MAST: Pharmacological Management of Seizures Post Traumatic Brain Injury

Sponsor

Cambridge University Hospitals NHS Foundation Trust (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04573803

Collaborator

University of Cambridge (Other)

1,649

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Traumatic Brain Injury Post Traumatic Seizures	Drug: Phenytoin Sodium Drug: Levetiracetam	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1649 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

The MAST trial consists of two pragmatic, open-label, multi-centre, independent, parallel, randomised trials. MAST-DURATION consists of two arms and MAST-PROPHYLAXIS consists of three arms.The MAST trial consists of two pragmatic, open-label, multi-centre, independent, parallel, randomised trials. MAST-DURATION consists of two arms and MAST-PROPHYLAXIS consists of three arms.

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Pharmacological Management of Seizures Post Traumatic Brain Injury (MAST)

Anticipated Study Start Date :

Mar 1, 2021

Anticipated Primary Completion Date :

Mar 1, 2026

Anticipated Study Completion Date :

Mar 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MAST DURATION - <3 months TBI patients with early seizures (within first 7 days following trauma) will receive a short course of up to 3 months of either Phenytoin Sodium or Levetiracetam.	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. Other Names: Keppra
Experimental: MAST DURATION - >6 months TBI patients with early seizures (within first 7 days following trauma) will receive a longer course of at least 6 months of either Phenytoin Sodium or Levetiracetam.	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. Other Names: Keppra
Experimental: MAST PROPHYLAXIS - Phenytoin Sodium TBI patients, without an acute symptomatic seizure, will receive a 7-day course of Phenytoin Sodium as seizure prophylaxis.	Drug: Phenytoin Sodium Dosing will be as prescribed clinically by the treating physician. Phenytoin Sodium may be administered orally, intravenously or via nasogastric tube.
Experimental: MAST PROPHYLAXIS - Levetiracetam TBI patients, without an acute symptomatic seizure, will receive a 7-day course of Levetiracetam as seizure prophylaxis. Dosing will be as prescribed clinically by the treating physician.	Drug: Levetiracetam Dosing will be as prescribed clinically by the treating physician.Levetiracetam may be administered orally, intravenously or via nasogastric tube. Other Names: Keppra
No Intervention: MAST PROPHYLAXIS - no treatment TBI patients, without an acute symptomatic seizure, will not receive any anti-epileptic drug.

Outcome Measures

Primary Outcome Measures

MAST-DURATION: Occurrence of late PTS [Within 24 months post traumatic brain injury]
The primary outcome for MAST-DURATION is the occurrence of late post-traumatic seizure. This will be assessed by follow-up questionnaire.
MAST-PROPHYLAXIS: Occurrence of PTS [Within 2 weeks post TBI]
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.

Secondary Outcome Measures

MAST-PROPHYLAXIS: Occurrence of post-traumatic seizures [Within 24 months post traumatic brain injury]
The occurrence of post-traumatic seizures. This will be assessed by follow-up questionnaire.
MAST-PROPHYLAXIS: Time to post-traumatic seizure [Within 24 months post traumatic brain injury]
The time to post traumatic seizure. This will be assessed by follow-up questionnaire.
Both trials: Disability [At 6, 12, 18 and 24 months]
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.
Both trials: Cognitive function [At 6, 12, 18 and 24 months]
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.
Both trials: Quality of life [At 6, 12, 18 and 24 months]
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.
Both trials: Adverse events [At 6, 12, 18 and 24 months]
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.
Both trials: Hospital admissions [Within 24 months post traumatic brain injury]
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.
Both trials: Frequency of PTS [Within 24 months post traumatic brain injury]
The frequency of post traumatic seizures.
Both trials: Mortality [At 6, 12, 18 and 24 months]
Death from any cause
Both trials: Frequency of adverse events of special interest [Up to 24 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

10 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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