Levetiracetam versus phenytoin for seizure prophylaxis during and early after craniotomy for brain tumours: a phase II prospective, randomised study.

Abstract

OBJECTIVE:

Phenytoin (PHT) is routinely used for seizure prophylaxis in patients with brain tumours during and after craniotomy, despite incomplete evidence. We performed a prospective, randomised study to investigate the significance of prophylactic use of levetiracetam (LEV), in comparison with PHT, for patients with supratentorial tumours in the perioperative period.

METHODS:

Patients were randomised to receive LEV, 500 mg/body every 12 h until postoperative day 7, or PHT, 15-18 mg/kg fosphenytoin followed by 125 mg PHT every 12 h until postoperative day 7. The primary end point was the occurrence of seizures, and secondary end points included the occurrence of haematological and non-haematological adverse events.

RESULTS:

One hundred and forty-six patients were randomised to receive LEV (n=73) or PHT (n=73). The incidence of seizures was significantly less in the LEV group (1.4%) compared with the PHT group (15.1%, p=0.005), suggesting benefit of LEV over PHT. The observed OR for being seizure free in the LEV prophylaxis group relative to the PHT group was 12.77 (95% CI 2.39 to 236.71, p=0.001). In a subgroup analysis of patients who did not have seizures before craniotomy, similar results were demonstrated: the incidence of seizures was 1.9% (LEV) and 13.8% (PHT, p=0.034), and OR was 8.16 (95% CI 1.42 to 154.19, p=0.015). LEV was completed in all cases, although PHT was withdrawn in five patients owing to liver dysfunction (1), skin eruption (2) and atrial fibrillation (2).

CONCLUSIONS:

Prophylactic use of LEV in the perioperative period is recommended because it is safe and significantly reduces the incidence of seizures in this period.

TRIAL REGISTRATION NUMBER:

UMIN13971.

• Authors: Toshihiko Iuchi, Kiyoto Kuwabara, Minako Matsumoto, Koichiro Kawasaki, Yuzo Hasegawa, Tsukasa Sakaida
• Journal: Journal of neurology, neurosurgery, and psychiatry (J Neurol Neurosurg Psychiatry) Vol. 86 Issue 10 Pg. 1158-62 (Oct 2015) ISSN: 1468-330X [Electronic] England
• PMID: 25511789 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Chemical References

• Anticonvulsants
• Levetiracetam
• Phenytoin
• Piracetam

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Anticonvulsants (adverse effects, therapeutic use)
• Brain Neoplasms (complications, surgery)
• Cohort Studies
• Craniotomy (adverse effects)
• Female
• Humans
• Levetiracetam
• Male
• Middle Aged
• Neurosurgical Procedures (adverse effects)
• Phenytoin (adverse effects, therapeutic use)
• Piracetam (adverse effects, analogs & derivatives, therapeutic use)
• Postoperative Complications (prevention & control)
• Prospective Studies
• Seizures (prevention & control)
• Treatment Outcome
• Young Adult