Eslicarbazepine Antiepileptogenesis
(2026)Objective
To assess whether eslicarbazepine acetate prevents post-stroke epilepsy in patients at high risk after acute stroke.
Study Summary
• Incidence of epilepsy at 18 months was low and similar (3% vs 5%)
• The proof-of-concept trial was underpowered (slow recruitment, COVID-19 disruption) but eslicarbazepine was generally well tolerated
Intervention
Eslicarbazepine acetate 800 mg/day vs matching placebo for 6 months; N=127
Inclusion Criteria
Age 18-85 years with acute ischemic or hemorrhagic stroke within 72 hours, supratentorial cortical involvement, NIHSS ≥4, no prior seizure history.
Study Design
Arms: Eslicarbazepine Acetate vs Placebo (control)
Patients per Arm: Eslicarbazepine: 62, Placebo: 63
Outcome
• Epilepsy at 18 months: 3% vs 5%
• TEAEs ~82% in both groups; hyponatremia 8% vs 2%
• 5 deaths in the eslicarbazepine group, none related to study drug
Bottom Line
Eslicarbazepine acetate did not significantly reduce the composite endpoint of first unprovoked seizure, death, or treatment discontinuation compared to placebo in post-stroke patients (28% vs 37%, OR 0.66, p=0.37). The trial was underpowered due to slow recruitment and COVID-19 disruptions but demonstrates the feasibility of conducting antiepileptogenesis trials.
Major Points
- Eslicarbazepine did NOT prevent post-stroke seizures: primary composite (first seizure/death/discontinuation) 28% vs 37% (OR 0.69; 95% CI 0.32-1.46; P=0.34).
- Incidence of epilepsy at 18 months: 3% (eslicarbazepine) vs 5% (placebo) — NS.
- First randomized trial of antiepileptogenesis after stroke.
- 127 patients randomized (eslicarbazepine 800mg/day vs placebo for 6 months). 20 European centers.
- Eslicarbazepine well tolerated: discontinuation for AEs similar between groups.
- Proof-of-concept study — underpowered for definitive antiepileptogenesis conclusion.
- Supratentorial cortical stroke with NIHSS ≥4 enriched for post-stroke epilepsy risk.
- Post-stroke epilepsy is common (5-10% at 5 years) but no proven preventive therapy exists.
- Published Lancet Neurology 2023. Phase 2 trial.
- Supports need for larger antiepileptogenesis trials with longer follow-up.
Study Design
- Study Type
- Randomized, double-blind, placebo-controlled, phase 2 trial
- Randomization
- Yes
- Blinding
- Double-blind
- Sample Size
- 127
- Follow-up
- 18 months
- Centers
- 20
- Countries
- Multiple European countries
Primary Outcome
Definition: Composite of first unprovoked seizure, death, or treatment discontinuation at 6 months
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| - | - | 0.66 | 0.37 |
Limitations & Criticisms
- Underpowered due to slow recruitment and COVID-19 pandemic disruption
- 6-month follow-up may be insufficient to detect antiepileptogenic effects
- Composite primary endpoint includes treatment discontinuation which may not reflect true antiepileptogenesis
Citation
Koepp MJ, Trinka E et al. Lancet Neurol. 2026;25(3):256-267. DOI: 10.1016/S1474-4422(25)00491-0