Treatment of Seizures in Neonate With HIE
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Phenobarbital, Levetiracetam.
- Who it may be relevant to
- Registry conditions: Neonatal Seizures, HIE - Hypoxic - Ischemic Encephalopathy. Basic parameters: 1 Day — 30 Days · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Egypt
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
Treatment of Seizures in Neonate With Hypoxic Ischemic Encephalopathy
Overview
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
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.
Interventions
- 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 - Drug Levetiracetam
levetiracetam has emerged as an alternative Anti-seizure medication that may offer improved safety and tolerability profiles.
Primary outcome measures
- Comparison of findings anti-seizure Medication safety and efficacy [Time frame: 24-hour seizure-free period.]
Secondary outcome measures (1)
- 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]
Eligibility criteria
Inclusion criteria
- 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.
Exclusion criteria
- Exclusive metabolic causes.
- Serum creatinine greater than 1.6 mg/dl.
- Known pyridoxine-dependent seizures.
- Prior treatment with anti-epileptic drugs.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Egypt · 2 centers
- University Children's Hospital, Mansoura University — Al Mansurah
- Al Galaa Teaching Hospital — Cairo
Publications
- 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
- 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
- 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
- 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
- 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
- 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
- Efficacy of levetiracetam as the first line anti- epileptic drug in management of neonatal seizures
- 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
Identifiers
NCT: NCT07284498 · MDP.25.01.179