Treatment of Seizures in Neonate With HIE

NCT ID: NCT07284498

Last Updated: 2025-12-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE4

Total Enrollment

66 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-01-01

Study Completion Date

2026-10-31

Brief Summary

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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

Detailed Description

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This research will be conducted as a randomized controlled open-labeled single-centered clinical trial. The Declaration of Helsinki will guide the study's conduct. Informed consents will be obtained from neonates' parents, and the local ethical committee approval is mandatory.

Baseline data as detailed medical history, physical examination, gestational age, postnatal age, birth weight, APGAR score at 5 and 10 minutes. Laboratory parameter (complete blood cell count, electrolytes, serum creatinine, liver enzymes, and blood gas), respiratory assessment (need for oxygen and respiratory support), cardiac assessment including (blood pressure/ heart rate), type of feeding, head ultrasound.

The enrolled patients will be classified into three groups: Phenobarbital group (intervention group A), Levetiracetam standard dose group (intervention group B), Levetiracetam high dose group (intervention group C).

Patients in Group A (intervention group I) will receive phenobarbital at a loading dose of 20 mg/kg within a 20-minute time frame from the start of seizures. If the seizures doesn't stopped after 20 minutes, another 20 mg/kg of the same medication will be added, and if the seizures doesn't stopped within the total time frame of 40 minutes, this will be considered a treatment failure.

While patients in Group B (Intervention Group II) as well as Group C (Control Group) will receive levetiracetam at a loading dose of 30 mg/kg and 60 mg/kg respectively. Within a timeframe of 20 minutes from the start of seizures, If the seizures doesn't stopped. The same beginning dose will be repeated for both groups, in case of seizures doesn't stopped 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.

For all groups, if the first line of treatment fails, phenytoin will be considered as the second line treatment for treating seizures, and a dose of (20 mg/kg diluted in 20 ml of saline solution over 20 minutes) will be started. If the seizures is not controlled, the third line will be midazolam, given as a continuous infusion.

Evaluations will include patients who will be followed up during the study period by measuring the following parameters: frequent episodes of seizure/ time to stop seizures, EEG finding, follow-up head ultrasound (US) and brain magnetic resonance imaging (MRI) (if the neonate-stable), blood pressure/ heart rate (need for inotrope/vasopressor treatment), respiratory status (need for oxygen and respiratory support), feeding intolerance (vomiting); and changes in laboratory parameters (complete blood cell count to assess anemia, electrolytes, serum creatinine, liver enzymes, ammonia, and arterial blood gas (ABG) analysis or any significant side effects that were attributed to an anti-seizures medication by the clinical team and will be recorded in the medical record.

Conditions

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Neonatal Seizures HIE - Hypoxic - Ischemic Encephalopathy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phenobarbital Arm ( Group A )

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.

Group Type ACTIVE_COMPARATOR

Phenobarbital

Intervention Type 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

Levetiracetam Standard Dose Arm ( Group B )

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.

Group Type ACTIVE_COMPARATOR

Levetiracetam

Intervention Type DRUG

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

Levetiracetam High Dose Arm ( Group C )

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.

Group Type ACTIVE_COMPARATOR

Levetiracetam

Intervention Type DRUG

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

Interventions

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Phenobarbital

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

Intervention Type DRUG

Levetiracetam

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

1. Exclusive metabolic causes.
2. Serum creatinine greater than 1.6 mg/dl.
3. Known pyridoxine-dependent seizures.
4. Prior treatment with anti-epileptic drugs.
Minimum Eligible Age

1 Day

Maximum Eligible Age

30 Days

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mansoura University

OTHER

Sponsor Role lead

Responsible Party

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Abdulwahab Uosef Alqarni, M.Sc

Mansoura University, PhD student

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Moetaza Soliman, Associate Professor

Role: PRINCIPAL_INVESTIGATOR

Faculty of Pharmacy, Mansoura University

Nada Abdelfattah, Associate Professor

Role: PRINCIPAL_INVESTIGATOR

University Children's Hospital, Mansoura University

Locations

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University Children's Hospital, Mansoura University

Al Mansurah, , Egypt

Site Status

Al Galaa Teaching Hospital

Cairo, , Egypt

Site Status

Countries

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Egypt

Central Contacts

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Abdulwahab Alqarni

Role: CONTACT

+966533655255

Mustafa Sharaf EL-Deen, Lecturer of Clinical Pharmacy

Role: CONTACT

+201140102401

References

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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.

Reference Type RESULT
PMID: 15791116 (View on PubMed)

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.

Reference Type RESULT
PMID: 987769 (View on PubMed)

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.

Reference Type RESULT
PMID: 35673948 (View on PubMed)

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.

Reference Type RESULT
PMID: 34867732 (View on PubMed)

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.

Reference Type RESULT
PMID: 36823477 (View on PubMed)

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.

Reference Type RESULT
PMID: 35311411 (View on PubMed)

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

Reference Type 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.

Reference Type RESULT
PMID: 36401982 (View on PubMed)

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.

Reference Type RESULT
PMID: 32385134 (View on PubMed)

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.

Reference Type RESULT
PMID: 34124790 (View on PubMed)

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.

Reference Type RESULT
PMID: 36578326 (View on PubMed)

Other Identifiers

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MDP.25.01.179

Identifier Type: -

Identifier Source: org_study_id