UCB Pharma, Raleigh, NC, USA.
Epilepsia Open. 2021 Jun;6(2):359-368. doi: 10.1002/epi4.12482. Epub 2021 May 3.
Recently, a novel trial design has been proposed to overcome challenges with traditional placebo-controlled trials of antiepileptic drugs in infants and young children (≥1 month of age) (Auvin S, et al. Epilepsia Open 2019;4:537-43). The proposed time-to-event trial design involves seizure counting by caregivers and allows adjustment of the duration of the baseline period and duration of exposure to placebo or potentially ineffective treatment based on the patient's seizure burden and response. We performed post hoc analyses to mimic this trial design and evaluate its viability. As these analyses required trials with prolonged baseline and treatment periods and diary data, which is not a typical design of trials in infants and young children (1 month to <4 years of age), data from two trials in pediatric patients (4-16 years of age) were used.
We performed post hoc analyses of two randomized, double-blind, placebo-controlled trials of adjunctive levetiracetam (N159; NCT00615615) and lacosamide (SP0969; NCT01921205) in children and adolescents (4-16 years of age) with focal-onset seizures. In these analyses, patients were followed until they completed the 10-week maintenance period, discontinued during the maintenance period, or reached their "nth" seizure (n = number of seizures patient had during baseline). Efficacy was assessed by determining time to nth seizure.
In the analyses of both trials, patients on levetiracetam or lacosamide had a 34% lower risk of reaching their baseline seizure count during their 10-week maintenance period than patients on placebo. The previously published primary results of these trials also demonstrated efficacy of adjunctive levetiracetam and lacosamide.
Although these were post hoc analyses of trials in older children (4-16 years of age), our results provide supportive evidence for the utility of the novel time-to-event trial design for future trials in infants and young children (1 month to <4 years of age).
最近，提出了一种新的试验设计，以克服传统安慰剂对照试验在婴儿和幼儿（≥1 个月龄）中抗癫痫药物的挑战（Auvin S，等人。癫痫开放 2019；4：537-43）。所提出的时间事件试验设计涉及由护理人员进行的癫痫发作计数，并允许根据患者的癫痫发作负担和反应调整基线期和暴露于安慰剂或潜在无效治疗的持续时间。我们进行了事后分析以模拟该试验设计并评估其可行性。由于这些分析需要具有延长的基线和治疗期和日记数据的试验，这不是婴儿和幼儿（1 个月至<4 岁）试验的典型设计，因此使用了两项儿科患者（4-16 岁）的试验数据。
我们对两项随机、双盲、安慰剂对照的辅助左乙拉西坦（N159；NCT00615615）和拉考酰胺（SP0969；NCT01921205）临床试验进行了事后分析，这些试验纳入了伴有局灶性发作的儿童和青少年（4-16 岁）患者。在这些分析中，患者一直随访到完成 10 周的维持期，在维持期内停药或达到他们的“n 次”癫痫发作（n=患者在基线期间发生的癫痫发作次数）。通过确定达到 n 次癫痫发作的时间来评估疗效。
在两项试验的分析中，与安慰剂组相比，接受左乙拉西坦或拉考酰胺治疗的患者在 10 周维持期内达到基线癫痫发作次数的风险降低了 34%。这些试验的先前发表的主要结果也证明了辅助左乙拉西坦和拉考酰胺的疗效。
尽管这些是针对年龄较大的儿童（4-16 岁）的试验的事后分析，但我们的结果为在婴儿和幼儿（1 个月至<4 岁）中未来试验采用新型时间事件试验设计提供了支持性证据。
