Electronic versions



  • Silviya Balabanova
    Alder Hey Children's NHS Foundation Trust
  • Claire Taylor
    Alder Hey Children's NHS Foundation Trust
  • Graeme Sills
    University of Glasgow
  • Girvan Burnside
    University of Liverpool
  • Catrin Plumpton
  • Phil Smith
    University Hospital of Wales
  • Richard Appleton
    Alder Hey Children's NHS Foundation Trust
  • John Paul Leach
    University of Glasgow
  • Michael Johnson
    University of Glasgow
  • Gus A. Baker
    University of Liverpool
  • Munir Pirmohamed
    University of Liverpool
  • Dyfrig Hughes
  • Paula Williamson
    University of Liverpool
  • Catrin Tudor-Smith
    University of Liverpool
  • Anthony G. Marson
    University of Liverpool
Introduction: Antiepileptic drugs (AEDs) are the mainstay of epilepsy treatment. Over the past 20 years, a number of new drugs have been approved for NHS use on the basis of information from short term trials that demonstrate efficacy. These trials do not provide information about the longer term outcomes, which inform treatment policy. This trial will assess the long term clinical and cost-effectiveness of the newer treatments levetiracetam and zonisamide.
Methods and analysis: This is a phase IV, multicentre, open-label, randomised, controlled clinical trial comparing new and standard treatments for patients with newly-diagnosed epilepsy. Arm A of the trial randomised 990 patients with focal epilepsy to standard AED lamotrigine or new AEDs levetiracetam or zonisamide. Arm B randomised 520 patients with generalised epilepsy to standard AED sodium valproate or new AED levetiracetam. Patients are recruited from United Kingdom NHS out-patient epilepsy, general neurology and paediatric clinics. Included patients are aged 5 years or older with two or more spontaneous seizures requiring AED monotherapy, who are not previously treated with AEDs. Patients are followed-up for a minimum of 2 years. The primary outcome is time to 12-month remission from seizures. Secondary outcomes include time to treatment failure (including due to inadequate seizure control or due to unacceptable adverse reactions); time to first seizure; time to 24-month remission; adverse reactions and quality of life. All primary analyses will be on an intention to treat basis. Separate analyses will be undertaken for each arm. Health economic analysis will be conducted from the perspective of the NHS to assess the cost-effectiveness of each AED.


  • clinical trials, epilepsy, health economics, health policy, paediatric neurology
Original languageEnglish
Article numbere040635
JournalBMJ Open
Issue number8
Publication statusPublished - 26 Aug 2020

Total downloads

No data available
View graph of relations