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

Kullasate Sakpichaisakul

Status: Enrolling

Conditions: Infantile Spasm; West Syndrome

Treatments: Drug: Combination therapy with vigabatrin and prednisolone; Drug: Vigabatrin Tablets

Study type: Interventional

Funder types: Other

Identifiers

NCT04302116

QSNICH63-008

Details and patient eligibility

About

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.

Full 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.

Enrollment: 250 estimated patients

Sex: All

Ages: 2 to 14 months old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

250 participants in 2 patient groups

Combination therapy with vigabatrin and prednisolone

Experimental group

Description:

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.

Treatment:

Drug: Combination therapy with vigabatrin and prednisolone

Vigabatrin alone

Active Comparator group

Description:

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.

Treatment:

Drug: Vigabatrin Tablets