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

NCT04302116 | Recruiting

• 1 other identifier: QSNICH63-008
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Infantile Spasm; West Syndrome

Keywords

Infantile Spasm; Vigabatrin; Prednisolone; Treatment; West Syndrome

Outcome Measures

Primary Outcomes (1)

• Cessation of spasms

  Defined as no witnessed spasms (either clusters or single spasms) from Day 14 to Day 42 inclusive.

  Assessed during Day 14 to Day 42 after treatment.

Secondary Outcomes (7)

• Electrographic response

  Assessed during Day 14 and Day 43 after treatment.

• Electroclinical response

  Between Day 14 and Day 21.

• Extended electroclinical response

  Between Day 42 and Day 49.

• The time taken to absence of spasms

  Day 1 to Day 14

• Relapse of spasms

  Day 42 to 3 months after treatment

Study Arms (2)

Combination therapy with vigabatrin and prednisolone

EXPERIMENTAL

Vigabatrin (tablet of 500 mg) dose based on weight divided in two times. The protocol for vigabatrin dose is 50 mg/kg/day at Day 1, 100 mg/kg/day at Day 2, and increase to 150 mg/kg/day if seizures still occur after 72 hours after treatment. Vigabatrin will be continued for 3 months, then reduced and completely off within 4 weeks. Prednisolone (tablet of 5 mg), 40 mg of prednisolone (10 mg oral 4 times a day) for 14 days. Prednisolone will be increased to 60 mg/day (20 mg oral 3 times a day) if seizures still occur at Day 7 or recur within Day 8 - 14. Then, prednisolone will be reduced every 5 day until completely off within 1 month. Total prednisolone duration is 1 month.

Drug: Combination therapy with vigabatrin and prednisolone

Vigabatrin alone

ACTIVE COMPARATOR

Vigabatrin (500 mg/tab) dose will be calculated on weight basis divided in two times. The protocol for vigabatrin dose is 50 mg/kg/day at Day 1, 100 mg/kg/day at Day 2, and increase to 150 mg/kg/day if seizures still occur after 72 hours after treatment. Vigabatrin will be continued for 3 months, then reduced and completely off within 4 weeks.

Drug: Vigabatrin Tablets

Interventions

Combination therapy with vigabatrin and prednisolone DRUG

High dose prednisolone (40 - 60 mg/day) for 1 month combined with vigabatrin treatment (50-150 mg/kg/day) twice daily for 4 months

Also known as: Sabril with prednisolone

Combination therapy with vigabatrin and prednisolone

Vigabatrin Tablets DRUG

Vigabatrin (50-150 mg/kg/day) twice daily for 4 months

Also known as: Sabril

Vigabatrin alone

Eligibility Criteria

• Age: 2 Months - 14 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Kullasate Sakpichaisakul: lead

Study Sites (1)

Queen Sirikit National Institute of Child Health

Ratchathewi, Bangkok, 10400, Thailand

RECRUITING

Related Publications (27)

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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.

  PMID: 15159460 RESULT

• 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 RESULT

• 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.

  PMID: 29105055 RESULT

• 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.

  PMID: 22859699 RESULT

• 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.

  PMID: 22689735 RESULT

• 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.

  PMID: 26302697 RESULT

• 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.

  PMID: 8681895 RESULT

• 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.

  PMID: 10565592 RESULT

• 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.

  PMID: 11673582 RESULT

• 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.

  PMID: 21070215 RESULT

• 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.

  PMID: 15541450 RESULT

• Snead OC 3rd, Benton JW, Myers GJ. ACTH and prednisone in childhood seizure disorders. Neurology. 1983 Aug;33(8):966-70. doi: 10.1212/wnl.33.8.966.

  PMID: 6308515 RESULT

• 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.

  PMID: 8604274 RESULT

• 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.

  PMID: 24657009 RESULT

• 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.

  PMID: 26216500 RESULT

• 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.

  PMID: 27838190 RESULT

• 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.

  PMID: 29966811 RESULT

• 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.

  PMID: 26280806 RESULT

• Kankirawatana P, Raksadawan N, Balangkura K. Vigabatrin therapy in infantile spasms. J Med Assoc Thai. 2002 Aug;85 Suppl 2:S778-83.

  PMID: 12403260 RESULT

• Visudtibhan A, Chiemchanya S, Visudhiphan P, Phusirimongkol S. Vigabatrin in infantile spasms: preliminary result. J Med Assoc Thai. 1999 Oct;82(10):1000-5.

  PMID: 10561962 RESULT

• 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.

  PMID: 40116235 DERIVED

Related Links

• Clinical practice guidelines for epilepsy by Epilepsy Society of Thailand

MeSH Terms

Conditions

Spasms, Infantile

Interventions

Combined Modality Therapy; Vigabatrin; Prednisolone

Condition Hierarchy (Ancestors)

Epilepsy, Generalized; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes

Intervention Hierarchy (Ancestors)

Therapeutics; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Kullasate Sakpichaisakul, MD

  Queen Sirikit National Institute of Child Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kullasate Sakpichaisakul, MD

CONTACT

66-2-354-8333; kullasate.s@rsu.ac.th

Sirorat Suwannachote, MD

CONTACT

66-2-354-8333; sirorat.s@rsu.ac.th

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Each patient will visit the clinic at Day 8, 14, 43, and 3 months by outcome assessor who is blinded for treatment to determine seizure frequency and adverse events. Those patients will be seen and under taking care of primary neurologists and pharmacists who are not blinded to treatment at the same visit as a standard clinical practice and check with compliance and adjust vigabatrin or prednisolone following each treatment allocated (if needed). Family or caregivers will not be blinded to treatment. EEG will be scored using BASED scores at Day 0 (before treatment), 14, and 43 to assess the resolution of hypsarrhythmia.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Pediatric epileptologist

Model Details: A pragmatic parallel group randomised trial comparing vigabatrin with high dose prednisolone to vigabatrin treatment alone in the treatment of infantile spasm.

Study Record Dates

• First Submitted: March 5, 2020
• First Posted: March 10, 2020
• Study Start: May 18, 2020
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: August 25, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

TH (1)