Levetiracetam Versus Phenobarbital in Benzodiazepines Unresponsive Paediatric Prolonged Seizures

NCT07098728 | Recruiting DMC

• 2 other identifiers: 55/UM1,REC.2024Research and Ethics Committee
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 2

Brief Summary

Convulsive prolonged seizures in children are the most common life-threatening neurological emergencies. The aim of active management of seizure control is to prevent irreversible neuronal damage as early as possible. Although there is evidence of the use of benzodiazepines as the initial management for prolonged seizures, up to a third of patients do not respond to benzodiazepines. Many trials study the rate of seizures control among various second-line antiseizure medications (ASMs) in benzodiazepines unresponsive convulsive prolonged seizures. However, there is still few recommendations for paediatric population which drug is the most effective to control seizures rapidly and there is also a limited data on which drug has less adverse effects and is well tolerated. Currently, injection phenobarbital or levetiracetam is used as second-line antiseizure medication based on expert opinion in many centres globally including Yangon Children's Hospital. From this study, it is expected to identify the safer and more effective second-line treatment for prolonged seizures in children and be helpful in considering the alternative choice of appropriate medications in the management of prolonged seizures to include in the local guideline. A hospital-based randomized comparative study will be conducted at Yangon Children's Hospital. All children with benzodiazepines unresponsive prolonged seizures will be eligible for this study with the minimum sample size of 180 (90:90). Consecutive sample collection by block randomization will be done throughout the study period. The informed consent will be taken after explanation of nature, purposes, procedure, durations, benefits and risks. This study will be started with the approval of Academic Board of Study and Research and Ethics Committee, University of Medicine 1, Yangon. By this study, clinical response of intravenous levetiracetam versus intravenous phenobarbital in children with benzodiazepines unresponsive prolonged seizures will be evaluated. Aim of this study is to study the clinical response of intravenous levetiracetam versus intravenous phenobarbital in children with prolonged seizures unresponsive to benzodiazepines. Findings will support the choice of the safer and more effective second-line treatment for prolonged seizures in Myanmar children. After case selection according to inclusion criteria and getting informed consent, computerized block randomization will be done. Total 9 blocks will be generated with group A and group B. Each child will be assigned as group A or group B according to randomization. All patients will be received supportive care according to treatment guideline of the ward. Group A patients will be treated with intravenous levetiracetam 40 mg/kg (maximum of 3000 mg) over 15 minutes. Group B patients will be treated with intravenous phenobarbital 20 mg/kg (maximum of 1000 mg) over 20 minutes. Injection levetiracetam will be diluted with 5% dextrose water to a concentration of 50 mg/ml. Injection phenobarbital will be diluted to become 20 ml with 5% dextrose water. All participants will also be monitored for oxygen saturation, respiratory rate and pattern, pulse rate, pulse volume, and blood pressure to detect treatment-related adverse effects. Monitoring will be conducted before, during, and 5 minutes after the assigned drug infusion, then hourly for 4 hours, every 2 hours for the following 4 hours, and every 4 hours thereafter. The primary outcome of the study will be the clinical cessation of the seizure at five minutes after the completion of the infusion of intravenous levetiracetam or phenobarbital. The secondary outcome of the study will be the recurrence of seizure within 12 hours after the commencement of the study medications, need of other medications for active seizure control within 12 hours after the commencement of the study medications, need for rapid sequence induction (RSI) with thiopentone for on-going seizure management after administration of study medications. These secondary outcomes will be assessed in treatment-responsive groups. Treatment related adverse effects will also be assessed within five minutes of drug infusion in both treatment groups and within 12 hours in treatment-responsive groups. Data analysis will be done to compare the clinical response. If the patient's seizure has stopped five minutes after completing the infusion of the assigned medication, a maintenance dose of either levetiracetam or phenobarbital, whichever was previously used, will be administered intravenously. If the patient is still experiencing seizure five minutes after completing the infusion of the assigned medication, the patient will be treated with an alternative second-line ASM. If the patient experiences serious treatment-related adverse effects within five minutes of the levetiracetam or phenobarbital infusion, the drug infusion will be stopped.

Conditions

Seizure

Keywords

Status Epilepticus

Outcome Measures

Primary Outcomes (1)

• Seizure control

  Clinical cessation of the seizure at five minutes after the completion of the infusion of intravenous levetiracetam or phenobarbital

  at five minutes after the completion of the infusion of intravenous levetiracetam or phenobarbital

Secondary Outcomes (4)

• Seizure recurrence

  within 12 hours after the commencement of the study medications in treatment-responsive group

• Need of other medications

  within 12 hours after the commencement of the study medications in treatment-responsive group

• Need for rapid sequence induction (RSI)

  after administration of study medications in treatment-responsive group

• Treatment-related adverse effects

  within five minutes of drug infusion in both treatment groups and within 12 hours in treatment-responsive groups

Study Arms (2)

Injection Levetiracetam Group

ACTIVE COMPARATOR

Injection Levetiracetam

Drug: Levetiracetam IV

Injection Phenobarbital Group

ACTIVE COMPARATOR

Injection Phenobarbital

Drug: Phenobarbital

Interventions

Levetiracetam IV DRUG

Leveget injection 500mg/5ml

Injection Levetiracetam Group

Phenobarbital DRUG

Phenobarbital injection 200mg/ml (BPI Insein)

Injection Phenobarbital Group

Eligibility Criteria

• Age: 1 Month - 12 Years
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Children aged between 1 month to 12 years with prolonged seizures who do not respond to any two bolus doses of benzodiazepines

You may not qualify if:

• Any of the following criteria will be excluded.
• Children who receive anticonvulsant treatment other than benzodiazepines for the acute management of prolonged seizures
• Acute symptomatic seizures due to hypertensive encephalopathy or hypoglycaemia
• Presence of arrythmia or respiratory depression
• Known case of chronic kidney disease or chronic liver disease

Sponsors & Collaborators

• Ministry of Health and Sports, Myanmar: lead

Study Sites (2)

Yangon Children's Hospital

Yangon, Yangon, Burma

RECRUITING

Yangon Children's Hospital

Yangon, Yangon, Burma

RECRUITING

MeSH Terms

Conditions

Seizures; Status Epilepticus

Interventions

Phenobarbital

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Barbiturates; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Paediatrician

Study Record Dates

• First Submitted: July 21, 2025
• First Posted: August 1, 2025
• Study Start: July 22, 2025
• Primary Completion: March 28, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: August 1, 2025

Record last verified: 2024-12

Locations

BU (2)