title: KOMET: an unblinded, randomised, two parallel-group, stratified trial comparing the effectiveness of levetiracetam with controlled-release carbamazepine and extended-release sodium valproate as monotherapy in patients with newly diagnosed epilepsy.
abstract: OBJECTIVE
  To compare the effectiveness of levetiracetam (LEV) with extended-release sodium valproate (VPA-ER) and controlled-release carbamazepine (CBZ-CR) as monotherapy in patients with newly diagnosed epilepsy.
  
  
  METHODS
  This unblinded, randomised, 52-week superiority trial (NCT00175903) recruited patients (≥16 years of age) with ≥2 unprovoked seizures in the previous 2 years and ≥1 in the previous 6 months. The physician chose VPA or CBZ as preferred standard treatment; each patient was randomised to standard treatment or LEV. The primary outcome was time to treatment withdrawal (LEV vs standard antiepileptic drugs (AEDs)). Analyses also compared LEV with VPA-ER, and LEV with CBZ-CR.
  
  
  RESULTS
  1688 patients (mean age 41 years; 44% female) were randomised to LEV (n=841) or standard AEDs (n=847). Time to treatment withdrawal was not significantly different between LEV and standard AEDs: HR (95% CI) 0.90 (0.74 to 1.08). Time to treatment withdrawal (HR (95% CI)) was 1.02 (0.74 to 1.41) for LEV/VPA-ER and 0.84 (0.66 to 1.07) for LEV/CBZ-CR. Time to first seizure (HR, 95% CI) was significantly longer for standard AEDs, 1.20 (1.03 to 1.39), being 1.19 (0.93 to 1.54) for LEV/VPA-ER and 1.20 (0.99 to 1.46) for LEV/CBZ-CR. Estimated 12-month seizure freedom rates from randomisation: 58.7% LEV versus 64.5% VPA-ER; 50.5% LEV versus 56.7% CBZ-CR. Similar proportions of patients within each stratum reported at least one adverse event: 66.1% LEV versus 62.0% VPA-ER; 73.4% LEV versus 72.5% CBZ-CR.
  
  
  CONCLUSIONS
  LEV monotherapy was not superior to standard AEDs for the global outcome, namely time to treatment withdrawal, in patients with newly diagnosed focal or generalised seizures.
authors.affiliation: Department of Neurology, Paracelsus Medical University, Christian Doppler Klinik, Salzburg, Austria. e.trinka@salk.at
authors.forename: Eugen
authors.initials: E
authors.lastname: Trinka
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Marson
authors.forename: Wim
authors.initials: W
authors.lastname: Van Paesschen
authors.forename: Reetta
authors.initials: R
authors.lastname: Kälviäinen
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Marovac
authors.forename: Benjamin
authors.initials: B
authors.lastname: Duncan
authors.forename: Sonja
authors.initials: S
authors.lastname: Buyle
authors.forename: Yngve
authors.initials: Y
authors.lastname: Hallström
authors.forename: Petr
authors.initials: P
authors.lastname: Hon
authors.forename: Gian Carlo
authors.initials: GC
authors.lastname: Muscas
authors.forename: Mark
authors.initials: M
authors.lastname: Newton
authors.forename: Heinz-Joachim
authors.initials: HJ
authors.lastname: Meencke
authors.forename: Philip E
authors.initials: PE
authors.lastname: Smith
authors.forename: Bernd
authors.initials: B
authors.lastname: Pohlmann-Eden
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D002220:Carbamazepine / Q000009:adverse effects / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004569:Electroencephalography / Q000187:drug effects; D004828:Epilepsies, Partial / Q000175:diagnosis / Q000188:drug therapy*; D004829:Epilepsy, Generalized / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D000077287:Levetiracetam; D008297:Male; D008875:Middle Aged; D010352:Patient Dropouts; D010889:Piracetam / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011788:Quality of Life; D012815:Signal Processing, Computer-Assisted; D014635:Valproic Acid / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D003692:Delayed-Action Preparations; D002220:Carbamazepine; D000077287:Levetiracetam; D014635:Valproic Acid; D010889:Piracetam