medwireNews: Treating acute ischemic stroke (AIS) patients with sublingual edaravone dexborneol within 48 hours of symptom onset improves the odds of favorable functional outcomes at 90 days compared with placebo, reports the TASTE-SL study.
In the double-blind, placebo-controlled, phase 3 trial conducted between 2021 and 2022 across 33 centers in China, Dongsheng Fan (Peking University Third Hospital, Beijing, China) and colleagues explored the use of the sublingual cytoprotective agent, which combines antioxidant and anti-inflammatory agents, as an easier-to-access formulation than intravenous edaravone dexborneol.
The study included 914 patients with AIS, aged 18 to 80 years (mean 64 years), who had a median National Institutes of Health Stroke Scale (NIHSS) score of 7 points, a modified Rankin Scale (mRS) score before the stroke of 1 point or lower (91.7% had a score of 0 points), a total motor deficit score of the upper and lower limbs of 2 points or greater, and were clinically diagnosed with AIS within 48 hours of symptom onset. All of the participants were of Chinese Han ethnicity.
Fan and colleagues randomly assigned 450 patients to receive sublingual edaravone 30 mg plus dexborneol 6 mg twice daily for 14 days and 464 to receive placebo (containing 6 μg of dexborneol to mimic the taste of the combination agent). Concomitant treatments were continued as usual.
A significantly greater proportion of patients receiving edaravone dexborneol than placebo had an mRS score of 1 or less at 90 days, at 64.4% versus 54.7%, and an odds ratio for the favorable outcome of 1.50.
Subgroup analyses showed that the beneficial effect of edaravone dexborneol remained consistent irrespective of sex, age above or below 65 years, and whether patients had a history of stroke, hypertension, hyperlipidemia, diabetes, or heart disease.
However, there was no significant difference between edaravone dexborneol and placebo for secondary outcomes, such as the proportion of patients with an mRS score of 2 points or below, and the change in NIHSS score from baseline to day 14, which the investigators say is likely due to the majority of patients having a relatively low NIHSS score.
Adverse events were similar across the two groups, occurring in 89.8% of patients in the edaravone dexborneol arm and 90.1% of those in the placebo arm. Treatment-related adverse events within the 90-day period also did not differ significantly, at respective rates of 13.6% and 10.8%.
In an editorial related to the study in JAMA Neurology, Craig Anderson (University of New South Wales, Sydney, Australia) and Lili Song (The George Institute Beijing) say that the findings are “remarkable,” and have “major potential practice implications,” given that “edaravone dexborneol is low cost, simple to administer (even in patients who are unconscious, disabled, or dysphagic), and readily available in China.”
However, they question the size of the effect, which “is much higher than would be expected of a neuroprotective agent,” commenting that the trial was powered at 80% rather than the conventional 90% and that the primary outcome findings were “inconsistent with the lack of any improvement in early neurological impairment, according to change in National Institutes of Health Stroke Scale scores between baseline and 14 and 30 days.”
Nevertheless, the editorialists conclude that the findings “provide a clear justification for further evaluations of edaravone dexborneol in other populations and for individual patient data meta-analysis to be undertaken to determine the totality of the evidence.”
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JAMA Neurology 2024; doi:10.1001/jamaneurol.2023.5716
JAMA Neurology 2024; doi:10.1001/jamaneurol.2023.5727