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

Sponsor
Kullasate Sakpichaisakul (Other)
Overall Status
Recruiting
CT.gov ID
NCT04302116
Collaborator
(none)
250
1
2
78.5
3.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Combination therapy with vigabatrin and prednisolone
  • Drug: Vigabatrin Tablets
N/A

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 Design

Study Type:
Interventional
Anticipated Enrollment :
250 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
A pragmatic parallel group randomised trial comparing vigabatrin with high dose prednisolone to vigabatrin treatment alone in the treatment of infantile spasm.A pragmatic parallel group randomised trial comparing vigabatrin with high dose prednisolone to vigabatrin treatment alone in the treatment of infantile spasm.
Masking:
Double (Investigator, Outcomes Assessor)
Masking Description:
Each patient will visit the clinic at Day 8, 14, 43, and 3 months by outcome assessor who is blinded for treatment to determine seizure frequency and adverse events. Those patients will be seen and under taking care of primary neurologists and pharmacists who are not blinded to treatment at the same visit as a standard clinical practice and check with compliance and adjust vigabatrin or prednisolone following each treatment allocated (if needed). Family or caregivers will not be blinded to treatment. EEG will be scored using BASED scores at Day 0 (before treatment), 14, and 43 to assess the resolution of hypsarrhythmia.
Primary Purpose:
Treatment
Official Title:
Efficacy of Vigabatrin With High Dose Prednisolone Combination Therapy Versus Vigabatrin Alone for Infantile Spasm: a Randomized Trial
Actual Study Start Date :
May 18, 2020
Anticipated Primary Completion Date :
Jun 1, 2026
Anticipated Study Completion Date :
Dec 1, 2026

Arms and Interventions

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
  • Outcome Measures

    Primary Outcome Measures

    1. Cessation of spasms [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.

    Secondary Outcome Measures

    1. Electrographic response [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.

    2. Electroclinical response [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.

    3. Extended electroclinical response [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.

    4. The time taken to absence of spasms [Day 1 to Day 14]

      Duration for clinical cessation of spasms after initiation treatment

    5. Relapse of spasms [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.

    6. Adverse reactions [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.

    7. Epilepsy outcome at age 18 months [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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    2 Months to 14 Months
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Queen Sirikit National Institute of Child Health Ratchathewi Bangkok Thailand 10400

    Sponsors and Collaborators

    • Kullasate Sakpichaisakul

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Kullasate Sakpichaisakul, Pediatric epileptologist, Queen Sirikit National Institute of Child Health
    ClinicalTrials.gov Identifier:
    NCT04302116
    Other Study ID Numbers:
    • QSNICH63-008
    First Posted:
    Mar 10, 2020
    Last Update Posted:
    Aug 25, 2021
    Last Verified:
    Aug 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Kullasate Sakpichaisakul, Pediatric epileptologist, Queen Sirikit National Institute of Child Health
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 25, 2021