title: Results of phase 2 safety and feasibility study of treatment with levetiracetam for prevention of posttraumatic epilepsy.
abstract: OBJECTIVE
  To evaluate the safety and tolerability of treatment with levetiracetam and determine the trough levels of levetiracetam in patients with traumatic brain injury (TBI) who are at high risk for posttraumatic epilepsy (PTE).
  
  
  METHODS
  Open-label, nonrandomized phase 2 study with 2 arms comparing levetiracetam treatment vs observation.
  
  
  METHODS
  Two level 1 trauma centers.
  
  
  METHODS
  A total of 422 participants 6 years or older with TBI who have a 20% risk for PTE were screened. Of these participants, 205 (48.6%) were eligible. A total of 126 participants were enrolled: 86 adults and 40 children. A total of 66 participants were in the treatment group (46 adults and 20 children), and a total of 60 participants were in the observation group (40 adults and 20 children). Participants presenting within 8 hours after TBI received treatment, and those presenting more than 8 to 24 hours after TBI did not.
  
  
  METHODS
  Treatment with levetiracetam (55 mg/kg/d) for 30 days starting within 8 hours after injury.
  
  
  METHODS
  Number of adverse events, mood score, number of infections, trough level of levetiracetam, and PTE.
  
  
  RESULTS
  Of the 66 participants treated with levetiracetam, 2 (3%) stopped treatment owing to toxicity (somnolence). The most common adverse events were fatigue, headache, and somnolence. Mood scores and number of infections did not differ between the treatment and observation groups. Mean trough levels of levetiracetam on days 2 to 30 ranged from 19.6 to 26.7 μg/mL. At 2 years, 13 of 86 adults (15.1%) and 1 of 40 children (2.5%) developed PTE. At 2 years, 5 of 46 treated adults (10.9%) and 8 of 40 untreated adults (20.0%) developed PTE (relative risk, 0.47; P=.18).
  
  
  CONCLUSIONS
  Treatment with 55 mg/kg/d of levetiracetam (a dose with an antiepileptogenic effect on animals) for patients with TBI at risk for PTE is safe and well tolerated, with plasma levels similar to those in animal studies. The findings support further evaluation of levetiracetam treatment for the prevention of PTE.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01463033.
authors: Department of Neurology, MedStar Research Institute, Washington, DC, USA. kleinp@epilepsydc.com
authors: Pavel
authors: P
authors: Klein
authors: Daniel
authors: D
authors: Herr
authors: Phillip L
authors: PL
authors: Pearl
authors: JoAnne
authors: J
authors: Natale
authors: Zachary
authors: Z
authors: Levine
authors: Claude
authors: C
authors: Nogay
authors: Fabian
authors: F
authors: Sandoval
authors: Stacey
authors: S
authors: Trzcinski
authors: Shireen M
authors: SM
authors: Atabaki
authors: Tammy
authors: T
authors: Tsuchida
authors: John
authors: J
authors: van den Anker
authors: Steven J
authors: SJ
authors: Soldin
authors: Jianping
authors: J
authors: He
authors: Robert
authors: R
authors: McCarter
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy; D002648:Child; D002851:Chromatography, High Pressure Liquid; D004827:Epilepsy / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D010672:Phenytoin / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D010889:Piracetam / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D016019:Survival Analysis; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D000077287:Levetiracetam; D010672:Phenytoin; D010889:Piracetam