Comparing anti-epileptic treatments for seizures following traumatic brain injury
| ISRCTN | ISRCTN13200656 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13200656 |
| EudraCT/CTIS number | 2020-000282-16 |
| IRAS number | 276415 |
| ClinicalTrials.gov number | NCT04573803 |
| Secondary identifying numbers | CCTU0235, IRAS 276415, HTA - NIHR128226, CTA 24551/0044/001-0001 |
- Submission date
- 19/10/2020
- Registration date
- 20/10/2020
- Last edited
- 09/03/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Nervous System Diseases
Plain English Summary
Background and study aims
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 anti-epileptic 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 study aims to answer if one approach is better than the other (MAST-DURATION). The second part of the study 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).
Who can participate?
MAST-DURATION:
Patients aged 10 and over, with a traumatic brain injury, managed in a neurosurgical unit, who have started on phenytoin or levetiracetam due to an acute symptomatic seizure during acute hospitalisation.
MAST-PROPHYLAXIS:
Patients aged 10 and over, with a traumatic brain injury, managed in a neurosurgical unit, without an acute symptomatic seizure.
What does the study involve?
MAST-DURATION:
Patients will be randomly allocated to receive to a maximum of 3 months or a minimum of 6 months course of phenytoin or levetiracetam.
MAST-PROPHYLAXIS:
Patients will be randomly allocated to receive either phenytoin, levetiracetam or no anti-epileptic drug for a period of 7 days.
Current international guidelines for traumatic brain injury recommend the use of phenytoin for the prevention of early post-traumatic seizures, when the benefits are thought to outweigh the risks. In practice, alternative anti-epileptic drugs such as levetiracetam are being used clinically as they are associated with fewer risks.
Patients will be assessed for seizures during hospital admission and will also be asked to complete follow-up questionnaires at 6,12, 18 and 24 months.
What are the possible benefits and risks of participating?
MAST-DURATION:
The study drugs patients will be provided with are standard anti-epileptic drugs, used to control seizures. The researchers expect seizures to be reduced as a result of taking the study drug.
MAST-PROPHYLAXIS:
There is no guarantee that patients will benefit from taking part in this trial.
Apart from the potential side effects from the study drugs, there are no additional risks or disadvantages involved with taking part in this study. Patients will continue to receive the standard care for their condition.
Where is the study run from?
Addenbrookes Hospital (UK)
When is the study starting and how long is it expected to run for?
January 2020 to March 2026
Who is funding the study?
National Institute for Health Research (NIHR) (UK)
Who is the main contact?
1. Prof. Peter Hutchinson
pjah2@cam.ac.uk
2. Dr Samantha Lawes
samantha.lawes@addenbrookes.nhs.uk
Contact information
Scientific
Clinical Neurosciences, Box 167, Hills Road
Cambridge Biomedical Campus
Cambridge
CB2 0QQ
United Kingdom
 ORCID ID |
0000-0002-2796-1835 |
|---|---|
| Phone | +44 (0)1223 336946 |
| pjah2@cam.ac.uk |
Public
Cambridge Clinical Trials Unit
Box 401 Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom
| ORCID ID |
0000-0002-9666-3444 |
|---|---|
| Phone | +44 (0)1223 256624 |
| samantha.lawes@addenbrookes.nhs.uk |
Study information
| Study design | MAST-DURATION: Phase III randomized multicentre pragmatic parallel-group trial MAST-PROPHYLAXIS: Phase III randomized multicentre pragmatic parallel-group trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised parallel trial |
| Study setting(s) | Hospital |
| Study type | Prevention |
| Participant information sheet | The PIS will be made available on the website https://masttrial.org/ |
| Scientific title | Pharmacological management of seizures post traumatic brain injury (MAST trial) |
| Study acronym | MAST |
| Study hypothesis | MAST-DURATION: There will be a significant difference in the rate of late post-traumatic seizures (PTS) within 24 months post-traumatic brain injury between a longer course of phenytoin or levetiracetam (at least 6 months) and a shorter course (up to 3 months) in traumatic brain injury patients with early seizures. MAST-PROPHYLAXIS: There will be a significant difference in the rate of post-traumatic seizures within the first 2 weeks post-traumatic brain injury between a 7-day course of phenytoin, levetiracetam or no anti-epileptic drug. |
| Ethics approval(s) | Approved 11/01/2021, Cambridge East (East of England - Cambridge East Research Ethics Committee, The Fulbourn Centre, Home End, Fulbourn, Cambridgeshire, CB21 5BS, UK; +44 (0)207 104 8102; cambridgeeast.rec@hra.nhs.uk), ref: 20/EE/0252 |
| Condition | Post-traumatic seizures in traumatic brain injury patients |
| Intervention | MAST-DURATION: Patients will be randomized 1:1 to a maximum of 3 months OR a minimum of 6 months duration of a clinically prescribed AED (phenytoin or levetiracetam). MAST-PROPHYLAXIS: Patients will be randomized 1:1:1 to phenytoin, levetiracetam or no AED for a period of 7 days. Dosing for both parts of the trial will be as clinically prescribed and administered as per routine practice. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Phenytoin, levetiracetam |
| Primary outcome measure | MAST-DURATION: Occurrence of late PTS measured using self-report questionnaire within 24 months after TBI MAST-PROPHYLAXIS: Occurrence of PTS measured using clinical observation/self-report questionnaire within 2 weeks after TBI |
