Presentation
Efficacy and Safety of Intravenous Ganaxolone for Treatment of Refractory Status Epilepticus: Results from the Phase 3, Double-Blind, Randomized, Placebo-Controlled RAISE Trial
Description
Background and Purpose: Ganaxolone is a positive modulator of synaptic and extrasynaptic GABAA receptors and was effective in an open-label Phase 2 study of refractory status epilepticus (RSE). We conducted a randomized, placebo-controlled trial (NCT04391569) to evaluate the efficacy and safety of intravenous (IV) ganaxolone in RSE. Methods: Patients 12 years of age and older with RSE who had failed ≥2 SE treatments were eligible for enrollment. The co-primary endpoints were the proportion of patients with SE cessation within 30 minutes without additional SE medications and no progression to IV anesthesia (IVA) within 36 hours. Results: 100 patients were randomized 1:1 to receive IV ganaxolone (n=51) or placebo (n=49) added to standard of care; 96 were included in the intent-to-treat analysis. Most (73%) had SE without prominent motor symptoms and had failed a median of 3 [interquartile range (IQR) 2-4] antiseizure medications. SE stopped within 30 minutes in 80% of patients receiving ganaxolone versus 13% for placebo, (p<0.0001). The median time to SE cessation was 4.2 [IQR 1.2-10.8] minutes with ganaxolone. There was no 36-hour progression to IVA in 63% of ganaxolone- versus 51% of placebo-treated patients, p=0.162. Proportion of patients with no escalation of treatment within 24 hours favored ganaxolone (45% versus 19%) as did reduction in EEG seizure burden. Serious treatment-emergent adverse events were similar between groups other than hypotension (9.8% versus 2.0% for ganaxolone and placebo, respectively). Conclusion: IV ganaxolone produced rapid SE cessation but did not show a statistically significant difference in escalation to IVA despite a reduction in EEG seizure burden. Avoiding progression to IVA use was confounded by intercurrent clinical and treatment factors and therefore not a valid proxy for SE cessation. Escalation of care with any SE treatment and reduction in EEG seizure burden may represent potential endpoints for future trials.Event Type
Late-Breaking Abstract
TimeThursday, October 17th9:35am - 9:55am PDT
LocationHarbor Ballrooms B-C
Science of Neurocritical Care
Head and Spine Trauma
Seizures/EEG
Curing Coma
Intermediate