Sublingual Edaravone Dexborneol for the Treatment of Acute Ischemic Stroke (TASTE-SL): A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial

Background: Sublingual edaravone dexborneol, which can be rapidly permeated and absorbed through the oral mucosa after sublingual exposure, is a multitarget brain cytoprotection comprised of antioxidant and anti-inflammatory ingredients of edaravone and dexborneol. This study aimed to investigate the efficacy and safety of sublingual edaravone dexborneol on 90-day functional outcome in patients with AIS.Methods: We conducted a randomized, double-blind, placebo-controlled, multicenter, parallel-group phase III trial at 33 centers in China involving patients with AIS. Patients were assigned within 48 hours after symptom onset, in a 1:1 ratio, to receive sublingual edaravone dexborneol (edaravone 30mg, dexborneol 6mg) or placebo (edaravone 0 mg, dexborneol: 60 μg) twice daily for 14 days and were followed up until 90 days. The primary efficacy outcome was the proportion of patients with modified Rankin Scale score ≤1 on day 90 after randomization. This trial is registered with ClinicalTrials.gov (NCT04950920).Findings: A total of 914 patients were randomly allocated to the edaravone dexborneol group (n=450) or placebo (n=464). The edaravone dexborneol group showed a significantly higher proportion of patients experiencing good function functional outcomes on day 90 after randomization, compared with the placebo group (64.4% versus 54.7%; risk difference, 9.70%; 95% confidence interval, 3.37%-16.03%; odds ratio, 1.50; 95% confidence interval, 1.15-1.95, P=0.003). The rate of adverse event was similar between the two groups (89.8% versus 90.1%).Interpretation: 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 the placebo.Trial Registration: This trial is registered with ClinicalTrials.gov (NCT04950920).Funding: Simcere Pharmaceutical Co., Ltd.Declaration of Interest: RT, JR, SZ and XF are the employees of Simcere Pharmaceutical Group; SY and RC is the employee of Neurodawn Pharmaceutical. Those companies have developed the drug and sponsored the trial. The above-mentioned five authors from companies provided information on the pharmacological mechanism of drugs, gave preclinical experimental data and advised on study design. No other competing interests were reported.Ethical Approval: The study was conducted in accordance with the principles of the Declaration of Helsinki. The ethics committee from each study center approved this study, and all patients or their legally acceptable surrogates had given informed consents before they were assigned to a treatment group.