EcLiPSE

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Lyttle MD. "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.
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Clinical Question

In paediatric patients that present with status epilepticus, following first-line benzodiazepines, how does levetiracetam compare to phenytoin for second line therapy?

Bottom Line

There was no difference for second line therapy with levetiracetam compared to phenytoin and levetiracetam may have advantages such as faster infusion time and fewer adverse effects.

Major Points

Guidelines

As of June 2018, no guidelines have been published that reflect the results of this trial.

Design

  • Multicenter, open-lable, randomized, controlled trial
  • N=296
    • Levetiracetam (n=152)
    • Phenytoin (n=134)
  • Setting: 30 Emergency Departments in the UK
  • Enrollment: 17July2015 to 7Apr2018
  • Mean follow-up:
  • Analysis: modified Intention-to-Treat
  • Primary Outcome: time from randomization to cessation of seizure

Population

Inclusion Criteria

  • age 6 months to 18 years
  • presenting with convulsive status epilepticus (generalised tonic-clonic, generalized clonic, or focal clonic seizure) requiring second line therapy

Exclusion Criteria

  • presented with absence, myoclonic, or non-convulsive status epilepticus, or infantile spasms
  • known or suspected to be pregnant
  • Contraindication or allergy to study drugs
  • established renal failure
  • received a second-line anticonvulsant during the presenting episode of convulsive status epilepticus before screening
  • previously enrolled in the trial

Baseline Characteristics

Levetiracetam Group displayed

  • Demographics: 51% female, 45% first seizure at presentation
  • Age: 43% 6months-2years, 53% 2-11years, 4% 12-17years
  • Weight: 34% <12 kg, 57% 12-36 kg,
  • Seizure type: 70% generalized tonic-clonic, 8% generalized clonic, 22% focal clonic
  • Seizure cause: 41% febrile, 30% pre-existing seizure disorder, 4% CNS infection, 7% indeterminate, 18% other
  • Maintenance medications at presentation: levetiracetam 19%, valproate 11%, carbamazepine 8%, clobazam 6%, topiramate 3%, phenytoin 0%, other 7%

Interventions

  • Levetiracetam 40 mg/kg over 5 minutes (maximum 2500mg)
  • Phenytoin 20 mg/kg over 20 minutes (maximum 2000mg)

Outcomes

Comparisons are levetiracetam vs. phenytoin.

Primary Outcomes

Time from randomization to seizure cessation, median
35 min vs. 45 min (HR 1.2, 95% CI 0.91-1.60) P = 0.20

Secondary Outcomes

Termination of status-epilepticus
70% vs. 64%
Time to initiation of study drug infusion
11 min vs. 12 min
Receipt of additional anticonvulsants
38% vs. 37% (RR 1.01, 95% CI 0.74-1.36) P = 0.97
Patients receiving Rapid Sequence Intubation (RSI) due to ongoing seizure activity
29% vs. 35% (RR 0.83, 95% CI 0.59–1.16) P = 0.27

Subgroup Analysis

Adverse Events

Any adverse event
11% vs. 13%

Criticisms

Funding

Further Reading