Sublingual Edaravone Dexborneol for the Treatment of Acute Ischemic Stroke
Yu Fu, Anxin Wang, Renhong Tang, Shuya Li, Xue Tian, Xue Xia, Jinsheng Ren, Shibao Yang, Rong Chen, Shunwei Zhu, Xiaofei Feng, Jinliang Yao, Yan Wei, Xueshuang Dong, Yun Ling, Fei Yi, Qian Deng, Cunju Guo, Yi Sui, Shugen Han, Guoqiang Wen, Chuanling Li, Aiqin Dong, Xin Sun, Zhimin Wang, Xueying Shi, Bo Liu, Dongsheng Fan- Neurology (clinical)
Importance
Sublingual edaravone dexborneol, which can rapidly diffuse and be absorbed through the oral mucosa after sublingual exposure, is a multitarget brain cytoprotection composed of antioxidant and anti-inflammatory ingredients edaravone and dexborneol.
Objective
To investigate the efficacy and safety of sublingual edaravone dexborneol on 90-day functional outcome in patients with acute ischemic stroke (AIS).
Design, Setting, and Participants
This was a double-blind, placebo-controlled, multicenter, parallel-group, phase 3 randomized clinical trial conducted from June 28, 2021, to August 10, 2022, with 90-day follow-up. Participants were recruited from 33 centers in China. Patients randomly assigned to treatment groups were aged 18 to 80 years and had a National Institutes of Health Stroke Scale score between 6 and 20, a total motor deficit score of the upper and lower limbs of 2 or greater, a clinically diagnosed AIS symptom within 48 hours, and a modified Rankin Scale (mRS) score of 1 or less before stroke. Patients who did not meet the eligibility criteria or declined to participate were excluded.
Intervention
Patients were assigned, in a 1:1 ratio, to receive sublingual edaravone dexborneol (edaravone, 30 mg; dexborneol, 6 mg) or placebo (edaravone, 0 mg; dexborneol, 60 μg) twice daily for 14 days and were followed up until 90 days.
Main Outcomes and Measures
The primary efficacy outcome was the proportion of patients with mRS score of 1 or less on day 90 after randomization.
Results
Of 956 patients, 42 were excluded. A total of 914 patients (median [IQR] age, 64.0 [56.0-70.0] years; 608 male [66.5%]) were randomly allocated to the edaravone dexborneol group (450 [49.2%]) or placebo group (464 [50.8%]). The edaravone dexborneol group showed a significantly higher proportion of patients experiencing good functional outcomes on day 90 after randomization compared with the placebo group (290 [64.4%] vs 254 [54.7%]; risk difference, 9.70%; 95% CI, 3.37%-16.03%; odds ratio, 1.50; 95% CI, 1.15-1.95, P = .003). The rate of adverse events was similar between the 2 groups (89.8% [405 of 450] vs 90.1% [418 of 464]).
Conclusion and Relevance
Among patients with AIS within 48 hours, sublingual edaravone dexborneol could improve the proportion of those achieving a favorable functional outcome at 90 days compared with placebo.
Trial Registration
ClinicalTrials.gov Identifier: