Treatment of Seizures in Neonate With HIE (HIE)

December 2, 2025 updated by: Abdulwahab Uosef Alqarni, M.Sc, Mansoura University

Treatment of Seizures in Neonate With Hypoxic Ischemic Encephalopathy

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

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

66

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Egypt
      • Al Mansurah, Egypt
        • University Children's Hospital, Mansoura University
      • Cairo, Egypt
        • Al Galaa Teaching Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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.
Drug: 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
Active Comparator: 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.
Drug: Levetiracetam
levetiracetam has emerged as an alternative Anti-seizure medication that may offer improved safety and tolerability profiles.
Active Comparator: 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.
Drug: Levetiracetam
levetiracetam has emerged as an alternative Anti-seizure medication that may offer improved safety and tolerability profiles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison of findings anti-seizure Medication safety and efficacy
Time Frame: 24-hour seizure-free period.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison of the effectiveness of anti-seizure medications for 48 continuous hours after the start of treatment.
Time Frame: 48 hours after initiation of treatment

  1. Sustained seizure cessation (48 h):

    Absence of clinical or electrographic seizures for ≥48 consecutive hours after antiseizure therapy.

    Unit: Yes/No

  2. Need for inotropes/vasopressors:

    Requirement for vasoactive agents (e.g., dopamine) for hypotension within 48 hours.

    Unit: Yes/No

  3. Respiratory support requirement: Need for supplemental oxygen or ventilatory support (CPAP/NIV/mechanical ventilation).

    Unit: Yes/No

  4. Feeding intolerance:

    Vomiting, abdominal distension, or interruption of enteral feeding. Unit: Yes/No

  5. Hematologic abnormalities:

    Anemia (Hb <13 g/dL), thrombocytopenia (platelets <150×10⁹/L), or leukopenia (WBC <5×10⁹/L).

    Unit: ×10³/µL

  6. Electrolyte disturbances:

    Abnormal Na, K, Ca, or glucose levels per neonatal reference ranges. Unit: mmol/L

  7. Acute liver injury:

    AST or ALT >2× age-adjusted upper limit. Unit: IU/L

  8. Hyperammonemia:

    Plasma ammonia >100 µmol/L. Unit: µmol/L

  9. Abnormal blood gas:

Metabolic or respiratory acidosis: pH <7.25 and/or BE ≤ -10 mmol/L.
48 hours after initiation of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mansoura University

Investigators

  • Principal Investigator: Moetaza Soliman, Associate Professor, Faculty of pharmacy, Mansoura university
  • Principal Investigator: Nada Abdelfattah, Associate Professor, University Children's Hospital, Mansoura University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 1, 2026

Primary Completion (Estimated)

September 1, 2026

Study Completion (Estimated)

October 1, 2026

Study Registration Dates

First Submitted

November 16, 2025

First Submitted That Met QC Criteria

December 2, 2025

First Posted (Actual)

December 16, 2025

Study Record Updates

Last Update Posted (Actual)

December 16, 2025

Last Update Submitted That Met QC Criteria

December 2, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MDP.25.01.179

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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