Treatment of Seizures in Neonate With HIE | NCT07284498

NCT07284498

Protocol Section

Identification Module

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Description Module

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.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
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

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
Comparison of the effectiveness of anti-seizure medications for 48 continuous hours after the start of treatment.	Sustained seizure cessation (48 h): Absence of clinical or electrographic seizures for ≥48 consecutive hours after antiseizure therapy. Unit: Yes/No Need for inotropes/vasopressors: Requirement for vasoactive agents (e.g., dopamine) for hypotension within 48 hours. Unit: Yes/No Respiratory support requirement: Need for supplemental oxygen or ventilatory support (CPAP/NIV/mechanical ventilation). Unit: Yes/No Feeding intolerance: Vomiting, abdominal distension, or interruption of enteral feeding. Unit: Yes/No Hematologic abnormalities: Anemia (Hb <13 g/dL), thrombocytopenia (platelets <150×10⁹/L), or leukopenia (WBC <5×10⁹/L). Unit: ×10³/µL Electrolyte disturbances: Abnormal Na, K, Ca, or glucose levels per neonatal reference ranges. Unit: mmol/L Acute liver injury: AST or ALT >2× age-adjusted upper limit. Unit: IU/L Hyperammonemia: Plasma ammonia >100 µmol/L. Unit: µmol/L Abnormal blood gas: Metabolic or respiratory acidosis: pH <7.25 and/or BE ≤ -10 mmol/L.

Eligibility Module

Contacts/Locations Module

Central Contacts

Name	Role	Phone	Extension	Email
Abdulwahab Alqarni	Contact	+966533655255		ph.abdulwahab@gmail.com
Mustafa Sharaf EL-Deen, Lecturer of Clinical Pharmacy	Contact	+201140102401		sharaf_eldeen@mans.edu.eg

Overall Officials

Name	Affiliation	Role
Moetaza Soliman, Associate Professor	Faculty of Pharmacy, Mansoura University	Principal Investigator
Nada Abdelfattah, Associate Professor	University Children's Hospital, Mansoura University	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University Children's Hospital, Mansoura University		Al Mansurah			Egypt
Al Galaa Teaching Hospital

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
15791116	Result	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.
987769	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.

ID	Term
D010634	Phenobarbital
D000077287	Levetiracetam

ID	Term
D001463	Barbiturates
D011744	Pyrimidinones
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring