Traumatic Brain InjuryPhase 3MASTNCT04573803
Pharmacological Management of Seizures Post Traumatic Brain Injury
A Phase 3 study testing Phenytoin Sodium and Levetiracetam in people with Traumatic Brain Injury and Post Traumatic Seizures, run by Cambridge University Hospitals NHS Foundation Trust.
Trial 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. Read more about this study
- Who is it for?
- Ages 10 years and older
- Conditions the study is for
- Traumatic Brain Injury, Post Traumatic Seizures
- What is being tested?
- Phenytoin Sodium and Levetiracetam
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,649 participants
- Where
- No sites listed yet
- Study dates
- 1 Mar 2021to 1 Mar 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
- 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.
Who cannot join
- 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
Show all 15Show fewer
- MAST-PROPHYLAXIS
- 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
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Pharmacological Management of Seizures Post Traumatic Brain Injury (MAST)
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).
Read the 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.
- Conditions
- Traumatic Brain Injury, Post Traumatic Seizures
- Being tested
- Phenytoin Sodium, Levetiracetam
- Keywords
- Phenytoin, Levetiracetam, Post-traumatic seizure, Traumatic brain injury
- Medical subject headings
- Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Phenytoin SodiumDrug
Dosing will be as prescribed clinically by the treating physician. Phenytoin Sodium may be administered orally, intravenously or via nasogastric tube.
LevetiracetamDrug
Also called Keppra
Dosing will be as prescribed clinically by the treating physician.Levetiracetam may be administered orally, intravenously or via nasogastric tube.
| Study group | Role | What they receive |
|---|---|---|
| MAST DURATION - <3 months | Experimental | 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. Receives: Drug: Phenytoin Sodium; Drug: Levetiracetam |
| MAST DURATION - >6 months | Experimental | 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. Receives: Drug: Phenytoin Sodium; Drug: Levetiracetam |
| MAST PROPHYLAXIS - Phenytoin Sodium | Experimental | TBI patients, without an acute symptomatic seizure, will receive a 7-day course of Phenytoin Sodium as seizure prophylaxis. Receives: Drug: Phenytoin Sodium |
| MAST PROPHYLAXIS - Levetiracetam | Experimental | 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. Receives: Drug: Levetiracetam |
| MAST PROPHYLAXIS - no treatment | No intervention | TBI patients, without an acute symptomatic seizure, will not receive any anti-epileptic drug. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Within 2 weeks post TBI
Secondary outcomes (10)
MAST-PROPHYLAXIS: Occurrence of post-traumatic seizures
The occurrence of post-traumatic seizures. This will be assessed by follow-up questionnaire.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Within 24 months post traumatic brain injury
Both trials: Frequency of PTS
The frequency of post traumatic seizures.
Measured: Within 24 months post traumatic brain injury
Both trials: Mortality
Death from any cause
Measured: 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.
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2020
- Study start1 Mar 2021 (estimated)
- Primary completion1 Mar 2026 (estimated)
- Study completion1 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 1,649 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cambridge University Hospitals NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University of Cambridge
- Responsible party
- Principal investigator, Peter Hutchinson, University of Cambridge
- Investigators
- Peter Hutchinson, PhD, Principal investigator, University of Cambridge
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04573803
- Sponsor's protocol ID
- A095460
- Acronym
- MAST
- Status last verified
- Sep 2020
- First submitted
- 7 Sep 2020
- Last updated
- 3 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacological Management of Seizures Post Traumatic Brain Injury (MAST)
- ClinicalTrials.gov ID
- NCT04573803
- Acronym / sponsor ID
- MAST / A095460
- Conditions
- Traumatic Brain Injury, Post Traumatic Seizures
- Keywords
- Phenytoin, Levetiracetam, Post-traumatic seizure, Traumatic brain injury
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 1,649 participants (estimated)
- Lead sponsor
- Cambridge University Hospitals NHS Foundation TrustUniversity, hospital or other
- Collaborators
- University of Cambridge
- Study start
- 1 Mar 2021 (estimated)
- Primary completion
- 1 Mar 2026 (estimated)
- Study completion
- 1 Mar 2028 (estimated)
- First posted
- 5 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
- 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.
