Epilepsy

New treatment options for pediatric convulsive status epilepticus after failure of first-line benzodiazepines

There are limited options as second line treatment in convulsive status epilepticus (CSE), both in underage and adult populations with sufficient level of scientific evidence to be approved by regulatory institutions (Shorvon and Trinka, 2018).

There are limited options as second line treatment in convulsive status epilepticus (CSE), both in underage and adult populations with sufficient level of scientific evidence to be approved by regulatory institutions (Shorvon and Trinka, 2018).

Phenytoin is the current standard of care for second-line treatment of paediatric CSE after failure of first-line benzodiazepines, but is only effective in 60% of cases and is associated with considerable adverse effects. A newer anticonvulsant, levetiracetam, has some favorable characteristics with potentially better tolerability and efficacy.

ConSEPT was an open-label, multicentre, randomised controlled trial conducted in 13 emergency departments in Australia and New Zealand (Dalziel et al., 2019), while EcLiPSE was open-label, randomised clinical trial undertaken at 30 UK emergency departments at secondary and tertiary care centres (Lyttle et al., 2019).

The aim was to compare the efficacy and safety of phenytoin (given in a dose of 20 mg/kg in intravenous or intraosseous infusion over 20 min) and levetiracetam (40 mg/kg in intravenous or intraosseous infusion over 5 min) in pediatric population (children aged 3 months and 16 years in ConSEPT and 6 months and under 18 years in EcLiPSE) diagnosed with convulsive SE after failure of first-line benzodiazepines. Both studies were not powered to demonstrate superiority of levetiracetam but rather non-inferiority to phenytoin.

It was found in ConCEPT study that clinical cessation of seizure activity 5 min after completion of infusion of study drug occurred in 68 (60%) patients in the phenytoin group and 60 (50%) patients in the levetiracetam group (risk difference -9·2% [95% CI -21·9 to 3·5]; p=0·16). In EcLiPSE study, SE was terminated in 106 (70%) children in the levetiracetam group and in 86 (64%) in the phenytoin group. Median time from randomisation to cessation of convulsive SE was 35 min (IQR 20 to not assessable) in the levetiracetam group and 45 min (24 to not assessable) in the phenytoin group (p=0·20). There were no serious adverse events in both treatment arms related to any drug.

In conclusion, levetiracetam was not inferior to phenytoin for second-line management of paediatric convulsive status epilepticus.

More studies are needed to guide clinical practice especially with head to head comparisons between standard and new-generation drugs.

 

Key points:

  • Status epilepticus
  • treatment
  • children
  • levetiracetam
  • phenytoin

 

References:

Shorvon S, Trinka E. Regulatory aspects of status epilepticus. Epilepsia. 2018;59 Suppl 2:128-134.

Dalziel SR, Borland ML, Furyk J, Bonisch M, Neutze J, Donath S, Francis KL, Sharpe C, Harvey AS, Davidson A, Craig S, Phillips N, George S, Rao A, Cheng N, Zhang M, Kochar A, Brabyn C, Oakley E, Babl FE; PREDICT research network. Levetiracetam versus phenytoin for second-line treatment of convulsive status epilepticus in children (ConSEPT): an open-label, multicentre, randomized controlled trial. Lancet. 2019;393(10186):2135-2145.

Lyttle MD, Rainford NEA, Gamble C, Messahel S, Humphreys A, Hickey H, Woolfall K, Roper L, Noblet J, Lee ED, Potter S, Tate P, Iyer A, Evans V, Appleton RE; Paediatric Emergency Research in the United Kingdom & Ireland (PERUKI) collaborative. Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial. Lancet. 2019;393(10186):2125-2134.