MAST

Pharmacological Management of Seizures Post Traumatic Brain Injury

Research summary

The majority of patients who suffer a traumatic brain injury (TBI), from, for example, road accidents, falls, assaults or sports do not need to stay in hospital overnight. However, approximately 9,000 patients require admission to a specialist hospital each year in the UK, as their injury is more serious. Seizures are a significant complication of TBI. Seizures can be harmful and in the worst case fatal if not treated appropriately. Medications that reduce the risk of seizures are called antiepileptic drugs (AEDs). However, AEDs have side effects, which if severe, can affect patients' quality of life, memory, concentration and general health.

Patients with seizures after TBI are typically started on a course of AED to prevent further seizures. Some doctors favour a short course of AEDs, whereas others favour a longer course. The first part of the trial aims to answer if one approach is better than the other. The second part of the trial aims to answer if a 7-day course of an AED should be used for patients with a serious TBI to prevent seizures from happening. We recently undertook a survey and half of the doctors who replied favour this approach, while half do not (due to concerns about the side effects of AEDs).

The variation in the current practice of AED prescribing is due to the lack of high-quality evidence. The project comprises of two studies running side by side that will help to define best practice in the use of AEDs for patients with serious TBI. All patients admitted to a participating hospital with a serious TBI will be considered for the trial based on pre-specified criteria. Following consent, patients who have been started on an AED by their clinical team due to seizures will be randomly placed into one of two groups of study A. One group will continue receiving AED for up to 3 months, and the other for at least 6 months. Patients who have not had a seizure will be randomly placed into one of three groups of study B. One group will receive one type of AED for seven days (phenytoin), another will receive a second type of AED for seven days (levetiracetam), and the third group will not receive an AED. All patients will be managed as per usual NHS practice and followed up for 24 months. Outcome measures will focus on the occurrence of seizures, activities of daily living, memory, concentration, quality of life, and side effects. We will also undertake a health economic analysis. We will begin with a pilot phase (50 patients in study A and 130 in study B), and if the pilot is successful, we will roll out the substantive study across the NHS (total 428 patients in study A and 1221 in study B in 25 NSUs).

clinicaltrials.gov


Main inclusion criteria

MAST DURATION

  1. 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

  2. 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

MAST-PROPHYLAXIS

  1. Patients aged ≥10 years, with TBI managed in an NSU without an acute symptomatic seizure
  2. 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.

Main exclusion criteria

MAST DURATION

  1. Unsurvivable injury

  2. Previous history of epilepsy

  3. Patients who are on an AED pre-TBI

  4. Patient who has been clinically prescribed an AED other than phenytoin or levetiracetam

  5. Unwillingness to take products containing gelatin (animal products)

  6. Severe lactose intolerance or any known hypersensitivity to study drug or any of its excipients

MAST-PROPHYLAXIS

  1. Post-traumatic seizures

  2. Unsurvivable injury

  3. Previous history of epilepsy

  4. Patients who are on an AED pre-TBI

  5. Pregnancy or breastfeeding

  6. Unwillingness to take products containing gelatin (animal products)

  7. Severe lactose intolerance or any known hypersensitivity to study drug or any of its excipients

  8. Time interval from the time of admission to NSU to randomisation exceeds 48 hours



Chief investigator

Prof Peter Hutchinson

Contact details

Clinical Trials Coordinator: Samantha Lawes

Telephone: 01223 256624 | Email: samantha.lawes@addenbrookes.nhs.uk