美国密歇根大学Robert Silbergleit课题组进行了一项三种抗惊厥药物治疗癫痫持续状态的随机试验。这一研究成果发表在11月28日出版的《新英格兰医学杂志》上。

据悉，对于苯二氮卓类药物难治性癫痫持续状态患者如何用药尚未明确。

在这项随机、盲选、适应性试验中，研究组比较了三种静脉注射的抗惊厥药物：左乙拉西坦、磷苯妥英和丙戊酸钠，对苯二氮卓类治疗无效的儿童和成人惊厥性癫痫持续状态的疗效和安全性。

研究组共招募了384名患者，将其随机分组，其中145名接受左乙拉西坦，118名接受磷苯妥英，121名接受丙戊酸钠进行治疗。10%的患者确诊患有精神性癫痫。左乙拉西坦组中有68例（47%）患者在输注药物后60分钟内癫痫持续状态停止且意识水平有所改善，磷苯妥英组有53例（45%），丙戊酸钠组有56例（46%）。

三种药物最有效的后验概率分别为0.41、0.24和0.35。磷苯妥英组低血压和插管的发生率略高，左乙拉西坦组死亡率略高，但这些差异均不显著。

总之，对于苯二氮卓类难治性癫痫持续状态的患者，抗惊厥药物左乙拉西坦、磷苯妥英和丙戊酸钠分别可使半数患者在1小时内停止发作并提高意识，且三种药物的不良事件相差不大。

附：英文原文

Title: Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus

Author: Jaideep Kapur, M.B., B.S., Ph.D.,, Jordan Elm, Ph.D.,, James M. Chamberlain, M.D.,, William Barsan, M.D.,, James Cloyd, Pharm.D.,, Daniel Lowenstein, M.D.,, Shlomo Shinnar, M.D., Ph.D.,, Robin Conwit, M.D.,, Caitlyn Meinzer, Ph.D.,, Hannah Cock, M.D.,, Nathan Fountain, M.D.,, Jason T. Connor, Ph.D.,, and Robert Silbergleit, M.D.

Issue&Volume: 2019-11-27

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. opens in new tab.)

DOI: 10.1056/NEJMoa1905795

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1905795