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

August 24, 2021 updated by: Kullasate Sakpichaisakul

Efficacy of Vigabatrin With High Dose Prednisolone Combination Therapy Versus Vigabatrin Alone for Infantile Spasm: a Randomized Trial

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Anticipated)

250

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Thailand
    • Bangkok
      • Ratchathewi, Bangkok, Thailand, 10400
        • Recruiting
        • Queen Sirikit National Institute of Child Health
        • Contact:
        • Contact:
        • Principal Investigator:
          • Kullasate Sakpichaisakul, MD
        • Sub-Investigator:
          • Kantapon Trongkamolchai, MD
        • Sub-Investigator:
          • Somjit Sri-udomkajorn, MD
        • Sub-Investigator:
          • Sirorat Suwannachote, MD
        • Sub-Investigator:
          • Ravivan Wittawassamrankul, R Ph
        • Sub-Investigator:
          • Ravindra Arya, MD, DM

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 months to 1 year (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Combination therapy with vigabatrin and prednisolone

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.
Drug: Combination therapy with vigabatrin and prednisolone
High dose prednisolone (40 - 60 mg/day) for 1 month combined with vigabatrin treatment (50-150 mg/kg/day) twice daily for 4 months
Other Names:
  • Sabril with prednisolone
Active Comparator: Vigabatrin alone

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.
Drug: Vigabatrin Tablets
Vigabatrin (50-150 mg/kg/day) twice daily for 4 months
Other Names:
  • Sabril

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cessation of spasms
Time Frame: Assessed during Day 14 to Day 42 after treatment.
Defined as no witnessed spasms (either clusters or single spasms) from Day 14 to Day 42 inclusive.
Assessed during Day 14 to Day 42 after treatment.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Electrographic response
Time Frame: Assessed during Day 14 and Day 43 after treatment.
Disappearance of hypsarrhythmia defined by Burden of Amplitudes and Epileptiform Discharges (BASED) scoring system < 2 at Day 14 and Day 43 after treatment.
Assessed during Day 14 and Day 43 after treatment.
Electroclinical response
Time Frame: Between Day 14 and Day 21.
the cessation of spasms with the addition of absence of hypsarrhythmia (BASED score < 2) on the Day 14 EEG. Valid Day 14 EEGs will be undertaken between Day 14 and Day 21 inclusive.
Between Day 14 and Day 21.
Extended electroclinical response
Time Frame: Between Day 42 and Day 49.
Electroclinical response with the addition of absence of hypsarrhythmia (BASED score < 2) on the Day 42 EEG. Valid Day 42 EEGs will be undertaken between Day 42 and Day 49 inclusive.
Between Day 42 and Day 49.
The time taken to absence of spasms
Time Frame: Day 1 to Day 14
Duration for clinical cessation of spasms after initiation treatment
Day 1 to Day 14
Relapse of spasms
Time Frame: Day 42 to 3 months after treatment
Defined when a cluster of more than one spasm in reported after Day 42. No EEG is required.
Day 42 to 3 months after treatment
Adverse reactions
Time Frame: Day 1 to Day 14, from Day 15 to Day 42, and from Day 43 to 4 months into the trial
Each adverse event will be evaluated by the principal investigator to determine whether in their view it is an adverse reaction. If considered an adverse reaction, it will be reported by using the standard classification.
Day 1 to Day 14, from Day 15 to Day 42, and from Day 43 to 4 months into the trial
Epilepsy outcome at age 18 months
Time Frame: From Day 42 to age 18 months
Epilepsy status and antiepileptic drugs (AEDs) will be recorded by using the following categories: 1) Infantile spasms (clusters of spasms), 2) Any other epileptic seizure including febrile seizures, and 3) Names of any preventive AEDs prescribed
From Day 42 to age 18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kullasate Sakpichaisakul

Investigators

  • Principal Investigator: Kullasate Sakpichaisakul, MD, Queen Sirikit National Institute of Child Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 18, 2020

Primary Completion (Anticipated)

June 1, 2026

Study Completion (Anticipated)

December 1, 2026

Study Registration Dates

First Submitted

March 5, 2020

First Submitted That Met QC Criteria

March 6, 2020

First Posted (Actual)

March 10, 2020

Study Record Updates

Last Update Posted (Actual)

August 25, 2021

Last Update Submitted That Met QC Criteria

August 24, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • QSNICH63-008

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

There is not a plan to make IPD available for the confidentiality.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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