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

Summary

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.

Timeline

Start

2020-05-18

Primary completion

2026-06

Completion

2026-12

Publications

• Results 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.
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• Results 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.
• Results 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.
• Results 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.
• Results 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: 10.1212/01.wnl.0000127773.72699.c8.
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• Results Demarest ST, Shellhaas RA, Gaillard WD, Keator C, Nickels KC, Hussain SA, Loddenkemper T, Patel AD, Saneto RP, Wirrell E, Sanchez Fernandez I, Chu CJ, Grinspan Z, Wusthoff CJ, Joshi S, Mohamed IS, Stafstrom CE, Stack CV, Yozawitz E, Bluvstein JS, Singh RK, Knupp KG; Pediatric Epilepsy Research Consortium. The impact of hypsarrhythmia on infantile spasms treatment response: Observational cohort study from the National Infantile Spasms Consortium. Epilepsia. 2017 Dec;58(12):2098-2103. doi: 10.1111/epi.13937. Epub 2017 Nov 3.
• Results Arya R, Shinnar S, Glauser TA. Corticosteroids for the treatment of infantile spasms: a systematic review. J Child Neurol. 2012 Oct;27(10):1284-8. doi: 10.1177/0883073812453203. Epub 2012 Aug 1.
• Results Go CY, Mackay MT, Weiss SK, Stephens D, Adams-Webber T, Ashwal S, Snead OC 3rd; Child Neurology Society; American Academy of Neurology. Evidence-based guideline update: medical treatment of infantile spasms [RETIRED]. Report of the Guideline Development Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2012 Jun 12;78(24):1974-80. doi: 10.1212/WNL.0b013e318259e2cf.
• Results Mytinger JR, Camfield PR. Synthetic ACTH Is Not Superior to Prednisolone for Infantile Spasms: Randomized Clinical Trials and Tribulations. Pediatr Neurol. 2015 Sep;53(3):181-2. doi: 10.1016/j.pediatrneurol.2015.07.005. Epub 2015 Jul 22. No abstract available.
• Results Aicardi J, Mumford JP, Dumas C, Wood S. Vigabatrin as initial therapy for infantile spasms: a European retrospective survey. Sabril IS Investigator and Peer Review Groups. Epilepsia. 1996 Jul;37(7):638-42. doi: 10.1111/j.1528-1157.1996.tb00627.x.
• Results Appleton RE, Peters AC, Mumford JP, Shaw DE. Randomised, placebo-controlled study of vigabatrin as first-line treatment of infantile spasms. Epilepsia. 1999 Nov;40(11):1627-33. doi: 10.1111/j.1528-1157.1999.tb02049.x.
• Results Elterman RD, Shields WD, Mansfield KA, Nakagawa J; US Infantile Spasms Vigabatrin Study Group. Randomized trial of vigabatrin in patients with infantile spasms. Neurology. 2001 Oct 23;57(8):1416-21. doi: 10.1212/wnl.57.8.1416.
• Results Maguire MJ, Hemming K, Wild JM, Hutton JL, Marson AG. Prevalence of visual field loss following exposure to vigabatrin therapy: a systematic review. Epilepsia. 2010 Dec;51(12):2423-31. doi: 10.1111/j.1528-1167.2010.02772.x. Epub 2010 Nov 10.
• Results Lux AL, Edwards SW, Hancock E, Johnson AL, Kennedy CR, Newton RW, O'Callaghan FJ, Verity CM, Osborne JP. The United Kingdom Infantile Spasms Study comparing vigabatrin with prednisolone or tetracosactide at 14 days: a multicentre, randomised controlled trial. Lancet. 2004 Nov 13-19;364(9447):1773-8. doi: 10.1016/S0140-6736(04)17400-X.
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• Results Baram TZ, Mitchell WG, Tournay A, Snead OC, Hanson RA, Horton EJ. High-dose corticotropin (ACTH) versus prednisone for infantile spasms: a prospective, randomized, blinded study. Pediatrics. 1996 Mar;97(3):375-9.
• Results Yi ZS, Wu HP, Yu XY, Chen Y, Zhong JM. Efficacy and tolerability of high-dose prednisone in Chinese children with infantile spasms. Brain Dev. 2015 Jan;37(1):23-8. doi: 10.1016/j.braindev.2014.02.005. Epub 2014 Mar 20.
• Results Wanigasinghe J, Arambepola C, Sri Ranganathan S, Sumanasena S, Attanapola G. Randomized, Single-Blind, Parallel Clinical Trial on Efficacy of Oral Prednisolone Versus Intramuscular Corticotropin on Immediate and Continued Spasm Control in West Syndrome. Pediatr Neurol. 2015 Sep;53(3):193-9. doi: 10.1016/j.pediatrneurol.2015.05.004. Epub 2015 Jun 26.
• Results O'Callaghan FJ, Edwards SW, Alber FD, Hancock E, Johnson AL, Kennedy CR, Likeman M, Lux AL, Mackay M, Mallick AA, Newton RW, Nolan M, Pressler R, Rating D, Schmitt B, Verity CM, Osborne JP; participating investigators. Safety and effectiveness of hormonal treatment versus hormonal treatment with vigabatrin for infantile spasms (ICISS): a randomised, multicentre, open-label trial. Lancet Neurol. 2017 Jan;16(1):33-42. doi: 10.1016/S1474-4422(16)30294-0. Epub 2016 Nov 10.
• Results Ko A, Youn SE, Chung HJ, Kim SH, Lee JS, Kim HD, Kang HC. Vigabatrin and high-dose prednisolone therapy for patients with West syndrome. Epilepsy Res. 2018 Sep;145:127-133. doi: 10.1016/j.eplepsyres.2018.06.013. Epub 2018 Jun 23.
• Results Mytinger JR, Hussain SA, Islam MP, Millichap JJ, Patel AD, Ryan NR, Twanow JD, Heyer GL. Improving the inter-rater agreement of hypsarrhythmia using a simplified EEG grading scale for children with infantile spasms. Epilepsy Res. 2015 Oct;116:93-8. doi: 10.1016/j.eplepsyres.2015.07.008. Epub 2015 Jul 28.
• Results Kankirawatana P, Raksadawan N, Balangkura K. Vigabatrin therapy in infantile spasms. J Med Assoc Thai. 2002 Aug;85 Suppl 2:S778-83.
• Results Visudtibhan A, Chiemchanya S, Visudhiphan P, Phusirimongkol S. Vigabatrin in infantile spasms: preliminary result. J Med Assoc Thai. 1999 Oct;82(10):1000-5.
• Boonkrongsak R, Trongkamolchai K, Suwannachote S, Sri-Udomkajorn S, Wittawassamrankul R, Arya R, Sakpichaisakul K. Combination Therapy With Vigabatrin and Prednisolone Versus Vigabatrin Alone for Infantile Spasms. Ann Clin Transl Neurol. 2025 May;12(5):1012-1021. doi: 10.1002/acn3.70034. Epub 2025 Mar 21.

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