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SANAD II

A study of Standard and New Antiepileptic Drugs – SANAD-II

SANAD II

A study of Standard and New Antiepileptic Drugs – SANAD-II
Funding NIHR - HTA
Portfolio Clinical Specialties
Interventions Medicine
Randomised Yes
Status Analysis/reporting
Start Date 01-Jan-0001

Epilepsy is a very common neurological condition and up to 3% of people will experience seizures at some time in their lives.
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.
Our previous trial (SANAD-I) compared the effectiveness and cost effectiveness of standard and new treatments that were available at that time. SANAD-I identified lamotrigine (a new drug) as an effective and cost-effective first-line treatment for patients with a focal epilepsy, and confirmed that valproate (a standard treatment) should remain a first-line drug for patients with a generalised epilepsy or seizures that clinicians find difficult to classify. Since SANAD-I, a number of newer treatments have become available, the most promising of which are levetiracetam and zonisamide. We now need to assess whether levetiracetam or zonisamide should become first-line treatments.
In SANAD-II, we propose to assess the longer term effectiveness and cost effectiveness of these drugs in two un-blinded randomised controlled trials run in parallel. The first (arm A) will compare lamotrigine, levetiracetam and zonisamide in patients with a focal epilepsy, and the second (arm B) will compare levetiracetam with valproate in patients with a generalized epilepsy or seizures that the clinician finds difficult to classify. SANAD-II will recruit 1510 patients (990 arm A, 520 arm B), aged 5 and over, starting treatment for epilepsy.

