Treatment of Seizures in Neonate With HIE

NCT07284498 | Not Yet Recruiting Phase 4

• 1 other identifier: MDP.25.01.179
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 2

Brief Summary

Aim of the study To evaluate and compare phenobarbital's and levetiracetam's safety and efficacy for treating seizures in neonates with moderate to severe HIE

Conditions

Neonatal Seizures; HIE - Hypoxic - Ischemic Encephalopathy

Keywords

Neonatal Seizure; HIE; Phenobarbital; Levetiracetam

Outcome Measures

Primary Outcomes (1)

• Comparison of findings anti-seizure Medication safety and efficacy

  A complete 24-hour seizure-free period is measured and assessed by clinical symptoms and/or an independent aEEG assessment of seizure-free within 20 to 40 minutes of initiating drug therapy, without the need for second-line antiepileptic therapy.

  24-hour seizure-free period.

Secondary Outcomes (1)

• Comparison of the effectiveness of anti-seizure medications for 48 continuous hours after the start of treatment.

  48 hours after initiation of treatment

Study Arms (3)

Phenobarbital Arm ( Group A )

ACTIVE COMPARATOR

Patients in Group A will receive PHENobarbital at a loading dose of 20 mg/kg within a 20-minute time frame from the start of treatment. If the seizure dose is not stopped after 20 minutes, another 20 mg/kg of the same medication will be added, and if the seizure dose is not stopped within the total time frame of 40 minutes, this will be considered a treatment failure. If seizures are controlled, patients will receive a maintenance dose of PHENobarbital 3-5 mg/kg/day IV/PO, in 1-2 divided doses, starting 12 hours after the loading dose.

Drug: Phenobarbital

Levetiracetam Standard Dose Arm ( Group B )

ACTIVE COMPARATOR

Patients in Group B will receive levETIRAcetam at a loading dose of 30 mg/kg within a timeframe of 20 minutes from the start of seizures if the seizures don't stop. The same beginning dose will be repeated, in case the seizures don't stop within the 40-minute time frame, which leads to the treatment being considered a failure and a need to move to the second line of treatment. If seizures are controlled, patients will receive maintenance dose of levETIRAcetam 30 mg/kg/day IV or orally, divided into three daily doses.

Drug: Levetiracetam

Levetiracetam High Dose Arm ( Group C )

ACTIVE COMPARATOR

Patients in Group C will receive levETIRAcetam at a loading dose of 60 mg/kg within a timeframe of 20 minutes from the start of seizures if the seizures don't stop. The same beginning dose will be repeated, in case the seizures don't stop within the 40-minute time frame, which leads to the treatment being considered a failure and a need to move to the second line of treatment. If seizures are controlled, patients will receive maintenance dose of levETIRAcetam 60 mg/kg/day IV or orally, divided into three daily doses.

Drug: Levetiracetam

Interventions

Phenobarbital DRUG

Phenobarbital is strongly recommended by the World Health Organization as the first-line treatment of neonatal seizures and is the standard of care at most institutions

Phenobarbital Arm ( Group A )

Levetiracetam DRUG

levetiracetam has emerged as an alternative Anti-seizure medication that may offer improved safety and tolerability profiles.

Levetiracetam High Dose Arm ( Group C ); Levetiracetam Standard Dose Arm ( Group B )

Eligibility Criteria

• Age: 1 Day - 30 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Neonates diagnosed with moderate or severe HIE.
• Presence of clinical seizures (focal / generalized tonic /colonic, myoclonic, subtle and spasms) and/or documented amplitude electroencephalogram (aEEG) abnormality within the first 72 hours.

You may not qualify if:

• Exclusive metabolic causes.
• Serum creatinine greater than 1.6 mg/dl.
• Known pyridoxine-dependent seizures.
• Prior treatment with anti-epileptic drugs.

Sponsors & Collaborators

• Mansoura University: lead

Study Sites (2)

University Children's Hospital, Mansoura University

Al Mansurah, Egypt

Location

Al Galaa Teaching Hospital

Cairo, Egypt

Location

Related Publications (11)

• Finster M, Wood M. The Apgar score has survived the test of time. Anesthesiology. 2005 Apr;102(4):855-7. doi: 10.1097/00000542-200504000-00022.

  PMID: 15791116 RESULT

• Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol. 1976 Oct;33(10):696-705. doi: 10.1001/archneur.1976.00500100030012.

