A Phase 4 interventional study of Phenobarbital and Levetiracetam in Neonatal Seizures and HIE - Hypoxic - Ischemic Encephalopathy, sponsored by Mansoura University. Not yet recruiting at 2 sites in Egypt. Open to participants aged 1 Day to 30 Days. Per ClinicalTrials.gov, last updated 2025-12-16.
Sponsored by Mansoura University · Phase 4, Interventional, and Treatment
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
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.
Mansoura University is the lead sponsor of 1,077 studies on the registry; 183 are open to participants now.
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Exclusion Criteria:
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
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
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
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 has emerged as an alternative Anti-seizure medication that may offer improved safety and tolerability profiles.
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.
Time frame: 24-hour seizure-free period.
Comparison of the effectiveness of anti-seizure medications for 48 continuous hours after the start 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.
Time frame: 48 hours after initiation of treatment
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Mansoura University