In infants with Infantile Epileptic Spasm Syndrome (IESS), does a 7-day course of oral prednisolone followed by a 10-week maintenance therapy achieve comparable short-term and long-term outcomes of IESS and relapse rates compared to a 14-day course of oral prednisolone?

Study setting

The study will be conducted across eight tertiary care hospitals with paediatric neurology units in Sri Lanka. These include the Lady Ridgeway Children’s Hospital (3 units), Colombo North Teaching Hospital, Colombo South Teaching Hospital, Karapitiya Teaching Hospital, Sirimawo Bandaranayake Children’s Hospital, Teaching Hospital Kurunegala, Teaching Hospital Jaffna and Teaching Hospital Anuradhapura. Each unit is equipped with digital video EEG monitoring facilities and is led by a board-certified paediatric neurologist. Participant recruitment will be carried out by either a paediatric neurologist or a paediatrician, with a research assistant coordinating across all units.

Method of randomization

After recruitment, participants are randomly assigned using sealed opaque envelopes to ensure allocation concealment. Each envelope contains one of two treatment packs prepared in advance: Treatment Arm A (Intervention):
• Bag 01: 28 sachets (10?mg each) for the first 7 days
• Bag 02: 30 sachets for the subsequent 15 days
• Bag 03: 20 sachets for the following 10 weeks
(Each bag includes 3 extra sachets in case of vomiting.)

Treatment Arm B (Comparator):
• Bag 01: 28 sachets for the first 7 days
• Bag 02: 28 sachets for the next 7 days
• Bag 03: 30 sachets for the subsequent 15 days
(Each bag includes 3 extra sachets in case of vomiting.)

The sealed envelopes are arranged in a predetermined sequence and distributed to centers by the study statistician. When a patient is recruited, a designated team member (not involved in patient care) opens the next envelope and assigns the treatment accordingly.

Intervention: treatment arm A

The initial phase of the intervention involves administering prednisolone orally at a dosage of 10 mg, four times daily (40 mg/day) for 7 days. This will be followed by a tapering regimen over 15 days (~2 weeks) as outlined below: 10 mg three times daily – 5 days 10 mg twice daily – 5 days 10 mg daily – 5 days

The second phase of the intervention begins at the end of 15 days, where a prolonged tapering of prednisolone at a low dose (<0.4 mg/kg per day) will be administered as 10 mg once daily, twice a week, for an additional 10 weeks.

Comparator (Active): treatment arm B

Prednisone will be administered orally at a dose of 10 mg, four times daily (40 mg/day) for 14 days. This is the standard therapy currently given to children with IESS in Sri Lanka. This will be followed by a tapering regimen over 15 days (~2 weeks) as outlined below: 10 mg three times daily – 5 days 10 mg twice daily – 5 days 10 mg daily – 5 days

No additional tapering will be implemented.

1) male and female infants between ages of 3 to 24 months. 2) Newly confirmed diagnosis of infantile spasms made by the referring paediatrician/ paediatric neurologist based on the diagnostic criteria outlined in the recent ILAE classification and definition of epilepsy syndrome with onset in neonates and infants in 2022. 3) Hypsarrhythmia recorded on pre-treatment EEG. This will be those who show a BASED score of 4 or 5 in a standard EEG performed.

1) Infants with tuberous sclerosis complex^1 2) Ever treated previously for infantile spasms with steroids or other anticonvulsants^2 3) Infants already on steroids or ACTH for any other illness 4) Contraindication for the use of high dose steroids such as underlying infection, immune deficiency, hypertension etc. 5) Children in critical conditions^3 such as severe infections, congenital heart disease or requiring ventilation or care in an ICU 6) Not accompanied by parent/s or parent’s inability to complete follow up^4

^1 A diagnosis or high risk of tuberous sclerosis. (known affected parent, previously diagnosed cardiac rhabdomyoma, hypomelanic macules, forehead fibrous plaque, shagreen patch, retinal phakoma or known polycystic kidneys).

^2 Previous treatments for infantile spasms including a therapeutic trial of pyridoxine to exclude pyridoxine dependent seizures. Note - previous treatment for other seizure types is not a reason for exclusion.

^3 A lethal or potentially lethal condition, other than infantile spasms, with a risk of death before 18 months of age.

^4 Doubt about the ability of the parents or legal guardians to know when the spasms stop.

Important: infants on anticonvulsants therapy (other than steroids) given for treatment of other forms of seizures i.e. neonatal seizures or focal seizures will not be excluded