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)

NCT ID: NCT06838559

Last Updated: 2025-02-24

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 182 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-01
• Study Completion Date: 2027-12-31

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.

Conditions

Spasms, Infantile; Prednisolone

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

Short-Duration Oral Prednisolone with Extended Tapering

Intervention Type: DRUG

In treatment arm A, oral prednisolone will be administered in tablet form (5 mg strength) as follows: an initial phase of 10 mg four times daily (total 40 mg/day) for 7 days, followed by a 15-day tapering phase-10 mg three times daily for 5 days, 10 mg twice daily for 5 days, and 10 mg once daily for 5 days. After tapering, a prolonged low-dose maintenance phase will be implemented, where 10 mg is given once daily twice a week for an additional 10 weeks. This regimen is designed to test whether a shorter high-dose course, combined with extended low-dose maintenance, can provide equivalent control of infantile epileptic spasms syndrome while reducing the adverse effects associated with longer high-dose therapy, compared to the standard 14-day high-dose regimen (treatment arm B).

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.

Group Type: ACTIVE_COMPARATOR

Standard Oral Prednisolone Regimen with Tapering

Intervention Type: DRUG

Prednisone oral tablets, 10 mg, administered four times daily (40 mg/day) for 14 days, followed by a tapering phase over 15 days: 10 mg three times daily for 5 days, 10 mg twice daily for 5 days, and 10 mg once daily for 5 days. No further tapering will be implemented after the initial 14-day treatment period. This regimen represents the standard therapy for Infantile Spasms in Sri Lanka.

Interventions

Short-Duration Oral Prednisolone with Extended Tapering

In treatment arm A, oral prednisolone will be administered in tablet form (5 mg strength) as follows: an initial phase of 10 mg four times daily (total 40 mg/day) for 7 days, followed by a 15-day tapering phase-10 mg three times daily for 5 days, 10 mg twice daily for 5 days, and 10 mg once daily for 5 days. After tapering, a prolonged low-dose maintenance phase will be implemented, where 10 mg is given once daily twice a week for an additional 10 weeks. This regimen is designed to test whether a shorter high-dose course, combined with extended low-dose maintenance, can provide equivalent control of infantile epileptic spasms syndrome while reducing the adverse effects associated with longer high-dose therapy, compared to the standard 14-day high-dose regimen (treatment arm B).

Intervention Type: DRUG

Standard Oral Prednisolone Regimen with Tapering

Prednisone oral tablets, 10 mg, administered four times daily (40 mg/day) for 14 days, followed by a tapering phase over 15 days: 10 mg three times daily for 5 days, 10 mg twice daily for 5 days, and 10 mg once daily for 5 days. No further tapering will be implemented after the initial 14-day treatment period. This regimen represents the standard therapy for Infantile Spasms in Sri Lanka.

Intervention Type: DRUG

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

• Minimum Eligible Age: 3 Months
• Maximum Eligible Age: 24 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Colombo

OTHER

Sponsor Role: lead

Responsible Party

Jithangi Wanigasinghe

Professor in Paediatric Neurology, Department of Paediatrics, Faculty of Medicine, University of Colombo, Sri Lanka

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jithangi Wanigasinghe, MD, MPhil

Role: PRINCIPAL_INVESTIGATOR

Department of Paediatrics at the Faculty of Medicine, University of Colombo, Sri Lanka

Carukshi Arambepola, MSc, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Community Medicine, Faculty of Medicine, University of Colombo, Sri Lanka

Shalini Sri Ranganathan, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Pharmacology, Faculty of Medicine, University of Colombo, Sri Lanka

Nimesha Gamhewage, MD, DCH

Role: PRINCIPAL_INVESTIGATOR

Department of Paediatrics, University of Sri Jayewardenepura, Sri Lanka

Locations

Sirimavo Bandaranayake Specialized Children's Hospital

Peradeniya, Central Province, Sri Lanka

Teaching Hospital Anuradhapura

Anuradhapura, North Central Province, Sri Lanka

Teaching Hospital - Jaffna

Jaffna, Northern Province, Sri Lanka

Teaching Hospital - Karapitiya

Galle, Southern Province, Sri Lanka

Lady Ridgeway Hospital for Children

Colombo, Western Province, Sri Lanka

Colombo South Teaching Hospital

Kalubowila, Western Province, Sri Lanka

Colombo North Teaching Hospital

Ragama, Western Province, Sri Lanka

Countries

Sri Lanka

Other Identifiers

EC-24-125

Identifier Type: -

Identifier Source: org_study_id

U1111-1318-1599

Identifier Type: OTHER

Identifier Source: secondary_id