Effect of Early Versus Late Initiation of Edaravone Dexborneol on Neural Function in Patients With Acute Ischemic Stroke

Study Overview
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Brief Summary
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The primary objective of this study was to evaluate the efficacy and safety of initiation of edaravone dextivel therapy compared with placebo in patients with acute ischaemic stroke (early and late) and to explore the optimal time window for brain cell protective therapy of edaravone dexborneol.

Detailed Description
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This is a multicentre, randomized, double-blind, placebo-controlled trial that aims to investigate the efficacy and safety of (early and late) initiation treatment of Edaravone Dexborneol versus placebo in patients with acute ischemic stroke, and to explore the optimal time window for brain cell protective therapy of Edaravone Dexborneol. Patients who were eligible to the inclusion criteria and ineligible to the exclusion criteria will be stratified by time to trial drug: early (<3 hours) and late (3-6 hours). Then each layer will be randomly assigned into two groups by a 1:1 ratio after the ICF was received. Patients in one arm will be given 15ml edaravone and dexborneol concentrated solution for injection (37.5mg, containing edaravone 30mg and dexborneol 7.5mg) twice a day for 10-14 days, and those in the other arm will be given an equivalent placebo drug. All patients will be followed up for 90 days. The primary outcome is the proportion of modified Rankin Scale 0-2 and the safety outcome is the proportion of severe adverse events.

Official Title
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Effect of Early Versus Late Initiation of Edaravone Dexborneol on Neural Function in Patients With Acute Ischemic Stroke-A Multicenter, Randomized, Double-blind, Placebo-controlled, Trial

Conditions
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Ischemic Stroke, Acute, Treatment Outcome

Intervention / Treatment
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* Drug: Edaravone Dexborneol Concentrated Solution for injection
* Drug: Edaravone Dexborneol placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-80 years old, gender is not limited; Clinically confirmed acute ischemic stroke; Within 6 hours of the onset of this stroke; NIHSS score of 4-24 at enrollment; mRS score before onset≤ 1 point; Subject and subject's agent are able and willing to sign informed consent. Exclusion Criteria: CT indicates intracranial hemorrhagic diseases, such as hemorrhagic stroke, subdural hematoma, ventricular hemorrhage, or subarachnoid hemorrhage, etc.; Previously known severe liver or kidney insufficiency (ALT or AST is greater than 3.0×ULN; serum Creatinine (SCr) is greater than 1.5×ULN, Creatinine Clearance (CrCl) is less than 50 ml/min or dialysis; Systolic blood pressure≥220 mmHg or <90mmHg； Recent stroke within prior 1 month； Hypersensitive to edaravone, (+)-2- dexborneol or auxiliary materials; Prior receipt of edaravone or any other neuroprotective drugs; History of congenital or acquired hemorrhagic disease, coagulation factor deficiency disease, or thrombocytopenic disease, etc.; Pregnancy, lactation, or planned pregnancy within 90 days; Those who cannot complete informed consent or follow-up treatment due to severe mental disorder or dementia; Those with a malignant tumor, severe systemic diseases, or predict survival time <90 days; Participate in another interventional clinical study within 30 days before randomization or participate in another interventional clinical study; The investigators consider the patients are not suitable for this trial.

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
Interventional Model Description: Subjects with AIS who met the criteria for inclusion were stratified 1:1 from onset to use of the investigational drug: early (< 3 hours) and late (3-6 hours). Each layer was then randomly assigned to two groups in a 1:1 ratio: the right group and the placebo group. Test group: Edaravone dextronicol concentrated solution for injection, 15ml / time (37.5mg / time, of which edaravone 30mg, (+)-2-camphol 7.5mg), that is, 3 bottles / time, 2 times a day, for 12±2 days; Control group: Equal dose of placebo, 15 ml / time, that is, 3 sticks / time, 2 times a day for 12±2 days.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Edaravone Dexborneol group<br>Patients in this arm will be given Edaravone Dexborneol Concentrated Solution for injection twice a day for 10 to 14 days. | Drug: Edaravone Dexborneol Concentrated Solution for injection<br>* Edaravone and Dexborneol Concentrated Solution for Injection, 15 ml (37.5 mg, containing edaravone 30 mg and dexborneol 7.5 mg) in 3 ampoule bottles, twice a day for 10 to 14 days.<br>* Other names: Xian Bi Xin,CFDA Approval Number H20200007;|
| Placebo Comparator: Edaravone Dexborneol Placebo group<br>Patients in this arm will be given a placebo of Edaravone Dexborneol for injection twice a day for 10 to 14 days | Drug: Edaravone Dexborneol placebo<br>* Edaravone and Dexborneol placebo, 15 ml in 3 ampoule bottles, twice a day for 10 to 14 days.<br>* Other names: Xian Bi Xin placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A 90-day mRS score of 0 to 2 in participants with acute ischaemic stroke | To assess the proportion of participants (early and late) who started edaravone dextrol compared with placebo with a 90-day mRS score of 0 to 2 in participants with acute ischaemic stroke | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurological recovery | The difference value of the NIHSS between Day 14/Day 90 and the baseline. | 90 days | 
| Modified Rankin scale | used to evaluate the functional outcomes after AIS，good prognosis (mRS score 0-2), generally good prognosis (mRS score 3-4) , Poor prognosis (mRS >4 points). | 90 days | 
| Quality of life score (EQ-5D) | Generic health status evaluated by EQ-5D questionnaire at the end of the therapy. | 90 days | 
| The incidence of serious adverse events | The percentage of the Severity Adverse Events within the 14 days/90 days of the therapy. | 90 days | 
| All-cause mortality | All-cause mortality at 90 days after randomization | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute ischemic stroke, Semi-dark band, Brain cell protection, Time window, Erafurone dextrol injection, Treatment Outcome