Title: 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)
Funder: Department of Health and Social Care

Abstract: Epilepsy is a common neurological condition. It is uniquely stigmatising and has a negative impact on quality of life and employment prospects. Antiepileptic drugs are the mainstay of treatment and may have to be taken for life. The ultimate goal of treatment is to maximise quality of life by eliminating seizures at drug doses that do not cause side effects. However, for many patients there is a necessary trade off between effective seizure control and side effects, which can diminish quality of life. Over the past 20 years, a number of new AED drugs have become available and have been approved for NHS use on the basis of information from short term trials. These trials do not provide information about the longer term outcomes which inform decisions made by doctors and patients, nor do they provide any useful health economic data. SANADII is a phase IV multicentre pragmatic randomised controlled trial comparing the effectiveness and cost-effectiveness of levetiracetam and zonisamide versus standard treatments (lamotrigine and valproate) for epilepsy. SANADII is essentially two randomised controlled trials run in parallel. Arm A of SANADII is comparing lamotrigine, levetiracetam and zonisamide in patients with untreated focal onset seizures. Arm B of SANADII is comparing levetiracetam and valproate in patients with generalised onset seizures or seizures that are difficult to classify. SANADII aims to accrue about 1510 patients (children aged 5 or older and adults) over a 3.5 year period and follow up will continue for a further two years (a maximum time a patient will receive randomised treatment is 5.5 years). Arm B closed to recruitment in August 2016 after reaching its recruitment target. Arm A, however, will continue recruiting for an additional year (until end of May 2017) in order to reach its recruitment target. There will be economy of scale given that the protocols and data structure are almost identical and that the same group of collaborators will be recruiting patients to both trials. There will be no competition for patients between Arm A and Arm B as the inclusion criteria are mutually exclusive. All treatments will be prescribed and issued as per routine NHS practice.

Lay abstract: Epilepsy is a common neurological (brain) disorder. Approximately 2-3% of the population will be given a diagnosis of epilepsy by the time they reach 60. A number of new drugs have been approved to treat epilepsy in the United Kingdom in the past few years. These drugs have been shown in research studies to prevent seizures and to be safe. There is as yet, however, no good evidence as to whether they are better at treating epileptic seizures or safer than the standard drugs that have been used for many years. SANADII will compare the standard and new antiepileptic drugs to identify which drugs are the most effective and which ones make the best use of NHS resources. SANADII started in 2012. Patients diagnosed as having a localised or focal epilepsy will receive treatment with either the standard treatment drug, lamotrigine, or the new treatment drugs, levetiracetam or zonisamide. Patients diagnosed as having a generalized or unclassified epilepsy will receive treatment with the standard treatment drug, valproate, or the new treatment drug, levetiracetam. After treatment has been started patients will be followed up in clinic, typically at 3, 6 and 12 monthly intervals, as is usual in the NHS, and annually thereafter, depending on how well they feel. Also, patients will be asked to keep seizures diary and to complete some questionnaires. SANADII will recruit over 1,500 patients with epilepsy (children aged 5 or older and adults) and will aim to follow up everyone until 2019. The results of SANADII study may help us to improve the treatment of epilepsy in the future.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: NEUROLOGICAL