- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04573803
Pharmacological Management of Seizures Post Traumatic Brain Injury (MAST)
Pharmacological Management of Seizures Post Traumatic Brain Injury (MAST)
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Anticipated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Samantha Lawes, PhD
- Phone Number: 07891 432226
- Email: samantha.lawes@addenbrookes.nhs.uk
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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.
|
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.
Other Names:
|
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.
|
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.
Other Names:
|
Experimental: MAST PROPHYLAXIS - Phenytoin Sodium
TBI patients, without an acute symptomatic seizure, will receive a 7-day course of Phenytoin Sodium as seizure prophylaxis.
|
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.
|
Dosing will be as prescribed clinically by the treating physician.Levetiracetam may be administered orally, intravenously or via nasogastric tube.
Other Names:
|
No Intervention: MAST PROPHYLAXIS - no treatment
TBI patients, without an acute symptomatic seizure, will not receive any anti-epileptic drug.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
MAST-DURATION: Occurrence of late PTS
Time Frame: 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.
|
Within 24 months post traumatic brain injury
|
MAST-PROPHYLAXIS: Occurrence of PTS
Time Frame: 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.
|
Within 2 weeks post TBI
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
MAST-PROPHYLAXIS: Occurrence of post-traumatic seizures
Time Frame: Within 24 months post traumatic brain injury
|
The occurrence of post-traumatic seizures.
This will be assessed by follow-up questionnaire.
|
Within 24 months post traumatic brain injury
|
MAST-PROPHYLAXIS: Time to post-traumatic seizure
Time Frame: Within 24 months post traumatic brain injury
|
The time to post traumatic seizure.
This will be assessed by follow-up questionnaire.
|
Within 24 months post traumatic brain injury
|
Both trials: Disability
Time Frame: 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.
|
At 6, 12, 18 and 24 months
|
Both trials: Cognitive function
Time Frame: 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.
|
At 6, 12, 18 and 24 months
|
Both trials: Quality of life
Time Frame: 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.
|
At 6, 12, 18 and 24 months
|
Both trials: Adverse events
Time Frame: 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.
|
At 6, 12, 18 and 24 months
|
Both trials: Hospital admissions
Time Frame: 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.
|
Within 24 months post traumatic brain injury
|
Both trials: Frequency of PTS
Time Frame: Within 24 months post traumatic brain injury
|
The frequency of post traumatic seizures.
|
Within 24 months post traumatic brain injury
|
Both trials: Mortality
Time Frame: At 6, 12, 18 and 24 months
|
Death from any cause
|
At 6, 12, 18 and 24 months
|
Both trials: Frequency of adverse events of special interest
Time Frame: 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.
|
Up to 24 months
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Peter Hutchinson, PhD, University of Cambridge
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neurologic Manifestations
- Craniocerebral Trauma
- Trauma, Nervous System
- Brain Injuries
- Wounds and Injuries
- Brain Injuries, Traumatic
- Seizures
- Molecular Mechanisms of Pharmacological Action
- Membrane Transport Modulators
- Anticonvulsants
- Voltage-Gated Sodium Channel Blockers
- Sodium Channel Blockers
- Cytochrome P-450 CYP1A2 Inducers
- Cytochrome P-450 Enzyme Inducers
- Nootropic Agents
- Levetiracetam
- Phenytoin
Other Study ID Numbers
- A095460
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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