Seizure prophylaxis in glioma surgery (SPRING): A multi-center, unblinded, randomized trial

50%-80% of glioma patients will have seizures. Guidelines recommend against prophylactic anti-seizure medication, but levetiracetam is frequently prescribed. Our aim was to determine the effectiveness of 12-month prophylactic levetiracetam at reducing seizure risk.

Seizure-naïve patients undergoing glioma surgery were randomized (1:1) to 12-month levetiracetam or no prophylaxis and followed until death or a maximum of 18-months. The primary outcome was 1-year risk of first seizure. Patients who died within 12 months of randomization without experiencing a seizure were excluded from the primary outcome analysis. Target accrual was 804 participants. The trial was registered (ISRCTN 49474281 and EudraCT 2018-001312-30).

Between October 10, 2019 and August 30, 2022, 96 patients, from 24 to 79 years of age, were randomized to levetiracetam (n = 49) or no prophylaxis (n = 47). The trial closed early due to slow accrual and the Covid pandemic. In the levetiracetam group, 17 patients had a seizure and 32 did not (19 survived ≥12 months, 13 died within 12 months). In the no-prophylaxis group, 15 patients had a seizure and 30 did not (21 survived ≥12 months, 9 died within 12 months). Seventeen of the 36 evaluable levetiracetam patients (47%) had a seizure, compared with 15 of 36 evaluable no-prophylaxis patients (41%) (OR: 1.25, 95% CI, 0.49-3.21, P = .64). There were no levetiracetam-related serious adverse events.

The seizure prophylaxis in glioma surgery (SPRING) trial provides no evidence of a difference between levetiracetam and no prophylaxis in the 12-month seizure risk in patients undergoing glioma surgery, but the study was underpowered. The role of prophylactic anti-seizure medication remains undefined.