Levetiracetam Versus Phenobarbitone for the Treatment of Neonatal Seizures in a Tertiary Care Hospital.

NCT07401433 | Completed

• 1 other identifier: DHQ-DIK-IREB NO. 4806
• Study Type: interventional
• Target: 260
• Locations: 1 country
• Sites: 1

Brief Summary

Neonatal seizures are a common neurological emergency in newborn babies and can lead to serious brain injury if not treated promptly. Phenobarbitone is commonly used as first-line treatment, but it is associated with delayed seizure control and adverse effects such as sedation and poor feeding. This study was conducted to compare the effectiveness and safety of levetiracetam with conventional antiepileptic drugs (phenobarbitone with or without phenytoin) in the treatment of neonatal seizures. In this randomized controlled trial, newborns aged 0 to 28 days diagnosed with seizures were randomly assigned to receive either intravenous levetiracetam or phenobarbitone-based therapy. The main outcomes assessed were seizure control within 40 minutes, seizure freedom at 24 and 48 hours, recurrence of seizures, time taken to control seizures, adverse effects, and mortality. The results of this study aim to provide evidence on whether levetiracetam is a safer and more effective alternative for managing neonatal seizures in a tertiary care hospital setting.

Conditions

Neonatal Seizures

Keywords

Neonatal seizures; Levetiracetam; Phenobarbitone; Antiepileptic drugs; Neonatal intensive care

Outcome Measures

Primary Outcomes (1)

• Seizure Cessation Within 40 Minutes

  Proportion of neonates with clinically diagnosed seizures whose seizures stopped completely within 40 minutes after administration of the first-line anticonvulsant.

  Immediately after first-line drug administration (within 40 minutes)

Secondary Outcomes (5)

• Time to Seizure Cessation

  From first-line drug administration to seizure cessation (up to 40 minutes)

• Need for Second-Line Anticonvulsant

  Immediately after first-line treatment failure (within 40 minutes of initial drug administration)

• Seizure Recurrence During Hospital Stay

  From initial seizure control through 7 days of hospitalization

• Incidence of Adverse Drug Reactions

  From first drug administration through the first 5 days of hospitalization

• Mortality

  From enrollment through assessment at discharge, 28 days and 90days

Study Arms (2)

Levitiracetam Group

EXPERIMENTAL

Neonates presenting with clinically diagnosed seizures will receive intravenous levetiracetam as the first-line anticonvulsant. Initial dose 20 mg/kg IV, followed by 20 mg/kg IV after 12 hours if seizures persist. Maintenance dose will be 10 mg/kg IV/PO twice daily as per hospital protocol. Seizure control and side effects will be monitored.

Drug: Levetiracetam

Phenobarbitone Group

ACTIVE COMPARATOR

Neonates with clinically diagnosed seizures received intravenous phenobarbitone as the first-line anticonvulsant with a loading dose of 20 mg/kg followed by maintenance dosing of 3-5 mg/kg/day. In cases of persistent seizures, phenytoin was added according to standard dosing protocols. Seizure response and adverse effects were monitored.

Drug: Phenobarbital Sodium Injection

Interventions

Levetiracetam DRUG

Neonates with clinically diagnosed seizures received intravenous levetiracetam as the first-line anticonvulsant. Levetiracetam was administered at a rate of 1 mg/kg/min followed by a loading dose of 20 mg/kg diluted in normal saline. Maintenance therapy of 20 mg/kg/day was continued after seizure control. Seizure response and adverse effects were monitored.

Levitiracetam Group

Phenobarbital Sodium Injection DRUG

Phenobarbitone will be administered intravenously as the first-line anticonvulsant for neonatal seizures. Initial loading dose 20 mg/kg IV. If seizures persist after 20 minutes, a second dose of 10 mg/kg IV will be given. Maintenance dose of 5 mg/kg IV/PO once daily will be continued until seizure control is achieved or until discharge. Seizure response and adverse effects will be monitored.

Phenobarbitone Group

Eligibility Criteria

• Age: 1 Day - 28 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Neonates (0-28 days old) with clinically diagnosed seizures.
• Both term and preterm neonates.
• Admitted to the neonatal intensive care unit (NICU) or pediatric ward.
• Written informed consent obtained from parents or legal guardians.

