Clinical trial NCT06838559: Clinical Trial on 7-day Followed by Maintenance Therapy for 10 Weeks vs. 14-day and no Maintenance Course of Prednisolone for the Treatment of Infantile Epileptic Spasms Syndrome (IESS)
Official title: Multicentre, Randomized, Controlled Clinical Trial on 7-day Followed by Maintenance Therapy for 10 Weeks vs. 14-day and no Maintenance Course of Prednisolone for the Treatment of Infantile Epileptic Spasms Syndrome (IESS)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Spasms, Infantile
Prednisolone
Keywords: Randomized controlled trial
Spasms, Infantile
Prednisolone
Infant
Electroencephalography
Child Development
Relapse
Tapering Regimen
Treatment Duration
Lead sponsor: University of Colombo
Sponsor class: OTHER
First posted: 2025-02-20
Enrollment: 182
Sex: ALL
Minimum age (years): 3
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized (1:1), single-blinded, multi-centre, parallel-group clinical trial.
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to learn if short courses (7 days) of oral prednisolone are as effective as longer courses (14 days) in treating Infantile Epileptic Spasms Syndrome (IESS) in infants. The main questions it aims to answer are:

1. Does a 7-day course of oral prednisolone result in a similar or better reduction in spasm frequency compared to a 14-day course?
2. Does the duration of treatment (7 vs. 14 days) influence relapse rates and developmental outcomes in infants with IESS?
3. Researchers will compare the effects of the two treatment arms (7-day course vs. 14-day course of oral prednisolone) to see if there is a difference in efficacy and safety.

Participants will:

1. Receive either a 7-day or 14-day course of oral prednisolone as part of their treatment
2. Be monitored for spasm frequency and any side effects during hospital observation for the first 48 hours
3. Maintain a spasm diary during the treatment period to track spasm frequency
4. Return for follow-up visits at 7 days, 14 days, 28 days, 42 days, 3 months, 6 months, and 12 months to assess treatment response, relapse, and developmental outcomes

Detailed description: Study Title: Comparison of Short (7-Day) versus Long (14-Day) Courses of Oral Prednisolone in the Treatment of Infantile Epileptic Spasms Syndrome (IESS)

Study Overview: This is a clinical trial designed to compare the efficacy and safety of two treatment regimens using oral prednisolone for infants with Infantile Epileptic Spasms Syndrome (IESS). The study aims to evaluate the impact of treatment duration (7 days vs. 14 days) on spasm resolution, relapse rates, and developmental outcomes in infants with IESS. Participants will be randomized into two treatment arms to receive either a 7-day or 14-day course of oral prednisolone, and they will be followed for a year to assess outcomes related to spasm control, relapse, adverse effects, and long-term development.

Study Population: The study will include infants diagnosed with IESS, aged 3 to 24 months, who are receiving care at participating clinical sites. Eligibility criteria ensure the inclusion of infants with confirmed spasms, with or without known aetiology, and those who have not previously received systemic treatment for IESS.

Objectives:

* Primary Objective: To compare the effectiveness of 7-day versus 14-day oral prednisolone treatment in reducing spasm frequency in infants with IESS.
* Secondary Objectives: To evaluate the impact of treatment duration on relapse rates, developmental outcomes, and adverse effects.
* Exploratory Objectives: To assess any differences in long-term neurodevelopmental progress, including cognitive and motor development, and to compare EEG findings between treatment groups.

Methodology:

1. Randomization: Participants will be randomly assigned to receive either 7 days or 14 days of oral prednisolone, with blinding for the treatment duration.
2. Treatment Regimen:

   * Intervention Arm (7-Day Course): Participants will receive 3 mg/kg/day of oral prednisolone for 7 days.
   * Comparator Arm (14-Day Course): Participants will receive 3 mg/kg/day of oral prednisolone for 14 days.
   * In both arms, after 48 hours of in-hospital treatment, participants will be monitored for side effects, and parents will be educated on medication administration and spasm monitoring.
3. Adverse Event Monitoring: Adverse events will be tracked throughout the trial, with particular attention to common side effects associated with prednisolone use, including irritability, weight gain, and gastric irritation. Serious adverse events will be carefully documented and managed.
4. Follow-Up: Follow-up visits will be conducted at 7 days, 14 days, 28 days, 42 days, 3 months, 6 months, and 12 months to monitor spasm control, relapse, and developmental progress. At 24 months, a comprehensive developmental assessment will be conducted to evaluate the long-term effects of the treatment.

Inclusion and Exclusion Criteria:

* Inclusion Criteria: Infants diagnosed with IESS, aged 2 to 24 months, with confirmed spasms either due to a known or unknown aetiology.
* Exclusion Criteria: Infants with a history of other significant neurological conditions, or who are contraindicated for oral prednisolone, including those with uncontrolled systemic infections, significant cardiovascular disease, or severe hypertension.

Data Collection:

Baseline Data: Clinical history, imaging (CT or MRI), and EEG results will be collected to help categorize participants into known or undetermined aetiology groups. A metabolic screening will be conducted for infants with undetermined aetiology.

Eligibility criteria: Inclusion Criteria:

* Infants between ages of 3 to 24 months
* Newly confirmed diagnosis of infantile epileptic spasms syndrome 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
* Hypsarrhythmia recorded on pre-treatment EEG. This will be those who show a BASED score of 4 or 5 in a standard EEG

Exclusion Criteria:

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

Primary outcomes:
measure: Electroclinical Remission at Day 14 and Day 28
timeFrame: Assessed at 14 days and 28 days after treatment initiation.
Secondary outcomes:
measure: Long-Term Spasm Control
timeFrame: Assessed at 42 days, 3 months, 6 months, and 12 months post-treatment.
measure: Spasm Relapse Rate and Time to Relapse
timeFrame: Evaluated continuously over the 12-month follow-up period.
measure: Developmental Outcome at 24 Months
timeFrame: Assessed at 24 months following treatment initiation.
measure: Evolution of Epilepsy
timeFrame: Assessed at 12 months post-treatment.
Other outcomes:
Locations:
city: Peradeniya
country: Sri Lanka
facility: Sirimavo Bandaranayake Specialized Children's Hospital
state: Central Province
city: Anuradhapura
country: Sri Lanka
facility: Teaching Hospital Anuradhapura
state: North Central Province
city: Jaffna
country: Sri Lanka
facility: Teaching Hospital - Jaffna
state: Northern Province
city: Galle
country: Sri Lanka
facility: Teaching Hospital - Karapitiya
state: Southern Province
city: Colombo
country: Sri Lanka
facility: Lady Ridgeway Hospital for Children
state: Western Province
city: Kalubowila
country: Sri Lanka
facility: Colombo South Teaching Hospital
state: Western Province
city: Ragama
country: Sri Lanka
facility: Colombo North Teaching Hospital
state: Western Province
Study officials:
affiliation: Department of Paediatrics at the Faculty of Medicine, University of Colombo, Sri Lanka
name: Jithangi Wanigasinghe, MD, MPhil
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Community Medicine, Faculty of Medicine, University of Colombo, Sri Lanka
name: Carukshi Arambepola, MSc, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Pharmacology, Faculty of Medicine, University of Colombo, Sri Lanka
name: Shalini Sri Ranganathan, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Paediatrics, University of Sri Jayewardenepura, Sri Lanka
name: Nimesha Gamhewage, MD, DCH
role: PRINCIPAL_INVESTIGATOR
References: