Sublingual Edaravone Dexborneol for the Treatment of Acute Ischemic Stroke: The TASTE-SL Randomized Clinical Trial

Abstract

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: NCT04950920.

Figure 1.. Enrollment and Randomization of the Patients

The prohibited concomitant medications included drugs with indications of neuroprotection or cerebral infarction and unmarketed drugs or other drugs for clinical trials.

Figure 2.. Distribution of Functional Outcomes at 90 Days in the Intention-to-Treat Population

Shown are scores on the modified Rankin Scale (mRS) for the patients in the 2 treatment groups. Scores range from 0 to 6, with 0 indicating no symptoms; 1, no clinically significant disability; 2, slight disability (patients are able to look after their own affairs without assistance but are unable to carry out all previous activities); 3, moderate disability (patients require some help but are able to walk unassisted); 4, moderately severe disability (patients are unable to attend to bodily needs without assistance and are unable to walk unassisted); 5, severe disability (patients require constant nursing care and attention); and 6, death. Missing data on mRS was considered to be 6 for patients without at least 1 postbaseline measurement of mRS (8 patients in the edaravone dexborneol group, and 8 in the placebo group), or discontinued treatment or follow-up due to adverse events (8 and 14), and the last observation carried forward approach was used for patients who had at least 1 valid postbaseline measurement (24 and 10).

Figure 3.. Subgroup Analysis for the Primary Analysis

mRS indicates modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; OR, odds ratio; TOAST, Trial of Org 10172 in Acute Stroke Treatment.