| Arm | Type | Receives |
|---|---|---|
| MAST DURATION - <3 months | Experimental | Drug: Phenytoin Sodium, Drug: LevetiracetamTBI 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. |
| MAST DURATION - >6 months | Experimental | Drug: Phenytoin Sodium, Drug: LevetiracetamTBI 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. |
| MAST PROPHYLAXIS - Phenytoin Sodium | Experimental | Drug: Phenytoin SodiumTBI patients, without an acute symptomatic seizure, will receive a 7-day course of Phenytoin Sodium as seizure prophylaxis. |
| MAST PROPHYLAXIS - Levetiracetam | Experimental | Drug: LevetiracetamTBI 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. |
| MAST PROPHYLAXIS - no treatment | No intervention | –TBI patients, without an acute symptomatic seizure, will not receive any anti-epileptic drug. |
Who may qualify
- Ages
- 10 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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
- 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.
Key exclusion criteria (15 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Phenytoin SodiumDosing will be as prescribed clinically by the treating physician. Phenytoin Sodium may be administered orally, intravenously or via nasogastric tube. | Drug | MAST DURATION - <3 months, MAST DURATION - >6 months, MAST PROPHYLAXIS - Phenytoin Sodium |
| LevetiracetamAlso: KeppraDosing will be as prescribed clinically by the treating physician.Levetiracetam may be administered orally, intravenously or via nasogastric tube. | Drug | MAST DURATION - <3 months, MAST DURATION - >6 months, MAST PROPHYLAXIS - Levetiracetam |
Primary outcome
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.
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.
10 secondary outcomes
MAST-PROPHYLAXIS: Occurrence of post-traumatic seizures
Time frame: Within 24 months post traumatic brain injury
MAST-PROPHYLAXIS: Time to post-traumatic seizure
Time frame: Within 24 months post traumatic brain injury
Both trials: Disability
Time frame: At 6, 12, 18 and 24 months
Both trials: Cognitive function
Time frame: At 6, 12, 18 and 24 months
Both trials: Quality of life
Time frame: At 6, 12, 18 and 24 months
Both trials: Adverse events
Time frame: At 6, 12, 18 and 24 months
Both trials: Hospital admissions
Time frame: Within 24 months post traumatic brain injury
Both trials: Frequency of PTS
Time frame: Within 24 months post traumatic brain injury
Both trials: Mortality
Time frame: At 6, 12, 18 and 24 months
Both trials: Frequency of adverse events of special interest
Time frame: Up to 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2020.
Related trials for Traumatic Brain Injury
Active, not recruitingObservational study
Transforming Research and Clinical Knowledge in Traumatic Brain Injury Epileptogenesis Project (TRACK-TBI EPI)
Traumatic Brain Injury, Post-traumatic Epilepsy
Enrolling by invitationPhase 1
Pilot Safety and Exploratory Efficacy of PSC-05 for the Treatment of Chronic Mild Traumatic Brain Injury
Mild Traumatic Brain Injury
RecruitingObservational study
Intracranial Pressure Monitoring in Moderate Traumatic Brain Injury
Moderate Traumatic Brain Injury
Not yet recruitingPhase 1
Nanopulse Laser Therapy
TBI (Traumatic Brain Injury)
RecruitingObservational study
Effect of Different Intravenous Fluids on Post-operative Chronic Subdural Hematoma Size and Recurrence
Chronic Subdural Hematoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Peter Hutchinson, PhD principal investigator
University of Cambridge
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Phenytoin Sodium and Levetiracetam in people with Traumatic Brain Injury and Post Traumatic Seizures, run by Cambridge University Hospitals NHS Foundation Trust.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 3 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Samantha Lawes, PhD (07891 432226, samantha.lawes@addenbrookes.nhs.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MAST-DURATION: Occurrence of late PTS (time frame: Within 24 months post traumatic brain injury). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2020.