Efficacy Of Levetiracetam in the Treatment of Neonatal Seizures Presenting at Tertiary Care Hospital.
Phase: NA
Conditions: Neonatal Seizures
Sponsor: Hayat Abad Medical Complex, Peshawar

STUDY PROTOCOL 
1. Study Title 
Levetiracetam Versus Phenobarbitone for the Treatment of Neonatal Seizures in 
a Tertiary Care Hospital 
Short title/acronyms: Levetiracetam Versus Phenobarbitone for the Treatment of Neonatal Seizures 
2. Protocol ID 
DHQ-DIK-IREB NO. 4806 
Date: 26 February 2024. 
ClinicalTrials.gov Identifier: NCT Not Yet Assigned 
3. Background & Rationale 
Neonatal seizures are the most common neurological emergency in neonates and are associated with 
significant morbidity and mortality. Phenobarbitone has traditionally been the first-line anticonvulsant; 
however, its efficacy is limited and it has significant adverse effects. Levetiracetam is emerging as a safer 
alternative with promising seizure control rates. This study aims to compare the efficacy and safety of 
levetiracetam versus phenobarbitone in neonates with seizures. 
4. Objectives 
Primary Objective 
To compare seizure control rates within 24 hours between levetiracetam and phenobarbitone in neonates 
with clinically diagnosed seizures. 
Secondary Objectives 
• 
To compare time to seizure cessation between both drugs. 
• 
To compare the need for second-line anticonvulsant therapy. 
• 
To compare seizure recurrence during hospital stay. 
• 
To compare adverse drug reactions. 
• 
To compare mortality rates. 
5. Study Design 
A prospective randomized controlled trial conducted at the Neonatal Intensive Care Unit (NICU) and 
Pediatric wards of a tertiary care hospital. 
6. Study Setting 
Neonatal Intensive Care Unit (NICU) and Pediatric ward at [Your Hospital Name], Pakistan. 

7. Study Population 
Neonates (0–28 days) with clinically diagnosed seizures admitted to NICU or Pediatric ward. 
8. Sample Size 
Based on previous literature, assuming seizure control rates of 70% with levetiracetam and 50% with 
phenobarbitone, with 80% power and 5% significance level, the calculated sample size is n = 100 (50 in 
each group). However we will include all the patients accepting the inclusion criteria during one year of 
study. 
9. Inclusion Criteria 
• 
Neonates (0–28 days old) with clinically diagnosed seizures. 
• 
Term and preterm neonates. 
• 
Parents/legal guardians provide informed consent. 
10. Exclusion Criteria 
• 
Major congenital anomalies or genetic syndromes. 
• 
Severe renal or hepatic impairment. 
• 
Neonates already receiving anticonvulsants before admission. 
• 
Neonates with metabolic seizures not responding after correction. 
• 
Neonates with CNS infection requiring specific treatment (unless seizures persist). 
• 
Parents refuse consent. 
11. Intervention 
Arm A: Levetiracetam 
• 
Loading dose: 20 mg/kg IV 
• 
Repeat dose: 20 mg/kg IV after 12 hours if seizures persist 
• 
Maintenance dose: 10 mg/kg IV/PO twice daily until seizure control or discharge 
Arm B: Phenobarbitone 
• 
Loading dose: 20 mg/kg IV 
• 
Repeat dose: 10 mg/kg IV after 20 minutes if seizures persist 
• 
Maintenance dose: 5 mg/kg IV/PO once daily until seizure control or discharge 
12. Outcome Measures 
Primary Outcome 
Seizure control rate within 24 hours after first-line treatment. 

Secondary Outcomes 
• 
Time to seizure cessation 
• 
Need for second-line anticonvulsant 
• 
Seizure recurrence during hospital stays 
• 
Adverse drug reactions 
• 
Mortality during hospital stay 
13. Study Procedures 
1. Neonates with clinical seizures will be assessed by pediatric/neonatology team. 
2. Eligible neonates will be randomized into either levetiracetam or phenobarbitone group. 
3. Baseline data including demographic details, gestational age, birth weight, and clinical status will 
be recorded. 
4. Standard investigations will be done (CBC, blood glucose, electrolytes, ABG, neuroimaging if 
required). 
5. Treatment will be administered as per group allocation. 
6. Monitoring of seizure activity and side effects will be done for 72 hours and until discharge. 
7. Data will be recorded on a structured proforma. 
14. Randomization 
Simple randomization using Lottery method. 
15. Data Collection 
Data will be collected on a structured proforma and entered into SPSS version 25. 
16. Ethical Considerations 
Approval will be obtained from the Institutional Review Board (IRB). Informed consent will be obtained 
from parents/legal guardians. 
17. Principal Investigator: 
Dr. Gohar Ali