Randomized trial of lacosamide versus fosphenytoin for nonconvulsive seizures

• Type of Material: Article
• Authors: Aatif M. Husain, Duke University; Jong W. Lee, Harvard Medical School; Bradley J. Kolls, Duke University; Lawrence J. Hirsch, Yale University; Jonathan J. Halford, Medical University of South Carolina; Puneet K. Gupta, University of Texas Southwestern Medical Center; Yafa Minazad, Huntington Memorial Hospital; Jennifer M. Jones, Mission Health; Suzette M Laroche, Emory University; Susan T. Herman, Harvard Medical School; Christa B. Swisher, Duke University; Saurabh R. Sinha, Duke University; Adriana Palade, University of Louisville; Keith E. Dombrowski, Duke University; William B. Gallentine, Duke University; Cecil D. Hahn, Hospital for Sick Children; Elizabeth E. Gerard, Northwestern University; Manjushri Bhapkar, Duke Clinical Research Institute; Yuliya Lokhnygina, Duke Clinical Research Institute; M. Brandon Westover, Harvard Medical School
• Language: English
• Date: 2018-06-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 American Neurological Association
• Final Published Version (URL): http://dx.doi.org/10.1002/ana.25249
• Title of Journal or Parent Work: Annals of Neurology
• ISSN: 0364-5134
• Volume: 83
• Issue: 6
• Start Page: 1174
• End Page: 1185
• Grant/Funding Information: This study was funded by UCB through an Investigator Initiated Study grant.
• Keywords: CRITICALLY-ILL PATIENTS; LEVETIRACETAM; CONVULSIVE STATUS EPILEPTICUS; ELECTROENCEPHALOGRAPHY; Clinical Neurology; REFRACTORY STATUS EPILEPTICUS; INTENSIVE-CARE-UNIT; Neurosciences & Neurology; SODIUM VALPROATE; INTRAVENOUS LACOSAMIDE; Science & Technology; PHENYTOIN; Neurosciences; Life Sciences & Biomedicine; CONTINUOUS EEG
• Research Categories: Biology, Neuroscience

Abstract

Objective: The optimal treatment of nonconvulsive seizures in critically ill patients is uncertain. We evaluated the comparative effectiveness of the antiseizure drugs lacosamide (LCM) and fosphenytoin (fPHT) in this population. Methods: The TRENdS (Treatment of Recurrent Electrographic Nonconvulsive Seizures) study was a noninferiority, prospective, multicenter, randomized treatment trial of patients diagnosed with nonconvulsive seizures (NCSs) by continuous electroencephalography (cEEG). Treatment was randomized to intravenous (IV) LCM 400mg or IV fPHT 20mg phenytoin equivalents/kg. The primary endpoint was absence of electrographic seizures for 24 hours as determined by 1 blinded EEG reviewer. The frequency with which NCS control was achieved in each arm was compared, and the 90% confidence interval (CI) was determined. Noninferiority of LCM to fPHT was to be concluded if the lower bound of the CI for relative risk was >0.8. Results: Seventy-four subjects were enrolled (37 LCM, 37 fPHT) between August 21, 2012 and December 20, 2013. The mean age was 63.6 years; 38 were women. Seizures were controlled in 19 of 30 (63.3%) subjects in the LCM arm and 16 of 32 (50%) subjects in the fPHT arm. LCM was noninferior to fPHT (p = 0.02), with a risk ratio of 1.27 (90% CI = 0.88–1.83). Treatment emergent adverse events (TEAEs) were similar in both arms, occurring in 9 of 35 (25.7%) LCM and 9 of 37 (24.3%) fPHT subjects (p = 1.0). Interpretation: LCM was noninferior to fPHT in controlling NCS, and TEAEs were comparable. LCM can be considered an alternative to fPHT in the treatment of NCSs detected on cEEG.