| CTRI Number |
CTRI/2024/05/067626 [Registered on: 20/05/2024] Trial Registered Prospectively |
| Last Modified On: |
18/05/2024 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
Which medicine is better for fits after head injury and when should one start it. |
|
Scientific Title of Study
|
Management of Seizures after Traumatic brain injury |
| Trial Acronym |
MAST |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dhaval Shukla |
| Designation |
Professor, Neurosurgery |
| Affiliation |
National Institute of Mental Health and Neurosciences, Bengaluru |
| Address |
Neurosurgery Unit 3,
Room no. NS110, Gate 3, OPD Block, MH Marigowda Road, National Institute of Mental Health and Neurosciences (NIMHANS)
Hosur Road, Near Bangalore Milk Dairy
Bangalore
KARNATAKA
5600029
India |
| Phone |
9898073843 |
| Fax |
|
| Email |
neurodhaval@rediffmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dhaval Shukla |
| Designation |
Professor, Neurosurgery |
| Affiliation |
National Institute of Mental Health and Neurosciences, Bengaluru |
| Address |
Neurosurgery Unit 3,
Room no. NS110, Gate 3, OPD Block, MH Marigowda Road, National Institute of Mental Health and Neurosciences (NIMHANS)
Hosur Road, Near Bangalore Milk Dairy
KARNATAKA
5600029
India |
| Phone |
9898073843 |
| Fax |
|
| Email |
neurodhaval@rediffmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dhaval Shukla |
| Designation |
Professor, Neurosurgery |
| Affiliation |
National Institute of Mental Health and Neurosciences, Bengaluru |
| Address |
Neurosurgery Unit 3,
Room no. NS110, Gate 3, OPD Block, MH Marigowda Road, National Institute of Mental Health and Neurosciences (NIMHANS)
Hosur Road, Near Bangalore Milk Dairy
KARNATAKA
5600029
India |
| Phone |
9898073843 |
| Fax |
|
| Email |
neurodhaval@rediffmail.com |
|
|
Source of Monetary or Material Support
|
| National Institute of Mental Health and Neurosciences,(NIMHANS)
Hosur Road, Near Bangalore Milk Dairy,
Bengluru, Karnataka - 5600029 |
|
|
Primary Sponsor
|
| Name |
National Institute of Mental Health and Neurosciences (NIMHANS) |
| Address |
Hosur Road, Near Bangalore Milk Dairy,
Bengluru, Karnataka 5600029 |
| Type of Sponsor |
Research institution and hospital |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| National Institute for Health and Care Research |
Nuffield Department of Primary Care Health Sciences, Radcliffe Observatory Quarter, Woodstock Road, Oxford OX2 6GG. |
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| DrDhaval Shukla |
NIMHANS |
Emergency care block,
trauma centre, ground
floor,NIMHANS
Bangalore
KARNATAKA
Bangalore
KARNATAKA |
9898073843
neurodhaval@rediffmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| NIMHANS Ethics committe (Basic and Neurosciences division) |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: G405||Epileptic seizures related to external causes, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
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. |
Drug: Phenytoin Sodium
Dosing will be as prescribed clinically by the treating physician. Phenytoin Sodium may be administered orally, intravenously or via nasogastric tube.
dose is 5-8 mg /kg per day in two or three divided doses. Usually 500 mg three times a day
Drug: Levetiracetam
Dosing will be as prescribed clinically by the treating physician.Levetiracetam may be administered orally, intravenously or via nasogastric tube.
Usual dose is 500 mg twice a day
Other Names:
Keppra |
| Intervention |
MAST DURATION less than 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.
Drug: Phenytoin Sodium
Dosing will be as prescribed clinically by the treating physician. Phenytoin Sodium may be administered orally, intravenously or via nasogastric tube. The usual dose is 5-8 mg / kg divided two times daily
Drug: Levetiracetam
Dosing will be as prescribed clinically by the treating physician.Levetiracetam may be administered orally, intravenously or via nasogastric tube.
