIHSS score ranges from 0 (best score) to 42 (worst score). | Baseline and 10 days | 
| Patient reported outcome | Patient reported outcome (PRO) scale of stroke at 10 days.The PRO score ranges from 36(best score) to 180 (worst score). | 10 days | 
| State of consciousness | The state of consciousness evaluated by Glasgow Coma Scale at 7 days. The Glasgow score ranges from 3(worst score) to 15 (best score). | 48 hours and 7 days | 
| Activities of daily living | Activities of daily living will be measured by Barthel Index score at 30 days and 90 days.The Barthel Index score ranges from 0 (worst score) to 100 (best score). | 30 days and 90 days | 
| The proportion of patients independent at 30 days. | The proportion of patients independent will be evaluated by mRS at 30 days.The mRS score ranges from 0 (best score) to 6 (worst score). | 30 days | 
| The recurrence rate of cerebrovascular events | The recurrence rate of cerebrovascular events within 90 days. | Within 90 days | 
| Stroke related deaths and deaths from any cause | Stroke related deaths and deaths from any cause within 10 days and 90 days after symptom onset. | Within 10 days and 90 days | 
| Safety end points | Number of patients with any adverse events, results of electrocardiography, vital signs and laboratory tests (complete blood count, chemistry and urinalysis). | 10 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute ischemic stroke, Xingnaojing injection, Traditional Chinese Medicine, Double-Blind, Randomized Controlled Trial