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

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ClinicalTrials.gov Identifier: NCT04302116
Recruitment Status : Recruiting
First Posted : March 10, 2020
Last Update Posted : August 25, 2021
Sponsor:
Information provided by (Responsible Party):
Kullasate Sakpichaisakul, Queen Sirikit National Institute of Child Health

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
Infantile Spasm West Syndrome Drug: Combination therapy with vigabatrin and prednisolone Drug: Vigabatrin Tablets Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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.
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
Estimated Primary Completion Date : June 2026
Estimated Study Completion Date : December 2026


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 Name: 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 Name: Sabril




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. The time taken to absence of spasms [ Time Frame: Day 1 to Day 14 ]
    Duration for clinical cessation of spasms after initiation treatment

  5. 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.

  6. 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.

  7. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   2 Months to 14 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04302116


Contacts
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Contact: Kullasate Sakpichaisakul, MD 66-2-354-8333 kullasate.s@rsu.ac.th
Contact: Sirorat Suwannachote, MD 66-2-354-8333 sirorat.s@rsu.ac.th

Locations
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Thailand
Queen Sirikit National Institute of Child Health Recruiting
Ratchathewi, Bangkok, Thailand, 10400
Contact: Kullasate Sakpichaisakul, MD       kullasate.s@rsu.ac.th   
Contact: Kantapon Trongkamolchai, MD       kantapon260619870@gmail.com   
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         
Sponsors and Collaborators
Kullasate Sakpichaisakul
Investigators
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Principal Investigator: Kullasate Sakpichaisakul, MD Queen Sirikit National Institute of Child Health
Additional Information:
Publications of Results:

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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: March 10, 2020    Key Record Dates
Last Update Posted: August 25, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is not a plan to make IPD available for the confidentiality.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Kullasate Sakpichaisakul, Queen Sirikit National Institute of Child Health:
Infantile Spasm
Vigabatrin
Prednisolone
Treatment
West Syndrome
Additional relevant MeSH terms:
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Muscle Cramp
Spasm
Spasms, Infantile
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Muscular Diseases
Musculoskeletal Diseases
Epilepsy, Generalized
Epilepsy
Brain Diseases
Central Nervous System Diseases
Epileptic Syndromes
Prednisolone
Methylprednisolone Acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone acetate
Vigabatrin
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antiemetics
Autonomic Agents