TY - JOUR

T1 - 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)

AU - Balabanova, Silviya

AU - Taylor, Claire

AU - Sills, Graeme

AU - Burnside, Girvan

AU - Plumpton, Catrin

AU - Smith, Phil

AU - Appleton, Richard

AU - Leach, John Paul

AU - Johnson, Michael

AU - Baker, Gus A.

AU - Pirmohamed, Munir

AU - Hughes, Dyfrig

AU - Williamson, Paula

AU - Tudor-Smith, Catrin

AU - Marson, Anthony G.

N1 - © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.

PY - 2020/8/26

Y1 - 2020/8/26

N2 - 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.

AB - 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.

KW - clinical trials

KW - epilepsy

KW - health economics

KW - health policy

KW - paediatric neurology

U2 - https://doi.org/10.1136/bmjopen-2020-040635

DO - https://doi.org/10.1136/bmjopen-2020-040635

M3 - Article

C2 - 32847927

VL - 10

JO - BMJ Open

JF - BMJ Open

SN - 2044-6055

IS - 8

M1 - e040635

ER -