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Eslicarbazepine Antiepileptogenesis

Safety and efficacy of eslicarbazepine acetate for seizure prevention in patients with stroke at high risk of developing post-stroke epilepsy: a proof-of-concept, phase 2a, randomised, double-blind, placebo-controlled antiepileptogenesis trial

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Year of Publication: 2026

Authors: Koepp MJ, Trinka E et al.

Journal: Lancet Neurology

Citation: Koepp MJ, Trinka E et al. Lancet Neurol. 2026;25(3):256-267. DOI: 10.1016/S1474-4422(25)00491-0

Link: https://doi.org/10.1016/S1474-4422(25)00491-0

Clinical Question

Can eslicarbazepine acetate prevent the development of post-stroke epilepsy in patients at high risk after acute stroke?

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.

Design

Study Type: Randomized, double-blind, placebo-controlled, phase 2 trial

Randomization: 1

Blinding: Double-blind

Enrollment Period: 2018-2021

Follow-up Duration: 18 months

Centers: 20

Countries: Multiple European countries

Sample Size: 127

Analysis: Intention-to-treat

Inclusion Criteria

  • Age 18-85 years.
  • Acute ischemic or hemorrhagic stroke within previous 72 hours.
  • Supratentorial cortical involvement on imaging.
  • NIHSS ≥4.
  • No prior seizure history.

Exclusion Criteria

  • Known epilepsy or prior unprovoked seizures.
  • Prior treatment with antiseizure medications.
  • Severe renal or hepatic impairment.
  • Pregnancy.

Arms

FieldEslicarbazepine AcetateControl
n6263
InterventionEslicarbazepine acetateMatching placebo

Outcomes

OutcomeTypeControlInterventionHR / OR / RRP-value
Composite of first unprovoked seizure, death, or treatment discontinuation at 6 monthsPrimary0.660.37
82% both groupsAdverse
8% eslicarbazepine vs 2% placeboAdverse
5 in eslicarbazepine group (unrelated to study medication)Adverse

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

Funding

BIAL (pharmaceutical company)

Based on: Eslicarbazepine Antiepileptogenesis (Lancet Neurology, 2026)

Authors: Koepp MJ, Trinka E et al.

Citation: Koepp MJ, Trinka E et al. Lancet Neurol. 2026;25(3):256-267. DOI: 10.1016/S1474-4422(25)00491-0

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