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)

NCT06838559 | Active Not Recruiting Phase 4 DMC

• 2 other identifiers: EC-24-125U1111-1318-1599
• Study Type: interventional
• Target: 182
• Locations: 1 country
• Sites: 7

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. 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. 2.Does the duration of treatment (7 vs. 14 days) influence relapse rates and developmental outcomes in infants with IESS?
3. 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.
4. 4.Receive either a 7-day or 14-day course of oral prednisolone as part of their treatment
5. 5.Be monitored for spasm frequency and any side effects during hospital observation for the first 48 hours
6. 6.Maintain a spasm diary during the treatment period to track spasm frequency
7. 7.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

Conditions

Spasms, Infantile; Prednisolone

Keywords

Randomized controlled trial; Spasms, Infantile; Prednisolone; Infant; Electroencephalography; Child Development; Relapse; Tapering Regimen; Treatment Duration

Outcome Measures

Primary Outcomes (1)

• Electroclinical Remission at Day 14 and Day 28

  This primary outcome measure compares the efficacy of the 7-day versus 14-day oral prednisolone regimens. Electroclinical remission is defined as (1) spasm control-no clinically recognizable spasms for a minimum of 24 consecutive hours as recorded by the caregiver-and (2) EEG remission-disappearance of hypsarrhythmia with the BASED score improved to 3 or less on a standardized 30-minute sleep EEG (with 5 minutes of wakefulness).

  Assessed at 14 days and 28 days after treatment initiation.

Secondary Outcomes (4)

• Long-Term Spasm Control

  Assessed at 42 days, 3 months, 6 months, and 12 months post-treatment.

• Spasm Relapse Rate and Time to Relapse

  Evaluated continuously over the 12-month follow-up period.

• Developmental Outcome at 24 Months

  Assessed at 24 months following treatment initiation.

• Evolution of Epilepsy

  Assessed at 12 months post-treatment.

Study Arms (2)

treatment arm A

EXPERIMENTAL

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.

Drug: Short-Duration Oral Prednisolone with Extended Tapering

treatment arm B

ACTIVE COMPARATOR

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.

Drug: Standard Oral Prednisolone Regimen with Tapering

Interventions

Short-Duration Oral Prednisolone with Extended Tapering 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 A

Standard Oral Prednisolone Regimen with Tapering 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.

treatment arm B

Eligibility Criteria

• Age: 3 Months - 24 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colombo: lead

Study Sites (7)

Sirimavo Bandaranayake Specialized Children's Hospital

Peradeniya, Central Province, 20400, Sri Lanka

Location

Teaching Hospital Anuradhapura

Anuradhapura, North Central Province, 50000, Sri Lanka

Location

Teaching Hospital - Jaffna

Jaffna, Northern Province, 40000, Sri Lanka

Location

Teaching Hospital - Karapitiya

Galle, Southern Province, 80000, Sri Lanka

Location

Lady Ridgeway Hospital for Children

Colombo, Western Province, 00800, Sri Lanka

Location

Colombo South Teaching Hospital

Kalubowila, Western Province, 10350, Sri Lanka

Location

Colombo North Teaching Hospital

Ragama, Western Province, 11010, Sri Lanka

Location

MeSH Terms

Conditions

Spasms, Infantile; Recurrence

Condition Hierarchy (Ancestors)

Epilepsy, Generalized; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jithangi Wanigasinghe, MD, MPhil

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

  PRINCIPAL INVESTIGATOR

• Carukshi Arambepola, MSc, MD

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

  PRINCIPAL INVESTIGATOR

• Shalini Sri Ranganathan, MD, PhD

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

  PRINCIPAL INVESTIGATOR

• Nimesha Gamhewage, MD, DCH

  Department of Paediatrics, University of Sri Jayewardenepura, Sri Lanka

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Both the outcome assessor (MBBS-qualified research assistant) and the data analyst will be blinded to the treatment arms. By implementing these measures, the risk of bias is minimized, and the credibility of the study results is enhanced, ensuring that the conclusions drawn from the data are based solely on the observed effects of the treatments without any influence from knowledge of the treatment allocations.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor in Paediatric Neurology, Department of Paediatrics, Faculty of Medicine, University of Colombo, Sri Lanka

Model Details: Randomized (1:1), single-blinded, multi-centre, parallel-group clinical trial.

Study Record Dates

• First Submitted: February 17, 2025
• First Posted: February 20, 2025
• Study Start: January 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: February 24, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

SR (7)