You may not qualify if:

• Neonates with major congenital anomalies or genetic syndromes.
• Neonates with severe renal or hepatic impairment.
• Neonates with metabolic disorders requiring specific treatment (e.g., hypoglycemia, hypocalcemia) unless seizures persist after correction.
• Neonates already receiving anticonvulsant therapy prior to admission.
• Neonates with confirmed meningitis or central nervous system infections requiring specific management (unless seizures persist after appropriate treatment).
• Neonates with life-threatening conditions where study treatment cannot be safely administered.
• Parents or legal guardians refusing consent.

Sponsors & Collaborators

• Hayat Abad Medical Complex, Peshawar: lead
• Gomal Medical College: collaborator

Study Sites (1)

Gomal Medical College

Dera Ismāīl Khān, KPK, 29111, Pakistan

Location

Related Publications (9)

• İşgüder R, Güzel O, Ağın H, Yılmaz Ü, Akarcan SE, Çelik T, et al. - Efficacy and Safety of IV Levetiracetam in Children With Acute Repetitive Seizures. Pediatric Neurology. 2014 Nov;51(5):688-95.

  RESULT

• Khan O, Cipriani C, Wright C, Crisp E, Kirmani B - Role of intravenous levetiracetam for acute seizure management in preterm neonates. Pediatr Neurol. 2013 Nov;49(5):340-3.

  RESULT

• Sourbron J, Chan H, Heijden EAW van der, Klarenbeek P, Wijnen BFM, Haan GJ de, et al. - Review on the relevance of therapeutic drug monitoring of levetiracetam. Seizure - European Journal of Epilepsy. 2018 Nov;62:131-5.

  RESULT

• Efficacy of levetiracetam as the first line antiepileptic drug in neonatal seizures (ResearchGate PDF).

  RESULT

• Sharpe C, Reiner GE, Davis SL, Nespeca M, Gold JJ, Rasmussen M, et al. - Levetiracetam Versus Phenobarbital for Neonatal Seizures: A Randomized Controlled Trial. Pediatrics. 2020 Jun;145(6):e20193182.

  RESULT

• McHugh DC, Lancaster S, Manganas LN - A Systematic Review of the Efficacy of Levetiracetam in Neonatal Seizures. Neuropediatrics. 2018 Feb;49(1):12-7.

  RESULT

• Weldegerima K, Gebremariam DS, Haftu H, Berhe G, Hadgu A, Mohammedamin MM - Neonatal Seizure Pattern, Outcome, and its Predictors Among Neonates Admitted to NICU of Ayder Comprehensive Specialized Hospital, Mekelle, Tigray, Ethiopia. Int J Gen Med. 2023;16:4343-55.

  RESULT

• Kaminiow K, Kozak S, Paprocka J. Neonatal Seizures Revisited. Children (Basel). 2021 Feb 18;8(2):155. doi: 10.3390/children8020155.

  PMID: 33670692 RESULT

• Ramantani G, Schmitt B, Plecko B, Pressler RM, Wohlrab G, Klebermass-Schrehof K, Hagmann C, Pisani F, Boylan GB. Neonatal Seizures-Are We there Yet? Neuropediatrics. 2019 Oct;50(5):280-293. doi: 10.1055/s-0039-1693149. Epub 2019 Jul 24.

  PMID: 31340400 RESULT

MeSH Terms

Interventions

Levetiracetam; Phenobarbital

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Barbiturates; Pyrimidinones; Pyrimidines

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, treating clinicians, investigators, and outcome assessors were blinded to treatment allocation. Randomization was performed using sealed opaque envelopes to maintain allocation concealment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Trainee Registrar

Model Details: Participants were randomly assigned to one of two parallel treatment groups: intravenous levetiracetam or phenobarbitone-based therapy, with no crossover between groups.

Study Record Dates

• First Submitted: January 17, 2026
• First Posted: February 10, 2026
• Study Start: April 8, 2024
• Primary Completion: March 31, 2025
• Study Completion: April 10, 2025
• Last Updated: February 10, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1)