Potential Stroke Therapy Is Deemed Ineffective
Authors of a new study report that S44819—a selective GABAA α5 receptor antagonist—cannot be recommended for stroke therapy. This determination comes after the researchers found no evidence that S44819 improved patients’ clinical outcome following ischemic stroke.
These findings come from the Randomized Efficacy and Safety Trial of Oral GABAA α5 antagonist S44819 after Recent ischemic Event (RESTORE BRAIN) study. To reach their conclusions, the study authors evaluated the safety and efficacy of oral S44819 for enhancing clinical recovery among 585 patients who had recently had ischemic stroke.
Enrollment for the Phase 2 trial had taken place between December 19, 2016, and November 16, 2018. To be eligible, patients had to have been aged 18 to 85 years with acute ischemic stroke involving cerebral cortex (National Institute of Health Stroke Scale [NIHSS] score 7-20) without previous disability.
The study was conducted in specialized stroke units in 92 actively recruiting centers in 14 countries.
At a 1:1:1 ratio, participants were randomly assigned to receive S44819, 150 mg (n=197); S44819, 300 mg (n=195); or placebo (n=193). All doses were taken twice daily.
The efficacy analyses included the 568 participants who had received at least 1 dose of treatment and had at least 1 modified Rankin Scale (mRS) score taken after day 5.
The primary endpoint of mRS score at day 90 did not differ between the 3 groups. Dichotomised mRS scores also did not differ between the groups.
Secondary endpoints were the effects of S44819 on the NIHSS and Montreal Cognitive Assessment scores, time needed to complete parts A and B of the Trail Making Test, and the Barthel index. None of the secondary endpoint results significantly differed between the groups either.
The safety analysis included the 582 participants who had received at least 1 dose of treatment. The analysis revealed a similarity between the groups in terms of the number and type of adverse events. No drug-related adverse events and no drug-related deaths were reported.
Chabriat H, Bassetti CL, Marx U, et al; RESTORE BRAIN study investigators. Safety and efficacy of GABAA α5 antagonist S44819 in patients with ischaemic stroke: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2020;19(3):226-233. https://doi.org/10.1016/S1474-4422(20)30004-1.