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).
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
1,649
Dosing will be as prescribed clinically by the treating physician. Phenytoin Sodium may be administered orally, intravenously or via nasogastric tube.
Dosing will be as prescribed clinically by the treating physician.Levetiracetam may be administered orally, intravenously or via nasogastric tube.
MAST-DURATION: Occurrence of late PTS
The primary outcome for MAST-DURATION is the occurrence of late post-traumatic seizure. This will be assessed by follow-up questionnaire.
Time frame: Within 24 months post traumatic brain injury
MAST-PROPHYLAXIS: Occurrence of PTS
The primary outcome for MAST-PROPHYLAXIS is the occurrence of an acute symptomatic seizure. This will be assessed in the neurosurgical unit, or by telephone following discharge.
Time frame: Within 2 weeks post TBI
MAST-PROPHYLAXIS: Occurrence of post-traumatic seizures
The occurrence of post-traumatic seizures. This will be assessed by follow-up questionnaire.
Time frame: Within 24 months post traumatic brain injury
MAST-PROPHYLAXIS: Time to post-traumatic seizure
The time to post traumatic seizure. This will be assessed by follow-up questionnaire.
Time frame: Within 24 months post traumatic brain injury
Both trials: Disability
Levels of disability will be assessed using the Extended Glasgow Outcome Scale via follow-up questionnaire. The scale is scored from 1 (death) to 8 (upper good recovery) with higher scores reflecting a better outcome.
Time frame: At 6, 12, 18 and 24 months
Both trials: Cognitive function
Cognitive function will be assessed using the Neurobehavioural Symptom Inventory via follow-up questionnaire. Symptoms are scored from 0 (mild) to 4 (very severe) with higher scores reflecting a worse outcome.
Time frame: At 6, 12, 18 and 24 months
Both trials: Quality of life
Quality of life will be assessed using the EQ-5D-5L via follow-up questionnaire. The EQ-5D-5L consists of 2 parts - the EQ-5D-5L descriptive system and the EQ Visual Analogue scale. The descriptive system comprises 5 dimensions (mobility, self care, usual activities, pain/discomfort, anxiety/depression) which are scored from 1 (no problems) to 5 (extreme problems) with higher scores reflecting a worse outcome. The EQ Visual Analogue scale is numbered 0 to 100 with higher scores reflecting a better outcome.
Time frame: At 6, 12, 18 and 24 months
Both trials: Adverse events
Adverse events will be assessed using the Liverpool Adverse Events Profile via follow-up questionnaire. The questionnaire is scored from 1 (never a problem) to 4 (always or often a problem) with higher scores reflecting a worse outcome.
Time frame: At 6, 12, 18 and 24 months
Both trials: Hospital admissions
Hospital admissions will be extracted from the NHS Digital Hospital Episode Statistics (HES) database) and equivalents. Hospital admissions will be combined with the length of anti-epileptic drug treatment to report an economic evaluation.
Time frame: Within 24 months post traumatic brain injury
Both trials: Frequency of PTS
The frequency of post traumatic seizures.
Time frame: Within 24 months post traumatic brain injury
Both trials: Mortality
Death from any cause
Time frame: At 6, 12, 18 and 24 months
Both trials: Frequency of adverse events of special interest
Frequency of adverse events of special interest (unfavourable and unintended sign, symptom, or disease temporally associated with the use of trial drug, whether or not considered related to the trial drug.
Time frame: Up to 24 months
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