INTRODUCTION
Traumatic brain injury is a major public health challenge in India, contributing significantly to morbidity and mortality, primarily due to road traffic accidents, falls, and occupational injuries. With an estimated incidence of 150–200 cases per 100,000 population annually, Traumatic brain injury imposes a substantial burden on India’s healthcare system, particularly in resource-constrained settings. One of the critical complications of Traumatic brain injury is post-traumatic seizures , which can occur early within 7 days or late beyond 7 days, increasing the risk of secondary brain injury, prolonged hospitalisation, and poor functional outcomes. Seizure prophylaxis with anti-epileptic drugs is a standard practice to mitigate this risk, particularly in patients with moderate to severe traumatic brain injury Glasgow Coma Scale is less then or equal to 12.
Phenytoin has been the cornerstone of seizure prophylaxis in Traumatic brain injury for decades, valued for its efficacy, widespread availability, and low cost. However, its use is limited by a complex pharmacokinetic profile, requiring therapeutic drug monitoring and a higher incidence of adverse effects such as rash, hepatotoxicity, and neurotoxicity. These challenges are particularly pronounced in the Indian population, where pharmacogenetics variations, such as the higher prevalence of CYP2C93 polymorphisms, can lead to altered phenytoin metabolism, increasing toxicity risks.
Levetiracetam, a newer anti-epileptic drugs, has emerged as a promising alternative due to its favourable safety profile, minimal drug interactions, and simpler dosing regimen, which does not require Therapeutic drug monitoring. However, its higher cost and limited availability in some Indian settings pose barriers to widespread adoption.
AIMS AND OBJECTIVES
Aims: Comparison of Efficacy, Safety, and Clinical Outcomes of Phenytoin versus Levetiracetam for Seizure Prophylaxis in patients with Traumatic Brain Injury in neurosurgery department at J.A Group of hospitals , Gajra Raja Medical College, Gwalior.
Objectives
Primary
· To compare Efficacy and Safety of Phenytoin vs Levetiracetam to address seizure prevention.
· To compare Clinical Outcomes of Phenytoin vs Levetiracetam based on hospital stay, ICU stay, mortality.
Secondary
· Cost effectiveness between phenytoin vs Levetiracetam.
MATERIAL AND METHODS
Study Design
· Type: Prospective, observational, comparative study.
Study Setting
· Trauma unit and Neurosurgery department of J.A Group of hospitals of Gajra Raja Medical College, Gwalior.
Study Population
· Participants: Patients diagnosed with moderate to severe Traumatic brain injury Glasgow Coma Scale is less then or equal to 12 is prescribed either phenytoin or levetiracetam for seizure prophylaxis.
Study Duration
12 months
Sample Size
From the article Shahbaz et al. 2016: with a significance level of 1% and considering drop out rate of 15%, the calculated sample size of the study came out to be 40 in 1 group; therefore a total sample of 80 patients.
Calculation
P1=Proportion of efficacy in Phenytoin group =94.8%=0.948
P2=Proportion of efficacy in Levetiracetam group= 45.5%=0.455
P =(P1 + P2)/2 =0.7015
Z1-a/2 = 2.576 at 1% significance level
Z1-b = 2.326 power of test at 99%
n(sample size) =35.5~36
Assuming 15% drop out rate, sample size calculation 35.5+5.3=40.8 ~ 40
There for, each group 40 sample will taken
Methodology
The following methodology is designed for a prospective, observational, comparative study of phenytoin vs levetiracetam for seizure prophylaxis in patients with traumatic brain injury. The study includes follow-up at 1week, 1st month and 3rd month, post-traumatic brain injury, focusing on the Indian population.
Recruitment and Enrollment:
· Process: Patients will be enrolled from trauma unit or neurosurgery ward within 24 hours of Traumatic brain injury diagnosis. Treating physicians’ prescriptions (phenytoin or levetiracetam) will determine group allocation, reflecting real-world practice.
· Prescribed standard doses of phenytoin (e.g., 15-20 mg/kg loading dose, 100 mg TID maintenance) or levetiracetam (e.g., 500 mg BID, IV or oral) is to be given to the patients.
