Condition category
Nervous System Diseases
Date applied
19/10/2020
Date assigned
20/10/2020
Last edited
26/11/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

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

Trial website

https://masttrial.org/

Contact information

Type

Scientific

Primary contact

Prof Peter Hutchinson

ORCID ID

http://orcid.org/0000-0002-2796-1835

Contact details

Clinical Neurosciences
Box 167
Hills Road
Cambridge Biomedical Campus
Cambridge
CB2 0QQ
United Kingdom
+44 (0)1223 336946
pjah2@cam.ac.uk

Type

Public

Additional contact

Dr Samantha Lawes

ORCID ID

http://orcid.org/0000-0002-9666-3444

Contact details

Cambridge Clinical Trials Unit
Box 401 Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom
+44 (0)1223 256624
samantha.lawes@addenbrookes.nhs.uk

Additional identifiers

EudraCT number

2020-000282-16

ClinicalTrials.gov number

Nil known

Protocol/serial number

CCTU0235, IRAS 276415, HTA - NIHR128226, CTA 24551/0044/001-0001

Study information

Scientific title

Pharmacological management of seizures post traumatic brain injury (MAST trial)

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

Approval pending, 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), REC ref: 20/EE/0252

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

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

The PIS will be made available on the website https://masttrial.org/

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

Phase

Phase III

Drug names

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 trial start date

05/01/2020

Overall trial end date

01/03/2026

Reason abandoned (if study stopped)

Eligibility

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 type

Patient

Age group

Mixed

Gender

Both

Target number of participants

MAST-DURATION: 428 patients; MAST-PROPHYLAXIS: 1221 patients

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

01/03/2021

Recruitment end date

01/03/2024

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Addenbrookes Hospital
Cambridge University Hospitals NHS Foundation Trust Hills Road
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Freeman Hospital
Freeman Road High Heaton
Newcastle Upon Tyne
NE7 7DN
United Kingdom

Trial participating centre

Derriford Hospital
Derriford Road
Plymouth
PL6 8DH
United Kingdom

Trial participating centre

Royal Preston Hospital
Sharoe Green Lane Fulwood
Preston
PR2 9HT
United Kingdom

Trial participating centre

Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

Trial participating centre

Queen Elizabeth Hospital
Mindelsohn Way Edgbaston
Birmingham
B15 2GW
United Kingdom

Trial participating centre

Walsgrave General Hospital
Clifford Bridge Road
Coventry
CV2 2DX
United Kingdom

Trial participating centre

Queens Medical Centre
Derby Road
Nottingham
NG7 2UH
United Kingdom

Trial participating centre

St. Mary's Hospital
The Bays South Wharf Road
London
W2 1BL
United Kingdom

Trial participating centre

James Cook University Hospital
Marton Road
Middlesbrough
TS4 3BW
United Kingdom

Trial participating centre

Northern General Hospital
Herries Road
Sheffield
S5 7AU
United Kingdom

Trial participating centre

University Hospital Aintree
Lower Lane
Liverpool
L9 7AL
United Kingdom

Trial participating centre

St. James's University Hospital
Beckett Street
Leeds
LS9 7TF
United Kingdom

Trial participating centre

Royal Sussex County Hospital
Eastern Road
Brighton
BN2 5BE
United Kingdom

Trial participating centre

NHS Grampian
Summerfield House 2 Eday Road
Aberdeen
AB15 6RE
United Kingdom

Trial participating centre

NHS Lothian
Waverley Gate 2-4 Waterloo Place
Edinburgh
EH1 3EG
United Kingdom

Trial participating centre

NHS Greater Glasgow and Clyde
1055 Great Western Road
Glasgow
G12 0XH
United Kingdom

Trial participating centre

Southmead Hospital
Southmead Road Westbury-On-Trym
Bristol
BS10 5NB
United Kingdom

Trial participating centre

Cardiff & Vale University LHB
Heath Park
Cardiff
CF14 4XW
United Kingdom

Trial participating centre

St George's Hospital
Blackshaw Road Tooting
London
SW17 0QT
United Kingdom

Trial participating centre

The Royal London Hospital
Whitechapel
London
E1 1BB
United Kingdom

Trial participating centre

Hull Royal Infirmary
Anlaby Road
Hull
HU3 2JZ
United Kingdom

Trial participating centre

NHS Tayside
Kings Croos Clepington Road
Dundee
DD3 8EA
United Kingdom

Trial participating centre

Salford Royal
Stott Lane
Salford
M6 8HD
United Kingdom

Trial participating centre

University Hospitals of North Midlands NHS Trust
Newcastle Road
Stoke-On-Trent
ST4 6QG
United Kingdom

Trial participating centre

King's College Hospital
Denmark Hill
London
SE5 9RS
United Kingdom

Trial participating centre

John Radcliffe Hospital
Headley Way Headington
Oxford
OX3 9DU
United Kingdom

Trial participating centre

Queens Hospital
Rom Valley Way
Romford
RM7 0AG
United Kingdom

Trial participating centre

Belfast City Hospital
Lisburn Road
Belfast
BT9 7AB
United Kingdom

Sponsor information

Organisation

Cambridge University Hospitals NHS Foundation Trust

Sponsor details

Hills Road
Cambridge
CB2 0QQ
United Kingdom
+44 (0)1223 254472
cctu@addenbrookes.nhs.uk

Sponsor type

Hospital/treatment centre

Website

http://www.cuh.org.uk/

Organisation

University of Cambridge

Sponsor details

Trinity Lane
Cambridge
CB2 1TN
United Kingdom
+44 (0)1223 337733
researchgovernance@medschl.cam.ac.uk

Sponsor type

University/education

Website

http://www.cam.ac.uk/

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

Results and Publications

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 statement
The data-sharing plans for the current study are unknown and will be made available at a later date

Intention to publish date

01/03/2029

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

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.