Clinical trial NCT05249920: Treatment of Acute Ischemic STroke With Edaravone Dexborneol II (TASTE-2)
Official title: Treatment of Acute Ischemic STroke With Edaravone Dexborneol Ⅱ (TASTE-2)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Ischemic Stroke
Mechanical Thrombectomy
Edaravone Dexborneol
Phase III
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
First posted: 2022-02-22
Enrollment: 1362
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Favorable functional outcome
timeFrame: at 90 days after randomization
measure: Incidence of severe adverse event (Safety outcome)
timeFrame: at 90 days after randomization
Secondary outcomes:
measure: Excellent functional outcome
timeFrame: at 90 days after randomization
measure: NIHSS score change
timeFrame: at 10-14 days after randomization
measure: NIHSS score decreases ≥4
timeFrame: at 10-14 days after randomization
measure: All-cause mortality
timeFrame: at 90 days after randomization
measure: Symptomatic intracranial hemorrhage (sICH)
timeFrame: at 24-36 hours after randomization
measure: Neurological deterioration
timeFrame: at day 1 after randomization
measure: Stroke recurrence
timeFrame: within 90 days after randomization
measure: Adverse events (AE)
timeFrame: within 90 days after randomization
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital, Capital Medical University
state: Beijing
Study officials:
affiliation: Beijing Tiantan Hospital
name: Yongjun Wang, MD.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hill MD, Goyal M, Menon BK, Nogueira RG, McTaggart RA, Demchuk AM, Poppe AY, Buck BH, Field TS, Dowlatshahi D, van Adel BA, Swartz RH, Shah RA, Sauvageau E, Zerna C, Ospel JM, Joshi M, Almekhlafi MA, Ryckborst KJ, Lowerison MW, Heard K, Garman D, Haussen D, Cutting SM, Coutts SB, Roy D, Rempel JL, Rohr AC, Iancu D, Sahlas DJ, Yu AYX, Devlin TG, Hanel RA, Puetz V, Silver FL, Campbell BCV, Chapot R, Teitelbaum J, Mandzia JL, Kleinig TJ, Turkel-Parrella D, Heck D, Kelly ME, Bharatha A, Bang OY, Jadhav A, Gupta R, Frei DF, Tarpley JW, McDougall CG, Holmin S, Rha JH, Puri AS, Camden MC, Thomalla G, Choe H, Phillips SJ, Schindler JL, Thornton J, Nagel S, Heo JH, Sohn SI, Psychogios MN, Budzik RF, Starkman S, Martin CO, Burns PA, Murphy S, Lopez GA, English J, Tymianski M; ESCAPE-NA1 Investigators. Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): a multicentre, double-blind, randomised controlled trial. Lancet. 2020 Mar 14;395(10227):878-887. doi: 10.1016/S0140-6736(20)30258-0. Epub 2020 Feb 20.
citation: Xu J, Wang A, Meng X, Yalkun G, Xu A, Gao Z, Chen H, Ji Y, Xu J, Geng D, Zhu R, Liu B, Dong A, Mu H, Lu Z, Li S, Zheng H, Chen X, Wang Y, Zhao X, Wang Y; TASTE Trial Investigatorsdagger. Edaravone Dexborneol Versus Edaravone Alone for the Treatment of Acute Ischemic Stroke: A Phase III, Randomized, Double-Blind, Comparative Trial. Stroke. 2021 Mar;52(3):772-780. doi: 10.1161/STROKEAHA.120.031197. Epub 2021 Feb 16.