Early Post-Traumatic Seizures Prevention Trial (E-PTS Trial)

All India Institute of Medical Sciences, Jodhpur

Status and phase: Enrolling; Phase 4

Conditions: Traumatic Brain Injury (TBI) Patients; Seizures; Traumatic Brain Injuries

Treatments: Drug: Levetiracetam; Drug: Phenytoin; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT07072624

AIIMS/IEC/2024/4889

IIRPIG-2023-0001210 (Other Grant/Funding Number)

Details and patient eligibility

About

Rationale/gaps in existing knowledge: The prophylaxis for post-traumatic seizures (PTS) remains controversial due to a lack of class I evidence. Investigators plan to conduct a high-quality, prospective, multicentric, randomized study regarding seizure prophylaxis in traumatic brain injury (TBI) with phenytoin, levetiracetam, and the placebo in three respective treatment groups, along with the effect of drug polymorphism on seizure occurrence.

Novelty: Literature is scarce regarding the ideal management of early PTS in traumatic brain injury (TBI), a major public health problem. Further, no study has evaluated the effect of genetic polymorphism on seizure occurrence in traumatic brain injury. This Multicentric study will be the first of its kind, not only in India but also globally.

Objectives: To evaluate the seizure incidence & efficacy of the respective anti-epileptic drug in each treatment arm. Assessment of clinical & functional outcomes, safety profile, and cost-effectiveness in each group. Effect of genetic polymorphisms on seizure incidence among study participants Methods: A Multicentric prospective randomized placebo-controlled double-blinded clinical trial is planned. After satisfying eligibility criteria and informed consent, TBI patients will be randomly allocated into three arms 'phenytoin arm', 'levetiracetam arm', and 'placebo'. Drug polymorphism will be analyzed in all the patients using quantitative real-time PCR.

Expected outcome: This study will provide high-quality evidence in PTS management and will establish the role of prophylactic anti-epileptics in PTS. This study also opens the plethora of undesignated roles of genetic polymorphism in the efficacy and safety of levetiracetam and phenytoin in traumatic brain injury patients.

Enrollment: 1,260 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1,260 participants in 3 patient groups, including a placebo group

Phenytoin

Active Comparator group

Treatment:

Drug: Phenytoin

Levetiracetam

Experimental group

Treatment:

Drug: Levetiracetam

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo