Prophylactic Anti-epileptic Regimen in Traumatic Brain Injury

Official title

Role of Prophylactic Anti-epileptic Regimen in Traumatic Brain Injury

Overview

To evaluate the effectiveness and safety of anti-epileptic drugs in the prevention of early and late post-traumatic seizures among patients with trauma brain injury

Detailed description

Traumatic brain injury (TBI) is one of the leading causes of death and disabilities worldwide. It has been estimated that 64-74 million individuals experience TBI from all causes each year. According to the Centers for Disease Control and Prevention (CDC), an estimated 1.7 million people sustain a TBI every year in the USA.

TBI can be associated with chronic consequences such as physical and psychological disorders. In 2021, there were over 69,000 deaths because of TBI in the USA, with about 190 TBI-related deaths every day. The risk of having a TBI is highest among adolescents, young adults, and older people.

Post-traumatic seizures can be classified into immediate, that is, occurring within the first 24 hours; early, occurring within 1-7 days of life; and late, if seizures occur after 7 days of life. Prophylactic use of anti-epileptic drugs during the first 7 days is protective against early seizures. A lower incidence of seizures was observed in patients who received anti-epileptic prophylaxis. The current guidelines for post-TBI seizure prophylaxis emphasise the effectiveness of seizure control, and phenytoin and levetiracetam are frequently prescribed.

Levetiracetam is a new antiepileptic drug that is used for prophylaxis in post-traumatic brain injury. Levetiracetam has low plasma protein binding and a lower risk of drug interactions and adverse events. Levetiracetam's major metabolic pathway is hydrolysis, not via CYP450. However, the drug is eliminated via the kidneys, so patients who are critically ill or suffer from renal insufficiency may require dosage adjustment. Therapeutic drug monitoring may be required in complicated cases. A few side effects associated with levetiracetam include headache, nausea, vomiting, drowsiness, dizziness, and behavioural changes.

Although current guidelines recommend levetiracetam for post-TBI seizure prophylaxis, there is no available data regarding its effectiveness outcomes at Assiut University Trauma Hospital. This highlights the need for a local clinical evaluation to assess prescribing practices and patient outcomes in this setting. Therefore, this study aimed to evaluate the effectiveness of anti-epileptic drugs compared with the control group in preventing early and late post-traumatic seizures in patients with TBI at Assiut University Trauma Hospital.

Interventions

• Drug Anti-Epileptic
  The anti-epileptic drugs will take three months

Primary outcome measures

• Incidence of seizure [Time frame: 3 months]

Secondary outcome measures (3)

• Assess neurological outcomes [Time frame: during the 3 months]
• Assess in-hospital mortality rates [Time frame: During hospitalization (assessed up to 7 days)]]
• Escalation of anti-epileptic therapy [Time frame: During the 3 months]

Eligibility criteria

Inclusion criteria

• Patients with a confirmed diagnosis of traumatic brain injury (clinical and/or radiological), including both surgical and conservative management
• Admission within 24 hours of injury
• Eligible for antiepileptic prophylaxis according to clinical guidelines
• Written informed consent obtained.

Exclusion criteria

• Pre-existing epilepsy or seizure disorder.
• Seizure episode before or during admission unrelated to acute TBI.
• Prior use of antiepileptic drugs before admission.
• Severe renal impairment (creatinine clearance <30 mL/min).
• Hepatic failure.
• Pregnancy or lactation.
• Known hypersensitivity to antiepileptic drugs

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Case-control

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Ng SY, Lee AYW. Traumatic Brain Injuries: Pathophysiology and Potential Therapeutic Targets. Front Cell Neurosci. 2019 Nov 27;13:528. doi: 10.3389/fncel.2019.00528. eCollection 2019. PMID 31827423
• Dewan MC, Rattani A, Gupta S, Baticulon RE, Hung YC, Punchak M, Agrawal A, Adeleye AO, Shrime MG, Rubiano AM, Rosenfeld JV, Park KB. Estimating the global incidence of traumatic brain injury. J Neurosurg. 2018 Apr 27;130(4):1080-1097. doi: 10.3171/2017.10.JNS17352. Print 2019 Apr 1. PMID 29701556
• Faul M, Wald MM, Xu L, Coronado VG. Traumatic brain injury in the United States: emergency department visits, hospitalizations, and deaths, 2002-2006. 2010.
• Stocchetti N, Zanier ER. Chronic impact of traumatic brain injury on outcome and quality of life: a narrative review. Crit Care. 2016 Jun 21;20(1):148. doi: 10.1186/s13054-016-1318-1. PMID 27323708
• Centers for Disease Control and Prevention. National center for health statistics: mortality data on CDC WONDER. https://wonder.cdc.gov/mcd.html 2026.
• Bruns J Jr, Hauser WA. The epidemiology of traumatic brain injury: a review. Epilepsia. 2003;44(s10):2-10. doi: 10.1046/j.1528-1157.44.s10.3.x. PMID 14511388
• han A, Muntaha ST, Ayaz H, Tariq A, Mughal H. Use Of Anti-Epileptics For Seizure Prophylaxis After Traumatic Brain Injury In The Pediatric Population. Journal of Rawalpindi Medical College. 2024;28(4).
• Khan SA, Bhatti SN, Khan AA, Khan Afridi EA, Muhammad G, Gul N, Zadran KK, Alam S, Aurangzeb A. Comparison Of Efficacy Of Phenytoin And Levetiracetam For Prevention Of Early Post Traumatic Seizures. J Ayub Med Coll Abbottabad. 2016 Jul-Sep;28(3):455-460. PMID 28712212

Identifiers

NCT: NCT07535736 · 2026

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