| Secondary outcome measures | 1. Occurrence of PTS measured using self-report questionnaire up to 2 years (MAST-PROPHYLAXIS only) 2. Levels of disability measured using Extended Glasgow Outcome Scale at 6, 12, 18 and 24 months 3. Cognitive function measured using Neurobehavioural Symptom Inventory at 6, 12, 18 and 24 months 4. Quality of life measured using EQ-5D-5L at 6, 12, 18 and 24 months 5. Adverse events measured using Liverpool Adverse Events Profile at 6, 12, 18 and 24 months 6. Economic evaluation using the EQ-5D-5L questionnaire at 6, 12, 18 and 24 months 7. Frequency of PTS measured using self-report questionnaire within 24 months post traumatic brain injury 8. Mortality measured using data from the Spine for patients in England, nurse telephone calls outside England at 6, 12, 18 and 24 months 9. Adverse events of special interest measured using reports from sites and self-report during treatment |
| Overall study start date | 05/01/2020 |
| Overall study end date | 01/03/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 10 Years |
| Sex | Both |
| Target number of participants | MAST-DURATION: 428 patients; MAST-PROPHYLAXIS: 1221 patients |
| Participant inclusion criteria | MAST-DURATION: 1. Patients aged ≥10 years with TBI managed in an NSU who have started on phenytoin or levetiracetam due to an acute symptomatic seizure during acute hospitalisation 2. 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 MAST-PROPHYLAXIS: 1. Patients aged ≥10 years, with TBI managed in an NSU without an acute symptomatic seizure 2. 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 |
| Participant exclusion criteria | MAST-DURATION: 1. Un-survivable injury 2. Previous history of epilepsy 3. Patients who are on an AED pre-TBI 4. Patient who has been clinically prescribed an AED to treat PTS (other than phenytoin or levetiracetam) since current admission 5. Any hypersensitivity to study drug selected or any of its excipients MAST-PROPHYLAXIS: 1. Post-traumatic seizures 2. Unsurvivable injury 3. Previous history of epilepsy 4. Patients who are on an AED pre-TBI 5. Pregnancy or breastfeeding 6. Any hypersensitivity to study drug (or hydantoins or pyrrolidone derivatives) or any of its excipients 7. Time interval from the time of admission to NSU to randomisation exceeds 48 hours |
| Recruitment start date | 05/03/2021 |
| Recruitment end date | 01/03/2024 |
Locations
Countries of recruitment
- England
- Northern Ireland
- Scotland
- United Kingdom
- Wales
Study participating centres
Hills Road
Cambridge
CB2 0QQ
United Kingdom
High Heaton
Newcastle Upon Tyne
NE7 7DN
United Kingdom
Plymouth
PL6 8DH
United Kingdom
Fulwood
Preston
PR2 9HT
United Kingdom
Southampton
SO16 6YD
United Kingdom
Edgbaston
Birmingham
B15 2GW
United Kingdom
Coventry
CV2 2DX
United Kingdom
Nottingham
NG7 2UH
United Kingdom
South Wharf Road
London
W2 1BL
United Kingdom
Middlesbrough
TS4 3BW
United Kingdom
Sheffield
S5 7AU
United Kingdom
Liverpool
L9 7AL
United Kingdom
Leeds
LS9 7TF
United Kingdom
Brighton
BN2 5BE
United Kingdom
2 Eday Road
Aberdeen
AB15 6RE
United Kingdom
2-4 Waterloo Place
Edinburgh
EH1 3EG
United Kingdom
Glasgow
G12 0XH
United Kingdom
Westbury-On-Trym
Bristol
BS10 5NB
United Kingdom
Cardiff
CF14 4XW
United Kingdom
Tooting
London
SW17 0QT
United Kingdom
London
E1 1BB
United Kingdom
Hull
HU3 2JZ
United Kingdom
Clepington Road
Dundee
DD3 8EA
United Kingdom
Salford
M6 8HD
United Kingdom
Stoke-On-Trent
ST4 6QG
United Kingdom
London
SE5 9RS
United Kingdom
Headington
Oxford
OX3 9DU
United Kingdom
Romford
RM7 0AG
United Kingdom
Belfast
BT9 7AB
United Kingdom
Sponsor information
Hospital/treatment centre
Hills Road
Cambridge
CB2 0QQ
England
United Kingdom
| Phone | +44 (0)1223 254472 |
|---|---|
| cctu@addenbrookes.nhs.uk | |
| Website | http://www.cuh.org.uk/ |
University/education
Trinity Lane
Cambridge
CB2 1TN
England
United Kingdom
| Phone | +44 (0)1223 337733 |
|---|---|
| researchgovernance@medschl.cam.ac.uk | |
| Website | http://www.cam.ac.uk/ |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/03/2029 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | The protocol will be made available on the website https://masttrial.org/ The findings of the MAST trial will be disseminated via peer-reviewed journals and presentations at national and international meetings. In addition to meetings orientated around neurosurgery, conferences organised for the different health professionals who care for patients post traumatic brain injury will be targeted. Research findings will be disseminated to relevant service user groups and charities through newsletters, website posts and public presentations. The MAST trial website will also include dedicated pages for members of the public. The trial will be presented in open days organised by hospitals participating in the trial where members of the public are invited to find out about ongoing research. Talks/presentations will also be given at meetings of local/regional relevant service user groups and charities. |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 26/07/2023 | No | No |
Editorial Notes
09/03/2021: The following changes were made to the trial record:
1. The recruitment start date was changed from 01/03/2021 to 05/03/2021.
2. The ClinicalTrials.gov number was added.
02/03/2021: The ethics approval was added.
26/11/2020: The CTA reference number was added to the protocol/serial no. field.
20/10/2020: Trial's existence confirmed by the NIHR.
