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

Phase 3

Completed

• Conditions: Mechanical Thrombectomy; Edaravone Dexborneol; Acute Ischemic Stroke; Phase III
• Interventions: Drug: Edaravone Dexborneol Concentrated Solution for injection; Drug: Edaravone Dexborneol placebo

• Registration Number: NCT05249920
• Lead Sponsor: Beijing Tiantan Hospital

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2022-01-25
• Study First Submitted QC: 2022-02-21
• Study First Posted: 2022-02-22
• Study Start: 2022-03-18
• Primary Completion: 2023-02-17
• Study Completion: 2023-05-19
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-20
• Last Update Posted: 2023-08-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1362

Inclusion Criteria

1. 18 - 80 years, male or female;

2. 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;

3. Within 24 hours of stroke onset;

4. 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);

5. Planned to receive bridging therapy (endovascular therapy after intravenous alteplase) or direct endovascular therapy;

6. Pre-morbid modified Rankin Scale ≤1;

7. 6 ≤ NIHSS ≤ 25 before endovascular therapy;

8. Signed informed consent from subjects or legally authorized representatives

Exclusion Criteria

1. CT indicates intracranial hemorrhagic diseases, such as hemorrhagic stroke, subdural hematoma, ventricular hemorrhage, or subarachnoid hemorrhage, etc.;
2. Had been given any intravenous thrombolytic drug other than alteplase before bridging therapy;
3. Hypersensitive to edaravone, (+)-2- dexborneol or auxiliary materials;
4. Prior receipt of edaravone or any other neuroprotective drugs;
5. History of congenital or acquired hemorrhagic disease, coagulation factor deficiency disease, or thrombocytopenic disease, etc.;
6. Systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg after antihypertensive treatment;
7. Serum alanine aminotransferase (ALT) or aspartate transaminase (AST) elevates over 3 times of upper limit of normal;
8. 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;
9. Pregnancy, lactation, or planned pregnancy within 90 days;
10. Those who cannot complete informed consent or follow-up treatment due to severe mental disorder or dementia;
11. Those with a malignant tumor, severe systemic diseases, or predict survival time <90 days;
12. Participate in another interventional clinical study within 30 days before randomization or participate in another interventional clinical study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Edaravone Dexborneol group	Edaravone Dexborneol Concentrated Solution for injection	Patients in this arm will be given Edaravone Dexborneol Concentrated Solution for injection twice a day for 10 to 14 days.
Edaravone Dexborneol Placebo group	Edaravone Dexborneol placebo	Patients in this arm will be given a placebo of Edaravone Dexborneol for injection twice a day for 10 to 14 days.

Primary Outcome Measures

Name	Time	Method
Favorable functional outcome	at 90 days after randomization	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
Incidence of severe adverse event (Safety outcome)	at 90 days after randomization	The incidence of Severe Adverse Event (SAE) emerged during the whole study period

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Beijing Tiantan Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China