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Research paper
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
  1. Eugen Trinka1,
  2. Anthony G Marson2,
  3. Wim Van Paesschen3,
  4. Reetta Kälviäinen4,
  5. Jacqueline Marovac5,
  6. Benjamin Duncan6,
  7. Sonja Buyle5,
  8. Yngve Hallström7,
  9. Petr Hon8,
  10. Gian Carlo Muscas9,
  11. Mark Newton10,
  12. Heinz-Joachim Meencke11,
  13. Philip E Smith12,
  14. Bernd Pohlmann-Eden13,
  15. for the KOMET Study Group
  1. 1Department of Neurology, Paracelsus Medical University, Christian Doppler Klinik, Salzburg, Austria
  2. 2Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK
  3. 3Department of Neurology, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium
  4. 4Department of Neurology, Kuopio Epilepsy Center, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland
  5. 5UCB Pharma, Brussels, Belgium
  6. 6UCB Pharma, Raleigh, North Carolina, USA
  7. 7Neuro Center, St Goran's Hospital, Stockholm, Sweden
  8. 8Department of Neurology, University Hospital Ostrava, Ostrava, Czech Republic
  9. 9Department of Neuroscience, 3rd Neurology Division and Epilepsy Center, Careggi Hospital, Florence, Italy
  10. 10Epilepsy Research Centre Heidelberg West, Melbourne, Australia
  11. 11Department of Epileptology, Hospital Königin Elisabeth Herzberge, Berlin, Germany
  12. 12Wales Epilepsy Research Network, University Hospital of Wales, Cardiff, UK
  13. 13Epilepsy Program, QE II Health Centre, Dalhousie University, Halifax, Canada
  1. Correspondence to Dr Eugen Trinka, Department of Neurology, Paracelsus Medical University, Christian Doppler Klinik, Ignaz Harrer Strasse 79, A-5020 Salzburg, Austria; e.trinka{at}salk.at

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.

Findings 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.

  • Levetiracetam
  • valproic acid
  • carbamazepine
  • epilepsy
  • monotherapy
  • neurophysiol
  • clinical
  • neuroepidemiology
  • surgery
  • MRI

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Footnotes

  • GCM is deceased.

  • Funding KOMET was funded and sponsored by UCB Pharma who was responsible for the design and conduct of the study, and collection, management, analysis and interpretation of the data. Medical writing and editorial assistance was provided by Jennifer Stewart, MSc, (QXV Communications, Macclesfield, UK), and was funded by UCB Pharma.

  • Competing interests ET has acted as a paid consultant to Eisai, Medtronics, Bial and UCB Pharma. He has received research funding from UCB Pharma, and speakers' honoraria from Bial, Cyberonics, Desitin Pharma, Eisai, Gerot and UCB Pharma. AGM has received research funding from UCB Pharma, Eisai, GlaxoSmithKline (GSK) and Pfizer, has acted as a paid consultant to UCB Pharma and Cyberonics and has received speakers' honoraria from Sanofi-Aventis and GSK, and travel grants from GSK, UCB Pharma, Janssen-Cilag, Eisai and Sanofi-Aventis. WVP has acted as a paid consultant to and has received speakers' honoraria from UCB Pharma, Pfizer, Janssen-Cilag, Valeant, Johnson & Johnson (J&J), Eisai, Sanofi-Aventis, Novartis and GSK. He has received research funding from UCB Pharma, and travel grants from UCB Pharma, Pfizer, GSK, Janssen-Cilag and Novartis. RK has acted as a board member for UCB Pharma and Eisai, and as a paid consultant to UCB Pharma, Eisai, Orion Pharma and Janssen-Cilag, and has received research grants from UCB Pharma, speakers' honoraria from UCB Pharma, Eisai, Pfizer, Orion Pharma, Sanofi-Aventis and Janssen-Cilag, and travel grants from UCB Pharma, Eisai, Pfizer, Orion Pharma, Sanofi-Aventis, Cephalon and J&J. JM and SB were full-time employees of UCB Pharma at the time when the KOMET study was conducted and the results analysed. BD is a full-time employee of UCB Pharma. YH has been a paid advisory board member to UCB Pharma and Pfizer. PH has no relevant financial relationships outside the submitted work. GCM (deceased) had received speakers' or consultancy fees and/or travel/accommodation grants for participation in medical congresses and investigators' meetings from Cyberonics, Eisai, Eli Lilly, Novartis, Pfizer, Sanofi-Aventis and UCB Pharma. MN has received a speakers' honorarium from UCB Pharma. H-JM was a paid consultant to UCB Pharma and Eisai. He has received unrestricted research grants from Janssen-Cilag, Pfizer, and UCB Pharma and speakers' honoraria from Cyberonics, Desitin Pharma, Eisai, Novartis, Janssen-Cilag, Pfizer, and UCB Pharma. PS has received an unrestricted research grant from UCB Pharma, speakers' honoraria from UCB Pharma and Eisai, and travel grants from UCB Pharma and Janssen-Cilag. B P-E was a paid consultant to Desitin Pharma, UCB Pharma, Janssen-Cilag and Pfizer. He received research and trial grants from UCB Pharma and Pfizer, and speakers' honoraria from UCB Pharma, Pfizer, Desitin Pharma, Eisai and Janssen-Cilag.

  • Ethics approval The study was approved by the local ethics committees for every study centre.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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