The usual dose is 500 mg twice a day. (maximum dose can be 3000 mg per day)
|
| Comparator Agent |
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. |
Drug: Levetiracetam
Dosing will be as prescribed clinically by the treating physician.Levetiracetam may be administered orally, intravenously or via nasogastric tube.
The usual dose is 500 mg twice a day |
| Intervention |
MAST PROPHYLAXIS - Phenytoin Sodium
TBI patients, without an acute symptomatic seizure, will receive a 7-day course of Phenytoin Sodium as seizure prophylaxis. |
Drug: Phenytoin Sodium
Dosing will be as prescribed clinically by the treating physician. Phenytoin Sodium may be administered orally, intravenously or via nasogastric tube.
The usual dose is 5-8 mg /kg per day and this comes to 500 mg thrice a day |
|
|
Inclusion Criteria
|
| Age From |
10.00 Year(s) |
| Age To |
90.00 Year(s) |
| Gender |
Male |
| Details |
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
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. |
|
| ExclusionCriteria |
| Details |
MAST DURATION
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
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
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
MAST-DURATION: the occurrence of late post-traumatic seizure.
MAST-PROPHYLAXIS: is the occurrence of an acute symptomatic seizure. |
MAST-DURATION: Within 24 months post traumatic brain injury
MAST-PROPHYLAXIS: Occurrence of post-traumatic seizures within 2 weeks post TBI
|
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| • Extended Glasgow Outcome Scale, Neurobehavioural Symptom Inventory, quality of life (EQ-5D-5L), and Liverpool Adverse Events |
At 6, 12, 18 and 24 months |
| THe frequency of post traumatic seizures |
Within 24 months post traumatic brain injury |
| Mortality |
Death from any cause |
| 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 |
|
|
Target Sample Size
|
Total Sample Size="1649"
Sample Size from India="1649"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
01/06/2024 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="3"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
Brief Study Protocol Post-traumatic seizures (PTS) are a common complication of traumatic brain injury (TBI), affecting up to ~15 % of closed TBIs. PTS may impair brain metabolism with potentially severe consequences on patients’ neurological outcomes and a significant impact on healthcare costs. The evidence supporting the use of antiepileptic drugs (AEDs) for the management of PTS remains very low, with consequent ambiguity in the latest guidelines for TBI management. In this context, MAST Prophylaxis was developed to address the issue of preventing PTS. The MAST trial is already registered with EudraCT Number: 2020-000282-16 and ISRCTN Number: ISRCTN13200656 The study is funded by the NIHR HTA Programme and it is sponsored by the University of Cambridge. Due to longstanding collaboration and shared research interest with the Neurosurgical Department at NIMHANS, the latter Institute will launch an equivalent study in India. The study will mirror the ongoing UK trial. Purpose of clinical trial | To assess 1. Anti-epileptic drug (AED) prophylaxis following traumatic brain injury (TBI) (MAST-PROPHYLAXIS) 2. Duration of AED treatment following post- traumatic seizure(s) (PTS) (MAST- DURATION) This will be assessed by conducting 2 parallel but independent trials. Eligibility to enter either trial will be dependent on whether an early seizure has occurred. | Trial Design | MAST-PROPHYLAXIS: Phase 3, randomised multi-centre, pragmatic, parallel group trial. MAST-DURATION: Phase 3, randomised multicentre, pragmatic, parallel group trial Both studies will start with an internal pilot study. | Trial Outcome Measures | Primary outcome measure: · MAST-PROPHYLAXIS: Occurrence of PTS within 2 weeks after TBI. · MAST-DURATION: Occurrence of late PTS within 24 months after TBI. Secondary outcome measures: · PTS up to 2 years (MAST-PROPHYLAXIS only) · Extended Glasgow Outcome Scale, Neurobehavioural Symptom Inventory, quality of life (EQ-5D-5L), and Liverpool Adverse Events Profile at 6, 12, 18 and 24 months. · Economic evaluation · Frequency of PTS · Mortality at 6, 12, 18 and 24 months. · Adverse events of special interest during treatment. | Sample Size | Recruitment of: MAST-PROPHYLAXIS: 1221 participants in total (130 in an internal pilot) MAST-DURATION: 428 participants in total (50 in an internal pilot) |
|