Treatment of Acute Ischemic STroke With Edaravone Dexborneol II (TASTE-2)

Study Overview
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Brief Summary
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This study is a multicentre, randomized, double-blind, placebo parallel controlled, investigator-sponsored study that aims to investigate the efficacy and safety of Edaravone Dexborneol treatment in patients with acute ischemic stroke who had received early reperfusion therapy.

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 Edaravone Dexborneol treatment in patients with acute ischemic stroke who had received early reperfusion therapy. Patients who were eligible to the inclusion criteria and ineligible to the exclusion criteria will be randomly assigned into two groups by a 1:1 ratio after the ICF was received. Patients in one arm will be given 15 ml edaravone and dexborneol concentrated solution for injection (37.5 mg, containing edaravone 30 mg and dexborneol 7.5 mg) 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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Treatment of Acute Ischemic STroke With Edaravone Dexborneol Ⅱ (TASTE-2)

Conditions
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Acute Ischemic Stroke, Mechanical Thrombectomy, Edaravone Dexborneol, Phase III

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: 18 - 80 years, male or female; Clinically diagnosed as acute anterior ischemic stroke, artery occlusion occurred at the terminal of the intracranial carotid artery, T-shaped bifurcation or M1 segment of the middle cerebral artery; Within 24 hours of stroke onset; Eligible for other imaging indications for bridging therapy or direct mechanical thrombectomy: ASPECTS ≥6 certified by the latest brain CT imaging; Patients within 6-16 hours after stroke onset should meet the mismatch criteria, which was defined as infarction core volume <70 ml, mismatch ratio ≥1.8 and the ischemic volume > 15 ml (DEFUSE-3 Criteria); or NIHSS score ≥ 10 with infarction -core volume < 31 cm3, or NIHSS score ≥ 20 with infarction core volume ≤ 51 cm3 (DAWN Criteria); Patients within 16-24 hours after stroke onset should meet the mismatch criteria, which was defined as NIHSS score ≥ 10 with infarction-core volume < 31 cm3, or NIHSS score ≥ 20 with infarction-core volume ≤ 51 cm3 (DAWN Criteria); Planned to receive bridging therapy (endovascular therapy after intravenous alteplase) or direct endovascular therapy; Pre-morbid modified Rankin Scale ≤1; 6 ≤ NIHSS ≤ 25 before endovascular therapy; Signed informed consent from subjects or legally authorized representatives Exclusion Criteria: CT indicates intracranial hemorrhagic diseases, such as hemorrhagic stroke, subdural hematoma, ventricular hemorrhage, or subarachnoid hemorrhage, etc.; Had been given any intravenous thrombolytic drug other than alteplase before bridging therapy; 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.; Systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg after antihypertensive treatment; Serum alanine aminotransferase (ALT) or aspartate transaminase (AST) elevates over 3 times of upper limit of normal; Recent or current serum creatinine is known to exceed 1.5 times the upper limit of normal, or estimated glomerular filtration rate (eGFR) < 60 mL/min; 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.

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: 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 |
| --- | --- | --- |
| Favorable functional outcome | Rate of favorable functional outcome defined as a modified Rankin Scale (mRS, scores range from 0 to 6, with 0 to 2 indicating favorable outcome and 3 to 6 indicating unfavorable outcome including 6 as death) score of 0-2 | at 90 days after randomization | 
| Incidence of severe adverse event (Safety outcome) | The incidence of Severe Adverse Event (SAE) emerged during the whole study period | at 90 days after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Excellent functional outcome | Rate of excellent functional outcome defined as a mRS score 0-1 | at 90 days after randomization | 
| NIHSS score change | The change of NIHSS score defined as the NIHSS score of day 10-14 minus that of baseline | at 10-14 days after randomization | 
| NIHSS score decreases ≥4 | Defined as the proportion of patients with NIHSS score decrease ≥ 4 from day 10-14 to baseline | at 10-14 days after randomization | 
| All-cause mortality | All-cause mortality at 90 days after randomization | at 90 days after randomization | 
| Symptomatic intracranial hemorrhage (sICH) | The proportion of patients who experienced sICH | at 24-36 hours after randomization | 
| Neurological deterioration | Defined as the NIHSS score increases ≥4 from day 1 to baseline | at day 1 after randomization | 
| Stroke recurrence | Defined as a new ischemic or hemorrhagic stroke occurred within 90 days after randomization | within 90 days after randomization | 
| Adverse events (AE) | The proportion of patients who experienced AE | within 90 days after randomization |