Preventing early seizures after traumatic brain injury

Assessing Phenytoin and Levetiracetam Efficacy, Cost-Effectiveness, and CYP2C9/SV2A Polymorphism in Early Post-Traumatic Seizures: A Multicentric Prospective Randomized Trial

This randomized study will test whether phenytoin, levetiracetam, or placebo best prevent early seizures in people hospitalized with moderate-to-severe traumatic brain injury.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 1260 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: All India Institute of Medical Sciences, Jodhpur (other gov)
• Locations: 3 sites (Chandigarh, Punjab and 2 other locations)
• Trial ID: NCT07072624 on ClinicalTrials.gov

What this trial studies

This is a multicenter, randomized Phase 4 trial that assigns participants to phenytoin, levetiracetam, or placebo to prevent early post-traumatic seizures. The study will also analyze genetic polymorphisms to see whether drug response or seizure risk is affected by patient genetics. Primary outcomes include seizure incidence in the early post-injury period, with secondary outcomes of clinical and functional recovery, safety, and cost-effectiveness. Eligible patients include those with severe blunt TBI (GCS <10), CT-evidence of intracranial injury with higher GCS, or penetrating injuries, while exclusions include pregnancy, prior anticonvulsant use, pre-enrollment seizures, or devastating injury with imminent brain death.

Who should consider this trial

Good fit: Ideal candidates are people admitted soon after moderate-to-severe TBI (for example GCS <10 or CT evidence of intracranial injury) who are not already on anticonvulsants and are not pregnant.

Not a fit: Patients who already had seizures before enrollment, are already taking anticonvulsants, are pregnant, or have devastating injuries expected to cause imminent brain death are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the trial could identify the safest and most effective drug to prevent early post-traumatic seizures and help improve recovery after TBI.

How similar studies have performed: Previous research is limited and mixed—older trials suggested some benefit with phenytoin but high-quality head-to-head randomized data and studies incorporating genetics are largely lacking.

Eligibility criteria

Inclusion Criteria:

1. Patients of severe blunt TBI with GCS score less than 10.
2. Patients with GCS of more than 10 in the presence of computed tomographic imaging findings consistent with brain injury: subarachnoid hemorrhage \[SAH\], subdural hematoma \[SDH\], epidural hematoma \[EDH\], intracerebral hemorrhage \[ICH\], or diffuse axonal injury \[DAI\], depressed skull fracture.
3. Patients with penetrating injury.

Exclusion Criteria:

1. Females of childbearing age with urine pregnancy test positive.
2. Devastating brain injury with expected or confirmed brain death within 48 hours of hospital admission,
3. Prehospital use of anticonvulsants
4. Development of seizures before enrolment.

Where this trial is running

Chandigarh, Punjab and 2 other locations

• Postgraduate Institute of Medical Education & Research — Chandigarh, Punjab, India (RECRUITING)
• AIIMS Jodhpur — Jodhpur, Rajasthan, India (RECRUITING)
• Sanjay Gandhi Postgraduate Institute of Medical Sciences — Lucknow, Uttar Pradesh, India (RECRUITING)

Study contacts

• Principal investigator: Dr Apinderpreet Singh Additional Professor, MCh Neurosugery — Post Graduate Institute of Medical Education and Research, Chandigarh
• Study coordinator: Dr Jaskaran Singh Gosal Associate Professor, MCh Neurosurgery

Conditions: Seizures, Traumatic Brain Injuries, Traumatic Brain Injury Patients, Post Traumatic Seizures, Early Post Traumatic Seizures, Traumatic Brain Injury, Seizure Prophylaxis, Antiepileptic drugs