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Publications

  • Marson AG, Burnside G, Appleton R, et al. The SANAD II study of effectiveness of valproate or levetiracetam in generalised and unclassifiable epilepsy: an un-blinded randomised controlled trial. Presented at: International Epilepsy Conference; June 22-26; Bangkok, Thailand. Abstract: 1027.
  • Bonnett, L. J., Powell, G. A., Smith, C. T., & Marson, A. G. (2017). Breakthrough seizures-Further analysis of the Standard versus New Antiepileptic Drugs (SANAD) study. PLOS ONE, 12(12).
    1. https://doi.org/10.1371/journal.pone.0190035
  • Bonnett, L. J., Powell, G. A., Smith, C. T., & Marson, A. G. (2017). Risk of a seizure recurrence after a breakthrough seizure and the implications for driving: further analysis of the standard versus new antiepileptic drugs (SANAD) randomised controlled trial. BMJ OPEN, 7(7).
    1. https://doi.org/10.1136/bmjopen-2017-015868
  • Bonnett, L. J., Smith, C. T., Donegan, S., & Marson, A. G. (2014). Treatment outcome after failure of a first antiepileptic drug. NEUROLOGY, 83(6), 552-560.
    1. https://doi.org/10.1212/WNL.0000000000000673
  • Bonnett, L. J., Smith, C. T., Smith, D., Williamson, P. R., Chadwick, D., & Marson, A. G. (2014). Time to 12-month remission and treatment failure for generalised and unclassified epilepsy. JOURNAL OF NEUROLOGY NEUROSurgery AND PSYCHIATRY, 85(6), 603-610.
    1. https://doi.org/10.1136/jnnp-2013-306040
  • Chadwick, D. W., Marson, A. G., Tudur Smith, C., Jacoby, A., Gamble, C., Shackley, P., & Williamson, P. R. (2007). A Randomized Controlled Trial examining the Longer-term Outcomes of Established versus New Antiepileptic Drugs (SANAD). Health Technology Assessment monograph, 11(37).
  • Hickey G, Philipson P, Jorgensen A, Kolamunnage‐Dona R (2018). A comparison of different joint models for longitudinal and competing risks data: with application to an epilepsy drug randomised control trial. Journal of the Royal Statistical Society: Series A (Statistics in Society).
    1. https://doi.org/10.1111/rssa.12348
  • Hua, H., Burke, D. L., Crowther, M. J., Ensor, J., Tudur Smith, C., & Riley, R. D. (2017). One-stage individual participant data meta-analysis models: estimation of treatment-covariate interactions must avoid ecological bias by separating out within-trial and across-trial information. Statistics in medicine, 36(5), 772-789.
    1. https://doi.org/10.1002/sim.7171
  • Jacoby, A., Sudell, M., Smith, C. T., Crossley, J., Marson, A. G., Baker, G. A., & Grp, S. A. N. A. D. S. (2015). Quality-of-life outcomes of initiating treatment with standard and newer antiepileptic drugs in adults with new-onset epilepsy: Findings from the SANAD trial. EPILEPSIA, 56(3), 460-472.
    1. https://doi.org/10.1111/epi.12913
  • Kearney A, McKay A, Hickey H, Balabanova S, Marson, AG, Gamble C, Williamson PR. (2014) Opening research sites in multicentre clinical trials within the UK: A detailed analysis of delays. BMJ Open 4:e005874
    1. https://doi.org/10.1136/bmjopen-2014-005874
  • Marson AG, Al-Kharusi AM, Alwaidh M, Appleton R, Baker GA, Chadwick DW, Cramp C, Cockerell OC, Cooper PN, Doughty J, Eaton B , Gamble C, Goulding PJ, Howell SJL, Hughes A, Jackson M, Jacoby A, Kellett M, Lawson GR, Leach JP, Nicolaides P, Roberts R, Shackley P, Shen J, Smith DF, Smith PEM, Tudur Smith C, Vanoli A, Williamson PR on behalf of the SANAD Study group (2007). Carbamazepine, gabapentin, lamotrigine, oxcarbazepine or topiramate for partial epilepsy: results from the SANAD trial. Lancet 369:1000-1015
    1. https://doi.org/10.1016/S0140-6736(07)60460-7
  • Marson AG, Al-Kharusi AM, Alwaidh M, Appleton R, Baker GA, Chadwick DW, Cramp C, Cockerell OC, Cooper PN, Doughty J, Eaton B , Gamble C, Goulding PJ, Howell SJL, Hughes A, Jackson M, Jacoby A, Kellett M, Lawson GR, Leach JP, Nicolaides P, Roberts R, Shackley P, Shen J, Smith DF, Smith PEM, Tudur Smith C, Vanoli A, Williamson PR on behalf of the SANAD Study group (2007). Valproate, lamotrigine or topiramate for generalized and unclassifiable epilepsy: results from the SANAD trial. Lancet 369:1016-1026
    1. https://doi.org/10.1016/S0140-6736(07)60461-9
  • Marson AG, Tudur-Smith C, Gamble C, Shackley P, Williamson PR, Smith DF, Appleton R, Baker GA,Eaton B, Jacoby AJ, Chadwick DW. (2007) A randomised controlled trial examining the longer-term outcomes of standard versus new antiepileptic drugs. The SANAD trial. Health Technology Assessment 11 (37).
  • Nevitt, S. J., Sudell, M., Weston, J., Tudur Smith, C., & Marson, A. G. (2017). Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data. COCHRANE DATABASE OF SYSTEMATIC REVIEWS, (12).
    1. https://doi.org/10.1002/14651858.CD011412.pub3
  • Powell GA, Bonnett LJ, Tudur Smith C, Hughes DA, Williamson PR, Marson AG. (2017) Using Routinely Recorded Data in the UK to Assess Outcomes in a Randomised Controlled Trial: The Trials of Access. Trials 18:389.
    1. https://doi.org/10.1186/s13063-017-2135-9
  • Smith, C. T., Marson, A. G., Chadwick, D. W., & Williamson, P. R. (2007). Multiple treatment comparisons in epilepsy monotherapy trials. TRIALS, 8.
    1. https://doi.org/10.1186/1745-6215-8-34
  • Smith, C. T., Nevitt S, Appelbe D, Appleton R, Dixon P, Harrison J, Marson A, Williamson P, Tremain E. (2017). Resource implications of preparing individual participant data from a clinical trial to share with external researchers. TRIALS, 18.
    1. https://doi.org/10.1186/s13063-017-2067-4
  • Williamson PR, Kolamunnage-Dona R, Philipson P, Marson AG. (2008). Joint modelling of longitudinal and competing risks data. Statistics in Medicine 27: 6426-6438.