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Pharmacological Management of Seizures Post Traumatic Brain Injury (MAST)

Primary Purpose

Traumatic Brain Injury, Post Traumatic Seizures

Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Phenytoin Sodium
Levetiracetam
Sponsored by
Cambridge University Hospitals NHS Foundation Trust
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Traumatic Brain Injury focused on measuring Phenytoin, Levetiracetam, Post-traumatic seizure, Traumatic brain injury

Eligibility Criteria

10 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    No Intervention

    Arm Label

    MAST DURATION - <3 months

    MAST DURATION - >6 months

    MAST PROPHYLAXIS - Phenytoin Sodium

    MAST PROPHYLAXIS - Levetiracetam

    MAST PROPHYLAXIS - no treatment

    Arm Description

    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.

    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.

    TBI patients, without an acute symptomatic seizure, will receive a 7-day course of Phenytoin Sodium as seizure prophylaxis.

    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.

    TBI patients, without an acute symptomatic seizure, will not receive any anti-epileptic drug.

    Outcomes

    Primary Outcome Measures

    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.
    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.

    Secondary Outcome Measures

    MAST-PROPHYLAXIS: Occurrence of post-traumatic seizures
    The occurrence of post-traumatic seizures. This will be assessed by follow-up questionnaire.
    MAST-PROPHYLAXIS: Time to post-traumatic seizure
    The time to post traumatic seizure. This will be assessed by follow-up questionnaire.
    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.
    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.
    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.
    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.
    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.
    Both trials: Frequency of PTS
    The frequency of post traumatic seizures.
    Both trials: Mortality
    Death from any cause
    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.

    Full Information

    First Posted
    September 7, 2020
    Last Updated
    November 2, 2020
    Sponsor
    Cambridge University Hospitals NHS Foundation Trust
    Collaborators
    University of Cambridge
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04573803
    Brief Title
    Pharmacological Management of Seizures Post Traumatic Brain Injury
    Acronym
    MAST
    Official Title
    Pharmacological Management of Seizures Post Traumatic Brain Injury (MAST)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2020
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    March 1, 2021 (Anticipated)
    Primary Completion Date
    March 1, 2026 (Anticipated)
    Study Completion Date
    March 1, 2028 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Cambridge University Hospitals NHS Foundation Trust
    Collaborators
    University of Cambridge

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. 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).
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Traumatic Brain Injury, Post Traumatic Seizures
    Keywords
    Phenytoin, Levetiracetam, Post-traumatic seizure, Traumatic brain injury

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    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.
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    1649 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    MAST DURATION - <3 months
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    MAST DURATION - >6 months
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    MAST PROPHYLAXIS - Phenytoin Sodium
    Arm Type
    Experimental
    Arm Description
    TBI patients, without an acute symptomatic seizure, will receive a 7-day course of Phenytoin Sodium as seizure prophylaxis.
    Arm Title
    MAST PROPHYLAXIS - Levetiracetam
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    MAST PROPHYLAXIS - no treatment
    Arm Type
    No Intervention
    Arm Description
    TBI patients, without an acute symptomatic seizure, will not receive any anti-epileptic drug.
    Intervention Type
    Drug
    Intervention Name(s)
    Phenytoin Sodium
    Intervention Description
    Dosing will be as prescribed clinically by the treating physician. Phenytoin Sodium may be administered orally, intravenously or via nasogastric tube.
    Intervention Type
    Drug
    Intervention Name(s)
    Levetiracetam
    Other Intervention Name(s)
    Keppra
    Intervention Description
    Dosing will be as prescribed clinically by the treating physician.Levetiracetam may be administered orally, intravenously or via nasogastric tube.
    Primary Outcome Measure Information:
    Title
    MAST-DURATION: Occurrence of late PTS
    Description
    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
    Title
    MAST-PROPHYLAXIS: Occurrence of PTS
    Description
    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
    Secondary Outcome Measure Information:
    Title
    MAST-PROPHYLAXIS: Occurrence of post-traumatic seizures
    Description
    The occurrence of post-traumatic seizures. This will be assessed by follow-up questionnaire.
    Time Frame
    Within 24 months post traumatic brain injury
    Title
    MAST-PROPHYLAXIS: Time to post-traumatic seizure
    Description
    The time to post traumatic seizure. This will be assessed by follow-up questionnaire.
    Time Frame
    Within 24 months post traumatic brain injury
    Title
    Both trials: Disability
    Description
    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
    Title
    Both trials: Cognitive function
    Description
    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
    Title
    Both trials: Quality of life
    Description
    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
    Title
    Both trials: Adverse events
    Description
    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
    Title
    Both trials: Hospital admissions
    Description
    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
    Title
    Both trials: Frequency of PTS
    Description
    The frequency of post traumatic seizures.
    Time Frame
    Within 24 months post traumatic brain injury
    Title
    Both trials: Mortality
    Description
    Death from any cause
    Time Frame
    At 6, 12, 18 and 24 months
    Title
    Both trials: Frequency of adverse events of special interest
    Description
    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

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    10 Years
    Accepts Healthy Volunteers
    No
    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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Samantha Lawes, PhD
    Phone
    07891 432226
    Email
    samantha.lawes@addenbrookes.nhs.uk
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Peter Hutchinson, PhD
    Organizational Affiliation
    University of Cambridge
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

    Pharmacological Management of Seizures Post Traumatic Brain Injury

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