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Randomized trial of lacosamide versus fosphenytoin for nonconvulsive seizures
Author(s) -
Husain Aatif M.,
Lee Jong W.,
Kolls Bradley J.,
Hirsch Lawrence J.,
Halford Jonathan J.,
Gupta Puneet K.,
Minazad Yafa,
Jones Jennifer M.,
LaRoche Suzette M.,
Herman Susan T.,
Swisher Christa B.,
Sinha Saurabh R.,
Palade Adriana,
Dombrowski Keith E.,
Gallentine William B.,
Hahn Cecil D.,
Gerard Elizabeth E.,
Bhapkar Manjushri,
Lokhnygina Yuliya,
Westover M. Brandon
Publication year - 2018
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.25249
Subject(s) - lacosamide , medicine , confidence interval , adverse effect , anesthesia , randomized controlled trial , clinical endpoint , electroencephalography , phenytoin , population , epilepsy , psychiatry , environmental health
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. Ann Neurol 2018;83:1174–1185