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

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Ischemic Stroke; Mechanical Thrombectomy; Edaravone Dexborneol; Phase III
• Intervention / Treatment: Drug: Edaravone Dexborneol Concentrated Solution for injection; Drug: Edaravone Dexborneol placebo

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 Type: Interventional
• Enrollment (Actual): 1362
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100070
      • Beijing Tiantan Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Edaravone Dexborneol group; 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; 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.; Other Names: Xian Bi Xin, CFDA Approval Number H20200007
Placebo Comparator: Edaravone Dexborneol Placebo group; 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; Edaravone and Dexborneol placebo, 15 ml in 3 ampoule bottles, twice a day for 10 to 14 days.; Other Names: Xian Bi Xin placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Investigators: Principal Investigator: Yongjun Wang, MD., Beijing Tiantan Hospital

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2022
• Primary Completion (Actual): February 17, 2023
• Study Completion (Actual): May 19, 2023

Study Registration Dates

• First Submitted: January 25, 2022
• First Submitted That Met QC Criteria: February 21, 2022
• First Posted (Actual): February 22, 2022

Study Record Updates

• Last Update Posted (Actual): August 22, 2023
• Last Update Submitted That Met QC Criteria: August 20, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neuroprotective Agents; Protective Agents; Antioxidants; Free Radical Scavengers; Edaravone
• Other Study ID Numbers: NCRC-2021-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No