Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus
- PMID: 31774955
- PMCID: PMC7098487
- DOI: 10.1056/NEJMoa1905795
Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus
Abstract
Background: The choice of drugs for patients with status epilepticus that is refractory to treatment with benzodiazepines has not been thoroughly studied.
Methods: In a randomized, blinded, adaptive trial, we compared the efficacy and safety of three intravenous anticonvulsive agents - levetiracetam, fosphenytoin, and valproate - in children and adults with convulsive status epilepticus that was unresponsive to treatment with benzodiazepines. The primary outcome was absence of clinically evident seizures and improvement in the level of consciousness by 60 minutes after the start of drug infusion, without additional anticonvulsant medication. The posterior probabilities that each drug was the most or least effective were calculated. Safety outcomes included life-threatening hypotension or cardiac arrhythmia, endotracheal intubation, seizure recurrence, and death.
Results: A total of 384 patients were enrolled and randomly assigned to receive levetiracetam (145 patients), fosphenytoin (118), or valproate (121). Reenrollment of patients with a second episode of status epilepticus accounted for 16 additional instances of randomization. In accordance with a prespecified stopping rule for futility of finding one drug to be superior or inferior, a planned interim analysis led to the trial being stopped. Of the enrolled patients, 10% were determined to have had psychogenic seizures. The primary outcome of cessation of status epilepticus and improvement in the level of consciousness at 60 minutes occurred in 68 patients assigned to levetiracetam (47%; 95% credible interval, 39 to 55), 53 patients assigned to fosphenytoin (45%; 95% credible interval, 36 to 54), and 56 patients assigned to valproate (46%; 95% credible interval, 38 to 55). The posterior probability that each drug was the most effective was 0.41, 0.24, and 0.35, respectively. Numerically more episodes of hypotension and intubation occurred in the fosphenytoin group and more deaths occurred in the levetiracetam group than in the other groups, but these differences were not significant.
Conclusions: In the context of benzodiazepine-refractory convulsive status epilepticus, the anticonvulsant drugs levetiracetam, fosphenytoin, and valproate each led to seizure cessation and improved alertness by 60 minutes in approximately half the patients, and the three drugs were associated with similar incidences of adverse events. (Funded by the National Institute of Neurological Disorders and Stroke; ESETT ClinicalTrials.gov number, NCT01960075.).
Copyright © 2019 Massachusetts Medical Society.
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Comment in
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Management of Established Status Epilepticus.N Engl J Med. 2019 Nov 28;381(22):2171-2172. doi: 10.1056/NEJMe1913775. N Engl J Med. 2019. PMID: 31774965 No abstract available.
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Second-line anticonvulsant for convulsive status epilepticus: The dosage matters!Anaesth Crit Care Pain Med. 2020 Feb;39(1):11-13. doi: 10.1016/j.accpm.2019.12.007. Epub 2020 Jan 2. Anaesth Crit Care Pain Med. 2020. PMID: 31904430 No abstract available.
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[Focus neurological intensive care medicine : Intensive medical care studies from 2019/2020].Anaesthesist. 2021 Feb;70(2):164-170. doi: 10.1007/s00101-020-00861-z. Anaesthesist. 2021. PMID: 33051691 Free PMC article. German. No abstract available.
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Comparison of three anticonvulsive agents for benzodiazepine resistant status epilepticus.CJEM. 2021 Jan;23(1):29-31. doi: 10.1007/s43678-020-00021-7. Epub 2020 Dec 10. CJEM. 2021. PMID: 33683605 No abstract available.
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