Pharmacological Management of Seizures Post Traumatic Brain Injury

Official title

Pharmacological Management of Seizures Post Traumatic Brain Injury (MAST)

Overview

The overall aim of the MAST trial is to define best practice in the use of anti-epileptic drugs (AEDs) for patients following a traumatic brain injury (TBI). The trial will consist of two parts. The first part aims to answer whether a shorter or a longer course of AEDs is better to prevent further seizures in patients who have started having seizures following TBI (MAST - duration). The second part aims to answer whether a 7-day course of either Phenytoin or Levetiracetam should be used for patients with a serious TBI to prevent seizures from starting (MAST- prophylaxis).

Detailed description

The majority of patients who suffer a traumatic brain injury (TBI) do not need to stay in hospital overnight. However, some require admission to a specialist hospital, as their injury is more serious. Seizures can be harmful or even fatal, if not treated appropriately. Medications that reduce the risk of seizures are called antiepileptic drugs (AEDs). However, AEDs have side effects, which can affect patients' quality of life, memory, concentration and general health.

Patients with seizures after TBI are typically prescribed an AED to prevent further seizures, most commonly Phenytoin or Levetiracetam. Some doctors favour a short course, whereas others favour a longer course. The first part of the trial aims to answer if one approach is better than the other (MAST-duration). The second part of the trial aims to answer if a 7-day course of either Phenytoin or Levetiracetam should be used for patients with a serious TBI to prevent seizures from happening (MAST- prophylaxis).

All patients admitted to a neurosurgical unit (NSU) within the UK, with a serious TBI, will be considered for the trial. Patients who have been started on either Phenytoin or Levetiracteam by their clinical team due to seizures will be randomised to either up to 3 months or at least 6 months of treatment. In an independent, parallel trial, TBI patients who have not had a seizure will be randomised to phenytoin, levetiracetam or no treatment. All patients will be managed as per usual NHS practice and followed up for 24 months.

Interventions

• Drug Phenytoin Sodium
  Dosing will be as prescribed clinically by the treating physician. Phenytoin Sodium may be administered orally, intravenously or via nasogastric tube.
• Drug Levetiracetam
  Dosing will be as prescribed clinically by the treating physician.Levetiracetam may be administered orally, intravenously or via nasogastric tube.

Primary outcome measures

• MAST-DURATION: Occurrence of late PTS [Time frame: Within 24 months post traumatic brain injury]
• MAST-PROPHYLAXIS: Occurrence of PTS [Time frame: Within 2 weeks post TBI]

Secondary outcome measures (10)

• MAST-PROPHYLAXIS: Occurrence of post-traumatic seizures [Time frame: Within 24 months post traumatic brain injury]
• MAST-PROPHYLAXIS: Time to post-traumatic seizure [Time frame: Within 24 months post traumatic brain injury]
• Both trials: Disability [Time frame: At 6, 12, 18 and 24 months]
• Both trials: Cognitive function [Time frame: At 6, 12, 18 and 24 months]
• Both trials: Quality of life [Time frame: At 6, 12, 18 and 24 months]
• Both trials: Adverse events [Time frame: At 6, 12, 18 and 24 months]
• Both trials: Hospital admissions [Time frame: Within 24 months post traumatic brain injury]
• Both trials: Frequency of PTS [Time frame: Within 24 months post traumatic brain injury]
• Both trials: Mortality [Time frame: At 6, 12, 18 and 24 months]
• Both trials: Frequency of adverse events of special interest [Time frame: Up to 24 months]

Eligibility criteria

MAST DURATION

Inclusion criteria

• Patients aged ≥10 years with TBI managed in an NSU who have started on an phenytoin or levetiracetam due to an acute symptomatic seizure during acute hospitalisation
• Patient or Legal Representative is willing and able to provide informed consent or in the absence of a legal representative, an Independent Healthcare Professional provides authorisation for patient enrolment

Exclusion criteria

• Unsurvivable injury
• Previous history of epilepsy
• Patients who are on an AED pre-TBI
• Patient who has been clinically prescribed an AED other than phenytoin or levetiracetam
• Unwillingness to take products containing gelatin (animal products)
• Severe lactose intolerance or any known hypersensitivity to study drug or any of its excipients

MAST-PROPHYLAXIS

Inclusion criteria

• Patients aged ≥10 years, with TBI managed in an NSU without an acute symptomatic seizure
• Patient or Legal Representative is willing and able to provide informed consent or in the absence of a legal representative, an Independent Healthcare Professional provides authorisation for patient enrolment within 48 hours of admittance.

Exclusion criteria

• Post-traumatic seizures
• Unsurvivable injury
• Previous history of epilepsy
• Patients who are on an AED pre-TBI
• Pregnancy or breastfeeding
• Unwillingness to take products containing gelatin (animal products)
• Severe lactose intolerance or any known hypersensitivity to study drug or any of its excipients
• Time interval from the time of admission to NSU to randomisation exceeds 48 hours

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

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT04573803 · A095460

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