Edaravone dexborneol versus placebo on functional outcomes in patients with acute ischaemic stroke undergoing...

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.

Multicentre, double blind, randomised, placebo controlled trial.

106 hospitals in China between March 2022 and May 2023.

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.

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.

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.

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).

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.

ClinicalTrials.gov NCT05249920.