Study protocol for a pragmatic randomised controlled trial comparing the effectiveness and cost-effectiveness of levetiracetam and zonisamide versus standard treatments for epilepsy: a comparison of standard and new antiepileptic drugs (SANAD-II)
Introduction Antiepileptic drugs (AEDs) are the mainstay of epilepsy treatment. Over the past 20 years, a number of new drugs have been approved for National Health Service (NHS) use on the basis of information from short-term trials that demonstrate efficacy. These trials do not provide information...
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BMJ Publishing Group
2020-08-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/10/8/e040635.full |
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| author | Girvan Burnside Munir Pirmohamed Dyfrig A Hughes Paula R Williamson Anthony Guy Marson Claire Taylor Phil E M Smith John Paul Leach Gus Baker Catrin Tudur-Smith Richard Appleton Michael Johnson Silviya Balabanova Graeme Sills Catrin Plumpton |
| author_facet | Girvan Burnside Munir Pirmohamed Dyfrig A Hughes Paula R Williamson Anthony Guy Marson Claire Taylor Phil E M Smith John Paul Leach Gus Baker Catrin Tudur-Smith Richard Appleton Michael Johnson Silviya Balabanova Graeme Sills Catrin Plumpton |
| author_sort | Girvan Burnside |
| collection | DOAJ |
| description | Introduction Antiepileptic drugs (AEDs) are the mainstay of epilepsy treatment. Over the past 20 years, a number of new drugs have been approved for National Health Service (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 treatment 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 AED levetiracetam or zonisamide. Arm B randomised 520 patients with generalised epilepsy to standard AED sodium valproate or new AED levetiracetam. Patients are recruited from UK NHS outpatient 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 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.Ethics and dissemination This trial has been approved by the North West-Liverpool East REC (Ref. 12/NW/0361). The trial team will disseminate the results through scientific meetings, peer-reviewed publications and patient and public involvement.Trial registration numbers EudraCT 2012-001884-64; ISRCTN30294119. |
| format | Article |
| id | doaj-art-541ff5dc48e5411788ae6c76f19c71fa |
| institution | OA Journals |
| issn | 2044-6055 |
| language | English |
| publishDate | 2020-08-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-541ff5dc48e5411788ae6c76f19c71fa2025-08-20T02:38:42ZengBMJ Publishing GroupBMJ Open2044-60552020-08-0110810.1136/bmjopen-2020-040635Study protocol for a pragmatic randomised controlled trial comparing the effectiveness and cost-effectiveness of levetiracetam and zonisamide versus standard treatments for epilepsy: a comparison of standard and new antiepileptic drugs (SANAD-II)Girvan Burnside0Munir Pirmohamed1Dyfrig A Hughes2Paula R Williamson3Anthony Guy Marson4Claire Taylor5Phil E M Smith6John Paul Leach7Gus Baker8Catrin Tudur-Smith9Richard Appleton10Michael Johnson11Silviya Balabanova12Graeme Sills13Catrin Plumpton14Department of Biostatistics, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, Liverpool, UKMRC Centre for Drug Safety Science and Wolfson Centre for Personalised Medicine, Institute of Systems, Molecular and Integrative Biology (ISMIB), University of Liverpool, Liverpool, UKCentre for Health Economics & Medicines Evaluation, Bangor University, Bangor, UKDepartment of Biostatistics, University of Liverpool, Liverpool, UK3 Department of Neurology, The Walton Centre NHS Foundation Trust, Liverpool, UKLiverpool Clinical Trials Centre, University of Liverpool, Liverpool, UKUniversity Hospital of Wales, Cardiff, UK7 School of Medicine, University of Glasgow, Glasgow, UK9 Molecular and Clinical Pharmacology, University of Liverpool, Faculty of Health and Life Sciences, Liverpool, UKDepartment of Biostatistics, University of Liverpool, Liverpool, UK2 Paediatric neurology, Alder Hey Children`s NHS Foundation Trust, Liverpool, Merseyside, UKEli Lilly and Company, Indianapolis, United States of America1 Liverpool Clinical Trials Centre, University of Liverpool, Faculty of Health and Life Sciences, Liverpool, UK2 School of Life Sciences, University of Glasgow, Glasgow, UK4 Centre for Health Economics and Medicines Evaluation, Bangor University, Bangor, UKIntroduction Antiepileptic drugs (AEDs) are the mainstay of epilepsy treatment. Over the past 20 years, a number of new drugs have been approved for National Health Service (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 treatment 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 AED levetiracetam or zonisamide. Arm B randomised 520 patients with generalised epilepsy to standard AED sodium valproate or new AED levetiracetam. Patients are recruited from UK NHS outpatient 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 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.Ethics and dissemination This trial has been approved by the North West-Liverpool East REC (Ref. 12/NW/0361). The trial team will disseminate the results through scientific meetings, peer-reviewed publications and patient and public involvement.Trial registration numbers EudraCT 2012-001884-64; ISRCTN30294119.https://bmjopen.bmj.com/content/10/8/e040635.full |
| spellingShingle | Girvan Burnside Munir Pirmohamed Dyfrig A Hughes Paula R Williamson Anthony Guy Marson Claire Taylor Phil E M Smith John Paul Leach Gus Baker Catrin Tudur-Smith Richard Appleton Michael Johnson Silviya Balabanova Graeme Sills Catrin Plumpton Study protocol for a pragmatic randomised controlled trial comparing the effectiveness and cost-effectiveness of levetiracetam and zonisamide versus standard treatments for epilepsy: a comparison of standard and new antiepileptic drugs (SANAD-II) BMJ Open |
| title | Study protocol for a pragmatic randomised controlled trial comparing the effectiveness and cost-effectiveness of levetiracetam and zonisamide versus standard treatments for epilepsy: a comparison of standard and new antiepileptic drugs (SANAD-II) |
| title_full | Study protocol for a pragmatic randomised controlled trial comparing the effectiveness and cost-effectiveness of levetiracetam and zonisamide versus standard treatments for epilepsy: a comparison of standard and new antiepileptic drugs (SANAD-II) |
| title_fullStr | Study protocol for a pragmatic randomised controlled trial comparing the effectiveness and cost-effectiveness of levetiracetam and zonisamide versus standard treatments for epilepsy: a comparison of standard and new antiepileptic drugs (SANAD-II) |
| title_full_unstemmed | Study protocol for a pragmatic randomised controlled trial comparing the effectiveness and cost-effectiveness of levetiracetam and zonisamide versus standard treatments for epilepsy: a comparison of standard and new antiepileptic drugs (SANAD-II) |
| title_short | Study protocol for a pragmatic randomised controlled trial comparing the effectiveness and cost-effectiveness of levetiracetam and zonisamide versus standard treatments for epilepsy: a comparison of standard and new antiepileptic drugs (SANAD-II) |
| title_sort | study protocol for a pragmatic randomised controlled trial comparing the effectiveness and cost effectiveness of levetiracetam and zonisamide versus standard treatments for epilepsy a comparison of standard and new antiepileptic drugs sanad ii |
| url | https://bmjopen.bmj.com/content/10/8/e040635.full |
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