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

Infantile Spasm Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04302116
• Other study ID #: QSNICH63-008
• Status: Recruiting
• Phase: N/A
• Start date: May 18, 2020
• Est. completion date: December 2026

Study information

• Verified date: August 2021
• Source: Queen Sirikit National Institute of Child Health
• Contact: Kullasate Sakpichaisakul, MD
• Phone: 66-2-354-8333
• Email: kullasate.s[@]rsu.ac.th
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: December 2026
• Est. primary completion date: June 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Months to 14 Months

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Infantile Spasm
• Muscle Cramp
• Spasm
• Spasms, Infantile
• West Syndrome

Intervention

Drug:
• 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
• Vigabatrin Tablets
Vigabatrin (50-150 mg/kg/day) twice daily for 4 months

Locations

Country	Name	City	State
Thailand	Queen Sirikit National Institute of Child Health	Ratchathewi	Bangkok

Sponsors (1)

Lead Sponsor	Collaborator
Kullasate Sakpichaisakul

Country where clinical trial is conducted

Thailand, 

References & Publications (26)

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. — View Citation

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. — View Citation

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. Epub 2012 Aug 1. Review. — View Citation

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. — View Citation

Demarest ST, Shellhaas RA, Gaillard WD, Keator C, Nickels KC, Hussain SA, Loddenkemper T, Patel AD, Saneto RP, Wirrell E, Sánchez Fernández I, Chu CJ, Grinspan Z, Wusthoff CJ, Joshi S, Mohamed IS, Stafstrom CE, Stack CV, Yozawitz E, Bluvstein JS, Singh RK — View Citation

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. — View Citation

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. Report of the Guideline Development Subcommitte — View Citation

Hrachovy RA, Frost JD Jr, Kellaway P. Hypsarrhythmia: variations on the theme. Epilepsia. 1984 Jun;25(3):317-25. — View Citation

Hrachovy RA, Frost JD Jr. Infantile epileptic encephalopathy with hypsarrhythmia (infantile spasms/West syndrome). J Clin Neurophysiol. 2003 Nov-Dec;20(6):408-25. Review. — View Citation

Jeavons PM, Bower BD, Dimitrakoudi M. Long-term prognosis of 150 cases of "West syndrome". Epilepsia. 1973 Jun;14(2):153-64. — View Citation

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

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. — View Citation

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 tr — View Citation

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. Review. — View Citation

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 treat — View Citation

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. Review. — View Citation

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. — View Citation

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: 1 — View Citation

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 — View Citation

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.152 — View Citation

Snead OC 3rd, Benton JW, Myers GJ. ACTH and prednisone in childhood seizure disorders. Neurology. 1983 Aug;33(8):966-70. — View Citation

Trevathan E, Murphy CC, Yeargin-Allsopp M. The descriptive epidemiology of infantile spasms among Atlanta children. Epilepsia. 1999 Jun;40(6):748-51. — View Citation

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

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. P — View Citation

Wheless JW, Clarke DF, Arzimanoglou A, Carpenter D. Treatment of pediatric epilepsy: European expert opinion, 2007. Epileptic Disord. 2007 Dec;9(4):353-412. Review. — View Citation

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. — View Citation

* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Electrographic response	Disappearance of hypsarrhythmia defined by Burden of Amplitudes and Epileptiform Discharges (BASED) scoring system < 2 at Day 14 and Day 43 after treatment.	Assessed during Day 14 and Day 43 after treatment.
Secondary	Electroclinical response	the cessation of spasms with the addition of absence of hypsarrhythmia (BASED score < 2) on the Day 14 EEG. Valid Day 14 EEGs will be undertaken between Day 14 and Day 21 inclusive.	Between Day 14 and Day 21.
Secondary	Extended electroclinical response	Electroclinical response with the addition of absence of hypsarrhythmia (BASED score < 2) on the Day 42 EEG. Valid Day 42 EEGs will be undertaken between Day 42 and Day 49 inclusive.	Between Day 42 and Day 49.
Secondary	The time taken to absence of spasms	Duration for clinical cessation of spasms after initiation treatment	Day 1 to Day 14
Secondary	Relapse of spasms	Defined when a cluster of more than one spasm in reported after Day 42. No EEG is required.	Day 42 to 3 months after treatment
Secondary	Adverse reactions	Each adverse event will be evaluated by the principal investigator to determine whether in their view it is an adverse reaction. If considered an adverse reaction, it will be reported by using the standard classification.	Day 1 to Day 14, from Day 15 to Day 42, and from Day 43 to 4 months into the trial
Secondary	Epilepsy outcome at age 18 months	Epilepsy status and antiepileptic drugs (AEDs) will be recorded by using the following categories: 1) Infantile spasms (clusters of spasms), 2) Any other epileptic seizure including febrile seizures, and 3) Names of any preventive AEDs prescribed	From Day 42 to age 18 months

External Links

•   Clinical practice guidelines for epilepsy by Epilepsy Society of Thailand