Clinical trial NCT04302116: Vigabatrin With High Dose Prednisolone Combination Therapy vs Vigabatrin Alone for Infantile Spasm
Official title: Efficacy of Vigabatrin With High Dose Prednisolone Combination Therapy Versus Vigabatrin Alone for Infantile Spasm: a Randomized Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Infantile Spasm
West Syndrome
Keywords: Infantile Spasm
Vigabatrin
Prednisolone
Treatment
West Syndrome
Lead sponsor: Queen Sirikit National Institute of Child Health
Sponsor class: OTHER_GOV
First posted: 2020-03-10
Enrollment: 250
Sex: ALL
Minimum age (years): 2
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A pragmatic parallel group randomised trial comparing vigabatrin with high dose prednisolone to vigabatrin treatment alone in the treatment of infantile spasm.
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Cessation of spasms
timeFrame: Assessed during Day 14 to Day 42 after treatment.
Secondary outcomes:
measure: Electrographic response
timeFrame: Assessed during Day 14 and Day 43 after treatment.
measure: Electroclinical response
timeFrame: Between Day 14 and Day 21.
measure: Extended electroclinical response
timeFrame: Between Day 42 and Day 49.
measure: The time taken to absence of spasms
timeFrame: Day 1 to Day 14
measure: Relapse of spasms
timeFrame: Day 42 to 3 months after treatment
measure: Adverse reactions
timeFrame: Day 1 to Day 14, from Day 15 to Day 42, and from Day 43 to 4 months into the trial
measure: Epilepsy outcome at age 18 months
timeFrame: From Day 42 to age 18 months
Other outcomes:
Locations:
city: Ratchathewi
country: Thailand
facility: Queen Sirikit National Institute of Child Health
state: Bangkok
Study officials:
affiliation: Queen Sirikit National Institute of Child Health
name: Kullasate Sakpichaisakul, MD
role: PRINCIPAL_INVESTIGATOR
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