Clinical trial NCT04573803: Pharmacological Management of Seizures Post Traumatic Brain Injury
Official title: Pharmacological Management of Seizures Post Traumatic Brain Injury (MAST)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Traumatic Brain Injury
Post Traumatic Seizures
Keywords: Phenytoin
Levetiracetam
Post-traumatic seizure
Traumatic brain injury
Lead sponsor: Cambridge University Hospitals NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: University of Cambridge
First posted: 2020-10-05
Enrollment: 1649
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: PREVENTION

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).

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.

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

Primary outcomes:
measure: MAST-DURATION: Occurrence of late PTS
timeFrame: Within 24 months post traumatic brain injury
measure: MAST-PROPHYLAXIS: Occurrence of PTS
timeFrame: Within 2 weeks post TBI
Secondary outcomes:
measure: MAST-PROPHYLAXIS: Occurrence of post-traumatic seizures
timeFrame: Within 24 months post traumatic brain injury
measure: MAST-PROPHYLAXIS: Time to post-traumatic seizure
timeFrame: Within 24 months post traumatic brain injury
measure: Both trials: Disability
timeFrame: At 6, 12, 18 and 24 months
measure: Both trials: Cognitive function
timeFrame: At 6, 12, 18 and 24 months
measure: Both trials: Quality of life
timeFrame: At 6, 12, 18 and 24 months
measure: Both trials: Adverse events
timeFrame: At 6, 12, 18 and 24 months
measure: Both trials: Hospital admissions
timeFrame: Within 24 months post traumatic brain injury
measure: Both trials: Frequency of PTS
timeFrame: Within 24 months post traumatic brain injury
measure: Both trials: Mortality
timeFrame: At 6, 12, 18 and 24 months
measure: Both trials: Frequency of adverse events of special interest
timeFrame: Up to 24 months
Other outcomes:
Locations:
Study officials:
affiliation: University of Cambridge
name: Peter Hutchinson, PhD
role: PRINCIPAL_INVESTIGATOR
References: