Edaravone dexborneol versus placebo on functional outcomes in patients with acute ischaemic stroke undergoing endovascular thrombectomy (TASTE-2): randomised controlled trial

Abstract

Objective: To assess the efficacy and safety of edaravone dexborneol, a multitarget brain cytoprotectant composed of antioxidant and anti-inflammatory ingredients, in improving functional outcomes among patients with acute ischaemic stroke undergoing endovascular thrombectomy.

Design: Multicentre, double blind, randomised, placebo controlled trial.

Setting: 106 hospitals in China between March 2022 and May 2023.

Participants: 1362 patients with clinically diagnosed acute ischaemic stroke within 24 hours of symptom onset, aged 18-80 years, with a National Institutes of Health Stroke Scale (NIHSS) score of 6-25 and an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 6-10, confirmed large vessel occlusion in the anterior circulation, and planned endovascular thrombectomy.

Interventions: Patients were randomly allocated in a 1:1 ratio to receive edaravone dexborneol 37.5 mg (edaravone, 30 mg; (+)-dexborneol, 7.5 mg; 690 patients) or placebo (672 patients) before endovascular thrombectomy and continued the regimen twice daily for a consecutive period of 10-14 days.

Main outcome measures: Functional independence at 90 days, defined as a modified Rankin Scale score (range 0 (no symptoms) to 6 (death)) of 0-2, and serious adverse events.

Results: One patient from each group was lost to follow-up at 90 days. Of the 1360 patients included in the intention-to-treat analysis, 379 (55.0%) of 689 patients in the edaravone dexborneol group and 333 (49.6%) of 671 patients in the placebo group achieved functional independence on day 90 (risk ratio 1.11, 95% confidence interval (CI) 1.00 to 1.23; P=0.05; risk difference 5.4%, 95% CI 0.1% to 10.7%). Patients with mismatch at admission (defined as NIHSS score ≥10 and ASPECTS ≥9 or NIHSS score ≥20 and ≥7) were more likely to achieve functional independence in the subgroup analysis (55.5% (178/321) versus 42.9% (134/312); risk ratio 1.29, 1.10 to 1.52; risk difference 13.0%, 5.6% to 20.3%; P for interaction=0.003). The rates of serious adverse events were similar in the two groups (27.2% (188/690) versus 25.7% (173/672); risk ratio 1.06, 0.89 to 1.26; risk difference 1.5%, -3.2% to 6.2%: P=0.53).

Conclusions: Among patients with acute ischaemic stroke within 24 hours of symptom onset who underwent endovascular thrombectomy, those treated with edaravone dexborneol, compared with placebo, were more likely to achieve functional independence at 90 days without increased safety concerns. This effect seemed to be primarily driven by the subgroup with mismatch present at admission, suggesting that dedicated trials in this population may be warranted.

Trial registration: ClinicalTrials.gov NCT05249920.

Fig 1

Trial profile. EVT=endovascular thrombectomy

Fig 2

Modified Rankin Scale score at 90 days. Scores on modified Rankin Scale are shown for patients in edaravone dexborneol group (n=689) and placebo group (n=671). Scores range from 0 to 6, with 0 indicating no symptoms; 1, no clinically significant disability; 2, slight disability (able to handle own affairs without assistance but unable to carry out all previous activities); 3, moderate disability (requiring some help but able to walk unassisted); 4, moderately severe disability (unable to attend body needs and unable to walk); 5, severe disability (requiring constant nursing care and attention); and 6, death. Treatment with edaravone dexborneol was likely to achieve functional independence (score of 0- 2 on modified Rankin Scale) at 90 days, with risk ratio of 1.11 (95% confidence interval 1.00 to 1.23) and risk difference of 5.4% (0.1% to 10.7%) (P=0.05). An interactive version of this graphic and downloadable data are available at https://public.flourish.studio/visualisation/26783154/

Fig 3

Primary outcome by pre-specified subgroups (relative risks). Significantly greater likelihood of achieving functional independence with edaravone dexborneol, compared with placebo, was observed in predefined subgroups of ASPECTs and mismatch (defined as NIHSS score ≥10 and ASPECTS ≥9 or NIHSS score ≥20 and ASPECTS ≥7), with P for interaction <0.05. An interactive version of this graphic and downloadable data are available at https://public.flourish.studio/visualisation/26783332/

Fig 4

Primary outcome by pre-specified subgroups (risk differences). Significantly greater likelihood of achieving functional independence with edaravone dexborneol, compared with placebo, was observed in predefined subgroups of ASPECTs and mismatch (defined as NIHSS score ≥10 and ASPECTS ≥9 or NIHSS score ≥20 and ASPECTS ≥7), with P for interaction <0.05. An interactive version of this graphic and downloadable data are available at https://public.flourish.studio/visualisation/26824711/