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Prospective, Randomized, Single-Blinded Comparative Trial of Intravenous Levetiracetam Versus Phenytoin for Seizure Prophylaxis

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Abstract

Background

Anti-epileptic drugs are commonly used for seizure prophylaxis after neurological injury. We performed a study comparing intravenous (IV) levetiracetam (LEV) to IV phenytoin (PHT) for seizure prophylaxis after neurological injury.

Methods

In this prospective, single-center, randomized, single-blinded comparative trial of LEV versus PHT (2:1 ratio) in patients with severe traumatic brain injury (sTBI) or subarachnoid hemorrhage (NCT00618436) patients received IV load with either LEV or fosphenytoin followed by standard IV doses of LEV or PHT. Doses were adjusted to maintain therapeutic serum PHT concentrations or if patients had seizures. Continuous EEG (cEEG) monitoring was performed for the initial 72 h; outcome data were collected.

Results

A total of 52 patients were randomized (LEV = 34; PHT = 18); 89% with sTBI. When controlling for baseline severity, LEV patients experienced better long-term outcomes than those on PHT; the Disability Rating Scale score was lower at 3 months (P = 0.042) and the Glasgow Outcomes Scale score was higher at 6 months (P = 0.039). There were no differences between groups in seizure occurrence during cEEG (LEV 5/34 vs. PHT 3/18; P = 1.0) or at 6 months (LEV 1/20 vs. PHT 0/14; P = 1.0), mortality (LEV 14/34 vs. PHT 4/18; P = 0.227). There were no differences in side effects between groups (all P > 0.15) except for a lower frequency of worsened neurological status (P = 0.024), and gastrointestinal problems (P = 0.043) in LEV-treated patients.

Conclusions

This study of LEV versus PHT for seizure prevention in the NSICU showed improved long-term outcomes of LEV-treated patients vis-à-vis PHT-treated patients. LEV appears to be an alternative to PHT for seizure prophylaxis in this setting.

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Acknowledgments

This study was supported by a grant from UCB Inc., Principal Investigator: Lori A. Shutter, MD. This study was presented in part at the Neurocritical Care Society Meetings in 2008 and 2009. Data Safety Monitoring Board included Drs. Andrew Ringer, MD (Department of Neurosurgery) and Michael D. Privitera, MD (Department of Neurology).

Disclosure of Conflicts of Interest

Jerzy P. Szaflarski, MD, PhD has received grant support from the American Academy of Neurology, Davis Phinney Foundation/Sunflower Revolution, National Institutes of Health, UCB Pharma Inc., and The University Research Council at the University of Cincinnati. He has served as a paid consultant and/or speaker for Abbott Laboratories, American Academy of Neurology, Pfizer and UCB, Inc. Kiranpal S. Sangha, Pharm.D—has nothing to disclose. Christopher J. Lindsell, PhD—has received grant support from Abbott POC. Lori A. Shutter, MD has received grant support for the Department of Defense, National Institute of Health, and UCB Pharma, Inc. She has served as a paid consultant and/or speaker for Integra Lifesciences and the Brain Trauma Foundation.

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Authors and Affiliations

  1. Department of Neurology, University of Cincinnati Academic Health Center, 260 Stetson Street, Rm. 2350, Cincinnati, OH, 45267-0525, USA

    Jerzy P. Szaflarski & Lori A. Shutter

  2. Cincinnati Epilepsy Center at the University Hospital, Cincinnati, OH, USA

    Jerzy P. Szaflarski

  3. The University of Cincinnati Neuroscience Institute, Cincinnati, OH, USA

    Jerzy P. Szaflarski & Lori A. Shutter

  4. Department of Pharmacy Services, The University Hospital, Cincinnati, OH, USA

    Kiranpal S. Sangha

  5. James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH, USA

    Kiranpal S. Sangha

  6. Department of Emergency Medicine, University of Cincinnati Academic Health Center, Cincinnati, OH, USA

    Christopher J. Lindsell

  7. Department of Neurosurgery, University of Cincinnati Academic Health Center, Cincinnati, OH, USA

    Lori A. Shutter

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  1. Jerzy P. Szaflarski
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  2. Kiranpal S. Sangha
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  3. Christopher J. Lindsell
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  4. Lori A. Shutter
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Correspondence to Jerzy P. Szaflarski.

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Szaflarski, J.P., Sangha, K.S., Lindsell, C.J. et al. Prospective, Randomized, Single-Blinded Comparative Trial of Intravenous Levetiracetam Versus Phenytoin for Seizure Prophylaxis. Neurocrit Care 12, 165–172 (2010). https://doi.org/10.1007/s12028-009-9304-y

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  • DOI: https://doi.org/10.1007/s12028-009-9304-y

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