· Detailed history of mechanism of injury (e.g., road traffic accident, fall), CT/MRI findings (e.g., contusion, hematoma), co-morbidities (e.g., diabetes, hypertension), seizure occurrence, duration and frequency (number of times of seizure occurrence), nose-ear bleed, past diseases and medication history will be taken.
· GCS score will be noted.
Inclusion Criteria
· Patients diagnosed with Acute Traumatic Brain Injury patients diagnosed (confirmed by clinical assessment and/or CT/MRI).
· Patients diagnosed with moderate to severe TBI (GCS less then or equal to12).
· Patients willing to signed written consent.
Exclusion Criteria
· Penetrating head injuries (due to different seizure risk profiles).
· Pre-existing seizures, epilepsy or neurological disorders requiring AEDs.
· Patients Contraindicated to phenytoin or levetiracetam (e.g., hypersensitivity, severe hepatic/renal impairment).
· Patients transferred to other facilities.
· Pregnant and lactating women.
Follow-Up Data:
First Follow-Up (7 Days Post-Traumatic Brain Injury):
· Seizure occurrence (clinical or EEG-confirmed, if available).
· Adverse effects (e.g., rash, dizziness, hypotension, neurotoxicity etc.) assessed via patient/caregiver reports and medical records.
· Hospital/ICU status (discharged, in ICU, or ward).
Second Follow-Up (1 Month Post-Traumatic Brain Injury):
· Seizure occurrence.
· Adverse effects and their resolution or persistence.
· Length of hospital stay and ICU stay (in days).
Third Follow-Up (3 Month Post-Traumatic Brain Injury):
· Seizure occurrence.
· Adverse effects and their resolution or persistence.
· Length of hospital stay and ICU stay (in days).
OBSERVATION TABLE
Patients Characterises
| | Phenytoin | Levetiracetam |
| GENDER DISTRIBUTION 1.Male 2.Female 3.Other | | |
| GCS (?/15) E?V?M? | | |
| SEVERITY OF INJURY 1.Moderate 2.Severe | | |
| TYPES OF TRAUMA 1.Road traffic accident 2.Fall 3.Assault | | |
Seizures Incidence (Efficacy)
| Group | Seizure occurrence in 1week | Seizure occurrence in 1 month | Seizure Occurrence in 3 months |
| | Yes | No | Yes | No | Yes | No |
| Phenytoin | | | |
| Levetiracetam | | | |
| | | | | | |
Scale /scoring for seizure incidence: binary (seizure occurred if Yes:1, No:0)
Seizure frequency (Efficacy)
| Group | Number of seizure occurred at 1week | Number of seizure occurred at 1month | Number of seizure occurred at 3month |
| Phenytoin | | | |
| Levetiracetam | | | |
Scale/scoring for seizure frequency: continuous variable (eg. 0,1,2,3,…. per patient)
Adverse drug events (safety)
| No | Adverse Events | Phenytoin | Levetiracetam |
| 1 | Nausea | | |
| 2 | Vomiting | | |
| 3 | Rash | | |
| 4 | Itching | | |
| 5 | Headache | | |
| 6 | Excessive sleepiness | | |
| 7 | Behavioural changes | | |
| 8 | Hypotension | | |
| 9 | Dizziness | | |
| 10 | Ataxia | | |
Cost Effectiveness
| | Cost at 1week | Cost at 1month | Cost at 3month |
| Phenytoin | | | |
| Levetiracetam | | | |
Clinical outcome
| | Total Number of day stay in hospital | Number of day stay in ICU | Number of stay in Ward | Mortality |
| Phenytoin | | | | |
| Levetiracetam | | | | |
Statistical Analysis
· Statistical Analysis will be carried out by using SPSS 23 software. Presentation of categorical variables was done in form of number and percentage. Quantitative data were presented as mean, standard deviation. Assessment of data within the group is carried out by Student’s paired t-test and between the groups of patients of traumatic brain injury receiving phenytoin and levetiracetam by unpaired t-test.
· P value less then 0.05 will be considered statistically significant.