The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial.
The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial.
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DOI：
10.1016/s0140-6736(07)60460-7
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发表时间：
2007-03-24
期刊：
影响因子：
168.9
通讯作者：
Williamson, Paula R.
中科院分区：
文献类型：
--
作者：
Marson, Anthony G.;Al-Kharusi, Asya M.;Alwaidh, Muna;Appleton, Richard;Baker, Gus A.;Chadwick, David W.;Cramp, Celia;Cockerell, Oliver C.;Cooper, Paul N.;Doughty, Julie;Eaton, Barbara;Gamble, Carrot;Goulding, Peter J.;Howell, Stephen J. L.;Hughes, Adrian;Jackson, Margaret;Jacoby, Ann;Kellett, Mark;Lawson, Geoffrey R.;Leach, John Paul;Nicolaides, Paola;Roberts, Richard;Shackley, Phil;Shen, Jing;Smith, David F.;Smith, Philip E. M.;Smith, Catrin Tudur;Vanoli, Alessandra;Williamson, Paula R.
卡马西平被广泛接受为癫痫部分发作患者的首选药物。几种新药对这些癫痫发作类型具有疗效，但以前的随机对照试验未能告知这些药物之间的选择。我们的目的是评估长期结果、生活质量和健康经济结果的有效性。SANAD是一项在英国医院门诊进行的非盲随机对照试验。A组招募了1721例卡马西平被认为是标准治疗的患者，他们被随机分配接受卡马西平，加巴喷丁，拉莫三嗪，奥卡西平或托吡酯。主要结局为至治疗失败的时间和至12个月缓解的时间，并通过意向治疗和符合方案进行评估。本研究注册为国际标准随机对照试验，编号ISRCTN 38354748。对于至治疗失败的时间，拉莫三嗪显著优于卡马西平（风险比[HR] 0.78 [95% CI 0.63 - 0.97]）、加巴喷丁（0.65 [0.52 - 0.80]）和托吡酯（0.64 [0.52 - 0.79]），与奥卡西平相比无显著优势（1.15 [0.86 - 1.54]）。对于12个月缓解时间，卡马西平显著优于加巴喷丁（0.75 [0.63 - 0.90]），估计表明卡马西平与拉莫三嗪（0.91 [0.77 - 1.09]）、托吡酯（0.86 [0.72 - 1.03]）和奥卡西平（0.92 [0.73 - 1.18]）相比无显著优势。在符合方案分析中，在2年和4年时，达到12个月缓解（拉莫三嗪-卡马西平）的比例差异（95% CI）为0（−8至7）和5（−3至12），表明拉莫三嗪与卡马西平相比具有非劣效性。拉莫三嗪在临床上优于标准药物治疗卡马西平，治疗失败的时间结果，因此是诊断为部分性发作癫痫患者的一种具有成本效益的替代方案。
Carbamazepine is widely accepted as a drug of first choice for patients with partial onset seizures. Several newer drugs possess efficacy against these seizure types but previous randomised controlled trials have failed to inform a choice between these drugs. We aimed to assess efficacy with regards to longer-term outcomes, quality of life, and health economic outcomes. SANAD was an unblinded randomised controlled trial in hospital-based outpatient clinics in the UK. Arm A recruited 1721 patients for whom carbamazepine was deemed to be standard treatment, and they were randomly assigned to receive carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate. Primary outcomes were time to treatment failure, and time to 12-months remission, and assessment was by both intention to treat and per protocol. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN38354748. For time to treatment failure, lamotrigine was significantly better than carbamazepine (hazard ratio [HR] 0·78 [95% CI 0·63–0·97]), gabapentin (0·65 [0·52–0·80]), and topiramate (0·64 [0·52–0·79]), and had a non-significant advantage compared with oxcarbazepine (1·15 [0·86–1·54]). For time to 12-month remission carbamazepine was significantly better than gabapentin (0·75 [0·63–0·90]), and estimates suggest a non-significant advantage for carbamazepine against lamotrigine (0·91 [0·77–1·09]), topiramate (0·86 [0·72–1·03]), and oxcarbazepine (0·92 [0·73–1·18]). In a per-protocol analysis, at 2 and 4 years the difference (95% CI) in the proportion achieving a 12-month remission (lamotrigine-carbamazepine) is 0 (−8 to 7) and 5 (−3 to 12), suggesting non-inferiority of lamotrigine compared with carbamazepine. Lamotrigine is clinically better than carbamazepine, the standard drug treatment, for time to treatment failure outcomes and is therefore a cost-effective alternative for patients diagnosed with partial onset seizures.