  PMID: 987769 RESULT

• Susnerwala S, Joshi A, Deshmukh L, Londhe A. Levetiracetam or Phenobarbitone as a First-Line Anticonvulsant in Asphyxiated Term Newborns? An Open-Label, Single-Center, Randomized, Controlled, Pragmatic Trial. Hosp Pediatr. 2022 Jul 1;12(7):647-653. doi: 10.1542/hpeds.2021-006415.

  PMID: 35673948 RESULT

• Qiao MY, Cui HT, Zhao LZ, Miao JK, Chen QX. Efficacy and Safety of Levetiracetam vs. Phenobarbital for Neonatal Seizures: A Systematic Review and Meta-Analysis. Front Neurol. 2021 Nov 18;12:747745. doi: 10.3389/fneur.2021.747745. eCollection 2021.

  PMID: 34867732 RESULT

• Gyandeep G, Behura SS, Sahu SK, Panda SK. Comparison between Phenobarbitone and Levetiracetam as the initial anticonvulsant in preterm neonatal seizures - a pilot randomized control trial in developing country setup. Eur J Pediatr. 2023 May;182(5):2133-2138. doi: 10.1007/s00431-023-04864-x. Epub 2023 Feb 24.

  PMID: 36823477 RESULT

• Verwoerd C, Limjoco J, Rajamanickam V, Knox A. Efficacy of Levetiracetam and Phenobarbital as First-Line Treatment for Neonatal Seizures. J Child Neurol. 2022 Apr;37(5):401-409. doi: 10.1177/08830738221086107. Epub 2022 Mar 20.

  PMID: 35311411 RESULT

• Efficacy of levetiracetam as the first line anti- epileptic drug in management of neonatal seizures

  RESULT

• Battig L, Dunner C, Cserpan D, Ruegger A, Hagmann C, Schmitt B, Pisani F, Ramantani G. Levetiracetam versus Phenobarbital for Neonatal Seizures: A Retrospective Cohort Study. Pediatr Neurol. 2023 Jan;138:62-70. doi: 10.1016/j.pediatrneurol.2022.10.004. Epub 2022 Oct 22.

  PMID: 36401982 RESULT

• Sharpe C, Reiner GE, Davis SL, Nespeca M, Gold JJ, Rasmussen M, Kuperman R, Harbert MJ, Michelson D, Joe P, Wang S, Rismanchi N, Le NM, Mower A, Kim J, Battin MR, Lane B, Honold J, Knodel E, Arnell K, Bridge R, Lee L, Ernstrom K, Raman R, Haas RH; NEOLEV2 INVESTIGATORS. Levetiracetam Versus Phenobarbital for Neonatal Seizures: A Randomized Controlled Trial. Pediatrics. 2020 Jun;145(6):e20193182. doi: 10.1542/peds.2019-3182. Epub 2020 May 8.

  PMID: 32385134 RESULT

• Hooper RG, Ramaswamy VV, Wahid RM, Satodia P, Bhulani A. Levetiracetam as the first-line treatment for neonatal seizures: a systematic review and meta-analysis. Dev Med Child Neurol. 2021 Nov;63(11):1283-1293. doi: 10.1111/dmcn.14943. Epub 2021 Jun 13.

  PMID: 34124790 RESULT

• Akeel NE, Suliman HA, Al-Shokary AH, Ibrahim AO, Kamal NM, Abdelgalil AA, Elmala MK, Elshorbagy HH, Nasef KA, Attia AM, Fathallah MGED. A Comparative Study of Levetiracetam and Phenobarbital for Neonatal Seizures as a First Line Treatment. Glob Pediatr Health. 2022 Dec 20;9:2333794X221143572. doi: 10.1177/2333794X221143572. eCollection 2022.

  PMID: 36578326 RESULT

MeSH Terms

Interventions

Phenobarbital; Levetiracetam

Intervention Hierarchy (Ancestors)

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

Study Officials

• Moetaza Soliman, Associate Professor

  Faculty of Pharmacy, Mansoura University

  PRINCIPAL INVESTIGATOR

• Nada Abdelfattah, Associate Professor

  University Children's Hospital, Mansoura University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Abdulwahab Alqarni

CONTACT

+966533655255; ph.abdulwahab@gmail.com

Mustafa Sharaf EL-Deen, Lecturer of Clinical Pharmacy

CONTACT

+201140102401; sharaf_eldeen@mans.edu.eg

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Mansoura University, PhD student

Study Record Dates

• First Submitted: November 16, 2025
• First Posted: December 16, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: December 16, 2025

Record last verified: 2025-12

Locations

EG (2)