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

NCT ID: NCT04302116

Last Updated: 2021-08-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

250 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-05-18

Study Completion Date

2026-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Infantile Spasm West Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

A pragmatic parallel group randomised trial comparing vigabatrin with high dose prednisolone to vigabatrin treatment alone in the treatment of infantile spasm.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Investigators Outcome Assessors
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.

Study Groups

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Combination therapy with vigabatrin and prednisolone

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.

Group Type EXPERIMENTAL

Combination therapy with vigabatrin and prednisolone

Intervention Type 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

Vigabatrin alone

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.

Group Type ACTIVE_COMPARATOR

Vigabatrin Tablets

Intervention Type DRUG

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

Interventions

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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

Intervention Type DRUG

Vigabatrin Tablets

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

Intervention Type DRUG

Other Intervention Names

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Sabril with prednisolone Sabril

Eligibility Criteria

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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
Minimum Eligible Age

2 Months

Maximum Eligible Age

14 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Kullasate Sakpichaisakul

OTHER_GOV

Sponsor Role lead

Responsible Party

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Kullasate Sakpichaisakul

Pediatric epileptologist

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Kullasate Sakpichaisakul, MD

Role: PRINCIPAL_INVESTIGATOR

Queen Sirikit National Institute of Child Health

Locations

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Queen Sirikit National Institute of Child Health

Ratchathewi, Bangkok, Thailand

Site Status RECRUITING

Countries

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Thailand

Central Contacts

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Kullasate Sakpichaisakul, MD

Role: CONTACT

66-2-354-8333

Sirorat Suwannachote, MD

Role: CONTACT

66-2-354-8333

Facility Contacts

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Kullasate Sakpichaisakul, MD

Role: primary

Kantapon Trongkamolchai, MD

Role: backup

References

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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.

Reference Type DERIVED
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Other Identifiers

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QSNICH63-008

Identifier Type: -

Identifier Source: org_study_id

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