Randomized trial of lacosamide versus fosphenytoin for nonconvulsive seizures.

Authors:
Aatif M Husain
Aatif M Husain
Duke University Medical Center
United States
Jong W Lee
Jong W Lee
College of Medicine
Bradley J Kolls
Bradley J Kolls
University of California
Lawrence J Hirsch
Lawrence J Hirsch
Comprehensive Epilepsy Center
Jonathan J Halford
Jonathan J Halford
Medical University of South Carolina
Puneet K Gupta
Puneet K Gupta
University of Texas Southwestern Medical Center
United States
Jennifer M Jones
Jennifer M Jones
Princess Margaret Hospital
Toronto | Canada

Ann Neurol 2018 Jun;83(6):1174-1185

Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.

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.

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Source
http://doi.wiley.com/10.1002/ana.25249
Publisher Site
http://dx.doi.org/10.1002/ana.25249DOI Listing
June 2018
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