Does Short-Term Anti-Seizure Prophylaxis After Traumatic Brain Injury Decrease Seizure Rates?

The primary objective of this study is to prospectively assess in randomized fashion whether short term anti-seizure prophylaxis in traumatic brain injured patients decreases the incidence of seizures in the early post-injury period. A secondary objective is to evaluate whether there are differences in mortality, hospital length of stay, functional outcome at hospital discharge, hospital cost, discharge status (home, rehabilitation facility, etc.) for patients who receive and do not receive anti-seizure prophylaxis.

Study Overview

• Status: Unknown
• Conditions: Seizures; Traumatic Brain Injury
• Intervention / Treatment: Drug: Levetiracetam

Detailed Description

The efficacy of anti-seizure prophylaxis in head injury patients remains controversial. Current recommendations for the use of anti-seizure prophylaxis are based upon a single institution study that has not been reproduced with other studies contradicting their conclusions. The proposed study will be a randomized prospective study at Loyola University Medical Center to assess the efficacy of anti-seizure prophylaxis in patients who have suffered traumatic brain injury (TBI). Patients with suspected TBI will undergo computed tomographic (CT) scan of the head. Following identification of TBI on CT scan, patients will be randomized to one of two study groups. Patients will be randomized to receive a seven-day course of anti-seizure prophylaxis with levetiracetam (UCB Pharma Inc.; Keppra) or randomized to a study group that will not receive anti-seizure prophylaxis. Patients will be consented prior to entry in the study. Patients will be followed for a total of seven days post injury for clinical signs of seizure activity. Additionally, patients will be assessed at one month post injury for clinical signs of seizure activity.

• Study Type: Interventional
• Enrollment (Anticipated): 2300
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Richard P Gonzalez, MD; Phone Number: 708-327-2072; Email: richard.gonzalez@lumc.edu
• Study Contact Backup: Name: Michael Anstadt, MD; Phone Number: 708-327.2072; Email: manstadt@lumc.edu

Study Locations

• United States
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Recruiting
      • Loyola University Medical Center
      • Contact: Richard Gonzalez, MD; Phone Number: 708-327-2072; Email: richard.gonzalez@lumc.edu
      • Contact: Michael Anstadt, MD; Phone Number: 708-327-2706; Email: manstadt@lumc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients who have suffered intracranial injury identified by CT Scan

Exclusion Criteria:

• Age less than 18
• Pregnant patients
• Death in ED
• Seizure history or use of antiepileptic medication prior to admission
• Contraindication to study drug
• Any post-injury seizures prior to randomization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: No seizure prophylaxis; Participants randomized to this arm will not receive anti-seizure prophylaxis
EXPERIMENTAL: Seizure Prophylaxis; Participants randomized to this arm will receive the anti-seizure prophylaxis drug Levetiracetam for seven days post traumatic brain injury.	Drug: Levetiracetam; Participants assigned to the experimental arm will receive a seven day course of levetiracetam for post-traumatic brain injury; Other Names: Keppra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seizures (count of seizures)	For all patients, the count of seizures will be recorded and compared between the two arms	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	For all patients, days from head injury to death or last follow-up will be recorded and compared between the two arms.	30 days

Collaborators and Investigators

• Sponsor: Loyola University
• Investigators: Principal Investigator: Richard Gonzalez, MD, Loyola University

Publications and helpful links

General Publications

• Pitkanen A, Immonen R. Epilepsy related to traumatic brain injury. Neurotherapeutics. 2014 Apr;11(2):286-96. doi: 10.1007/s13311-014-0260-7.
• Torbic H, Forni AA, Anger KE, Degrado JR, Greenwood BC. Antiepileptics for seizure prophylaxis after traumatic brain injury. Am J Health Syst Pharm. 2013 Dec 1;70(23):2064, 2067. doi: 10.2146/ajhp130439. No abstract available.
• Cranley MR, Craner M, McGilloway E. Antiepileptic prophylaxis following severe traumatic brain injury within a military cohort. J R Army Med Corps. 2016 Apr;162(2):109-14. doi: 10.1136/jramc-2014-000392. Epub 2015 Feb 24.
• Temkin NR, Dikmen SS, Wilensky AJ, Keihm J, Chabal S, Winn HR. A randomized, double-blind study of phenytoin for the prevention of post-traumatic seizures. N Engl J Med. 1990 Aug 23;323(8):497-502. doi: 10.1056/NEJM199008233230801.
• Young B, Rapp RP, Norton JA, Haack D, Walsh JW. Failure of prophylactically administered phenytoin to prevent post-traumatic seizures in children. Childs Brain. 1983;10(3):185-92. doi: 10.1159/000120113.
• Bhullar IS, Johnson D, Paul JP, Kerwin AJ, Tepas JJ 3rd, Frykberg ER. More harm than good: antiseizure prophylaxis after traumatic brain injury does not decrease seizure rates but may inhibit functional recovery. J Trauma Acute Care Surg. 2014 Jan;76(1):54-60; discussion 60-1. doi: 10.1097/TA.0b013e3182aafd15.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2017
• Primary Completion (ANTICIPATED): April 1, 2020
• Study Completion (ANTICIPATED): April 1, 2021

Study Registration Dates

• First Submitted: February 13, 2017
• First Submitted That Met QC Criteria: February 14, 2017
• First Posted (ACTUAL): February 15, 2017

Study Record Updates

• Last Update Posted (ACTUAL): August 6, 2019
• Last Update Submitted That Met QC Criteria: August 5, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Prophylaxis; Seizures; Traumatic Brain Injury; Levetiracetam
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic; Seizures; Anticonvulsants; Nootropic Agents; Levetiracetam
• Other Study ID Numbers: 209136

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share individual participant data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No