Vigabatrin With High Dose Prednisolone Combination Therapy vs Vigabatrin Alone for Infantile Spasm

Официальное название

Efficacy of Vigabatrin With High Dose Prednisolone Combination Therapy Versus Vigabatrin Alone for Infantile Spasm: a Randomized Trial

Обзор

Infantile spasms (IS) are seizures associated with a severe infantile epileptic encephalopathy. Both cessation of spasms and electrographic response are necessary for the best neurodevelopmental outcomes. Adrenocorticotrophic hormone (ACTH), or prednisolone, or vigabatrin are considered the first-line treatment individually. However, ACTH expense and availability are the barriers in developing countries including Thailand. Vigabatrin, therefore, is the first recommended by Epilepsy Society of Thailand due to ACTH unavailability. Recently, combined steroid treatments (either ACTH or high dose prednisolone) with vigabatrin are superior in cessation of spasms compared to steroid treatment alone. Thus, this study is aimed to compare the efficacy of vigabatrin with high dose prednisolone combination therapy and vigabatrin alone.

Подробное описание

Infantile spasms are recognized as epileptic encephalopathy which include the hypsarrhythmia or variants electroencephalographic (EEG) features and psychomotor regression. Various underlying conditions are associated with the infantile spasm included cerebral malformation, hypoxic ischemic encephalopathy, genetic disorders (Down syndrome), tuberous sclerosis complex (TSC), etc. Although vigabatrin has the evidence to use as the first line treatment for infantile spasm related with TSC. Adrenocorticotrophic hormone (ACTH), or high dose prednisolone, or vigabatrin are the first line treatment of IS in non-TSC.

The effectiveness of ACTH versus high dose prednisolone question have not yet definitely answered. Furthermore, ACTH expense and availability are the barriers in developing countries including Thailand. Vigabatrin, therefore, is the first option of therapy recommended by Epilepsy Society of Thailand due to ACTH unavailability. Recently, combined steroid treatments (either ACTH or high dose prednisolone) with vigabatrin are superior in cessation of spasms compared to steroid treatment alone. Questions about the clinical cessation of IS and electrographic remission by combination treatment with vigabatrin and high dose prednisolone compare to vigabatrin alone have not fully elucidated. Thus, this study is aimed to compare the efficacy of vigabatrin with high dose prednisolone combination therapy and vigabatrin alone.

Вмешательства

• Препарат Combination therapy with vigabatrin and prednisolone
  High dose prednisolone (40 - 60 mg/day) for 1 month combined with vigabatrin treatment (50-150 mg/kg/day) twice daily for 4 months
• Препарат Vigabatrin Tablets
  Vigabatrin (50-150 mg/kg/day) twice daily for 4 months

Первичные конечные точки

• Cessation of spasms [Срок оценки: Assessed during Day 14 to Day 42 after treatment.]

Вторичные конечные точки (7)

• Electrographic response [Срок оценки: Assessed during Day 14 and Day 43 after treatment.]
• Electroclinical response [Срок оценки: Between Day 14 and Day 21.]
• Extended electroclinical response [Срок оценки: Between Day 42 and Day 49.]
• The time taken to absence of spasms [Срок оценки: Day 1 to Day 14]
• Relapse of spasms [Срок оценки: Day 42 to 3 months after treatment]
• Adverse reactions [Срок оценки: Day 1 to Day 14, from Day 15 to Day 42, and from Day 43 to 4 months into the trial]
• Epilepsy outcome at age 18 months [Срок оценки: From Day 42 to age 18 months]

Критерии участия

Критерии включения

• Age at 2-14 months at date of enrollment
• Clinical diagnosis of infantile spasm assessed by pediatric neurologist and hypsarrhythmic pattern or variants interpreted by pediatric epileptologist
• Thai nationality

Критерии исключения

• Previous treatment (within the last 28 days) with vigabatrin or corticosteroid
• Previous diagnosis of epileptic encephalopathy e.g. early infantile epileptic encephalopathy and early myoclonic epileptic encephalopathy
• Has a clinical suspicious or diagnosis of tuberous sclerosis complex characterized by one of these; known affected parent, previously diagnosed cardiac rhabdomyoma, hypomelanotic macules, forehead fibrous plaque, shagreen patch, retinal phakoma, or known polycystic kidneys
• A contraindication to vigabatrin or corticosteroid such as recent varicella or herpes zoster infection, gastrointestinal hemorrhage etc.
• Thai language ability of the parents or guardians is that they may not understand what is being requested of them.
• Predictable lack of availability of follow up

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Таиланд · 1 центр

• Queen Sirikit National Institute of Child Health — Ratchathewi

Публикации

• Hrachovy RA, Frost JD Jr. Infantile epileptic encephalopathy with hypsarrhythmia (infantile spasms/West syndrome). J Clin Neurophysiol. 2003 Nov-Dec;20(6):408-25. doi: 10.1097/00004691-200311000-00004. PMID 14734931
• Jeavons PM, Bower BD, Dimitrakoudi M. Long-term prognosis of 150 cases of "West syndrome". Epilepsia. 1973 Jun;14(2):153-64. doi: 10.1111/j.1528-1157.1973.tb03952.x. No abstract available. PMID 4515986
• Trevathan E, Murphy CC, Yeargin-Allsopp M. The descriptive epidemiology of infantile spasms among Atlanta children. Epilepsia. 1999 Jun;40(6):748-51. doi: 10.1111/j.1528-1157.1999.tb00773.x. PMID 10368073
• Hrachovy RA, Frost JD Jr, Kellaway P. Hypsarrhythmia: variations on the theme. Epilepsia. 1984 Jun;25(3):317-25. doi: 10.1111/j.1528-1157.1984.tb04195.x. PMID 6539199
• Pellock JM, Hrachovy R, Shinnar S, Baram TZ, Bettis D, Dlugos DJ, Gaillard WD, Gibson PA, Holmes GL, Nordl DR, O'Dell C, Shields WD, Trevathan E, Wheless JW. Infantile spasms: a U.S. consensus report. Epilepsia. 2010 Oct;51(10):2175-89. doi: 10.1111/j.1528-1167.2010.02657.x. PMID 20608959
• Lux AL, Osborne JP. A proposal for case definitions and outcome measures in studies of infantile spasms and West syndrome: consensus statement of the West Delphi group. Epilepsia. 2004 Nov;45(11):1416-28. doi: 10.1111/j.0013-9580.2004.02404.x. PMID 15509243
• Mackay MT, Weiss SK, Adams-Webber T, Ashwal S, Stephens D, Ballaban-Gill K, Baram TZ, Duchowny M, Hirtz D, Pellock JM, Shields WD, Shinnar S, Wyllie E, Snead OC 3rd; American Academy of Neurology; Child Neurology Society. Practice parameter: medical treatment of infantile spasms: report of the American Academy of Neurology and the Child Neurology Society. Neurology. 2004 May 25;62(10):1668-81. doi PMID 15159460
• Wheless JW, Clarke DF, Arzimanoglou A, Carpenter D. Treatment of pediatric epilepsy: European expert opinion, 2007. Epileptic Disord. 2007 Dec;9(4):353-412. doi: 10.1684/epd.2007.0144. PMID 18077226

Идентификаторы

NCT: NCT04302116 · QSNICH63-008

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