A Proof-of-Concept Study on Effectiveness of Nitrazepam in Resistant Infantile Epileptic Spasms Syndrome (NitRIS Trial)

IF 2.1 3区医学 Q2 CLINICAL NEUROLOGY

Pediatric neurology Pub Date : 2025-09-08 DOI:10.1016/j.pediatrneurol.2025.09.001

Parth Lal MBBS , Sandeep Negi PhD , Kiran Prakash MD , Dipika Bansal DM , Naveen Sankhyan DM , Jitendra Kumar Sahu DM

{"title":"A Proof-of-Concept Study on Effectiveness of Nitrazepam in Resistant Infantile Epileptic Spasms Syndrome (NitRIS Trial)","authors":"Parth Lal MBBS , Sandeep Negi PhD , Kiran Prakash MD , Dipika Bansal DM , Naveen Sankhyan DM , Jitendra Kumar Sahu DM","doi":"10.1016/j.pediatrneurol.2025.09.001","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Globally, pediatric neurologists vary in their choice of antiseizure medications for children with infantile epileptic spasms syndrome (IESS) who are resistant to hormonal and vigabatrin therapy. This trial aimed to determine whether oral nitrazepam is more effective than oral topiramate in achieving complete cessation of epileptic spasms (ES) in such cases.</div></div><div><h3>Methods</h3><div>We conducted an open-label, randomized controlled trial with a superiority hypothesis and masked end point assessments. The primary effectiveness end point was complete and sustained cessation of ES for 4 weeks, assessed at 10 weeks post-randomization. Secondary end points included electroclinical remission, time to remission, quality of life (assessed using the Hindi version of the Quality of Life of the Infant scale), autonomic tone (measured via heart rate variability), and adverse events.</div></div><div><h3>Results</h3><div>Between June 2023 and December 2024, 80 children with resistant IESS were screened and 40 (29 boys, 11 girls) were randomized to receive oral nitrazepam (0.5-3 mg/kg/day; n = 20) or topiramate (2-12 mg/kg/day; n = 20). Complete cessation of ES was achieved in 55% with nitrazepam vs 15% with topiramate (<em>P</em> = 0.019) and electroclinical remission in 45% vs 10% (<em>P</em> = 0.031). Quality of life scores favored nitrazepam (<em>P</em> = 0.023). Parasympathetic heart rate variability was significantly higher in nitrazepam responders. Sedation was more common with nitrazepam and irritability with topiramate.</div></div><div><h3>Conclusions</h3><div>Nitrazepam showed superior short-term effectiveness over topiramate in resistant IESS, with better quality of life and autonomic stability. Further research is needed to assess long-term outcomes.</div></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"173 ","pages":"Pages 66-73"},"PeriodicalIF":2.1000,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pediatric neurology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0887899425002607","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Globally, pediatric neurologists vary in their choice of antiseizure medications for children with infantile epileptic spasms syndrome (IESS) who are resistant to hormonal and vigabatrin therapy. This trial aimed to determine whether oral nitrazepam is more effective than oral topiramate in achieving complete cessation of epileptic spasms (ES) in such cases.

Methods

We conducted an open-label, randomized controlled trial with a superiority hypothesis and masked end point assessments. The primary effectiveness end point was complete and sustained cessation of ES for 4 weeks, assessed at 10 weeks post-randomization. Secondary end points included electroclinical remission, time to remission, quality of life (assessed using the Hindi version of the Quality of Life of the Infant scale), autonomic tone (measured via heart rate variability), and adverse events.

Results

Between June 2023 and December 2024, 80 children with resistant IESS were screened and 40 (29 boys, 11 girls) were randomized to receive oral nitrazepam (0.5-3 mg/kg/day; n = 20) or topiramate (2-12 mg/kg/day; n = 20). Complete cessation of ES was achieved in 55% with nitrazepam vs 15% with topiramate (P = 0.019) and electroclinical remission in 45% vs 10% (P = 0.031). Quality of life scores favored nitrazepam (P = 0.023). Parasympathetic heart rate variability was significantly higher in nitrazepam responders. Sedation was more common with nitrazepam and irritability with topiramate.

Conclusions

Nitrazepam showed superior short-term effectiveness over topiramate in resistant IESS, with better quality of life and autonomic stability. Further research is needed to assess long-term outcomes.

查看原文本刊更多论文

尼拉西泮治疗顽固性婴儿癫痫痉挛综合征的概念验证研究（NitRIS试验）

在全球范围内，小儿神经科医生对患有婴儿癫痫痉挛综合征（IESS）的儿童的抗癫痫药物的选择各不相同，这些儿童对激素和维加巴林治疗有抵抗力。本试验旨在确定在这种情况下，口服硝西泮是否比口服托吡酯更有效地实现癫痫痉挛（ES）的完全停止。方法采用开放标签、随机对照试验，采用优势假设和隐匿终点评价。主要有效性终点是ES完全持续停止4周，在随机化后10周进行评估。次要终点包括电临床缓解、缓解时间、生活质量（使用印度版婴儿生活质量量表评估）、自主神经张力（通过心率变异性测量）和不良事件。结果在2023年6月至2024年12月期间，筛选了80名耐药IESS患儿，其中40名（29名男孩，11名女孩）随机接受口服硝西泮（0.5-3 mg/kg/天，n = 20）或托吡酯（2-12 mg/kg/天，n = 20）。硝西泮组ES完全停止的比例为55%，托吡酯组为15% (P = 0.019)，电临床缓解的比例为45%，托吡酯组为10% （P = 0.031）。生活质量评分倾向于硝西泮（P = 0.023）。副交感神经心率变异性在硝西泮应答者中显著升高。硝西泮组镇静更常见，托吡酯组易怒更常见。结论尼硝西泮治疗难治性IESS短期疗效优于托吡酯，生存质量和自主神经稳定性均优于托吡酯。需要进一步的研究来评估长期结果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Pediatric neurology 医学-临床神经学

CiteScore

4.80

自引率

2.60%

发文量

176

审稿时长

78 days

期刊介绍： Pediatric Neurology publishes timely peer-reviewed clinical and research articles covering all aspects of the developing nervous system. Pediatric Neurology features up-to-the-minute publication of the latest advances in the diagnosis, management, and treatment of pediatric neurologic disorders. The journal''s editor, E. Steve Roach, in conjunction with the team of Associate Editors, heads an internationally recognized editorial board, ensuring the most authoritative and extensive coverage of the field. Among the topics covered are: epilepsy, mitochondrial diseases, congenital malformations, chromosomopathies, peripheral neuropathies, perinatal and childhood stroke, cerebral palsy, as well as other diseases affecting the developing nervous system.