Levetiracetam Versus Phenobarbital in Benzodiazepines Unresponsive Paediatric Prolonged Seizures

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

Interventions

DRUG

Levetiracetam IV

Leveget injection 500mg/5ml

DRUG

Phenobarbital

Phenobarbital injection 200mg/ml (BPI Insein)

Sponsors & Collaborators

• Ministry of Health and Sports, Myanmar

  lead OTHER_GOV

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

1 Month

Max Age

12 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-07-22

Primary Completion

2026-03-28

Completion

2026-06-30

Countries

• Burma

Study Locations