E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Post traumatic seizures following traumatic brain injury |
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E.1.1.1 | Medical condition in easily understood language |
Seizures following brain injury |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10039911 |
E.1.2 | Term | Seizures (incl subtypes) |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
MAST_PROPHYLAXIS: To determine the comparative clinical effectiveness (absolute difference in the rate of PTS within the first 2 weeks post-TBI) of a 7-day course of phenytoin or levetiracetam, used as seizure prophylaxis, versus no AED for TBI patients
MAST-DURATION: To determine the comparative clinical effectiveness (absolute difference in the rate of late PTS within 24 months post-TBI) of a longer course of AED (at least 6 months) versus a shorter course (up to 3 months) for TBI patients with early seizures.
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E.2.2 | Secondary objectives of the trial |
MAST-PROPHYLAXIS: 1. Compare the rate of PTS within 24 months post-TBI 2. Compare outcomes (extended Glasgow Outcome Scale), cognitive function (Neurobehavioural Symptom Inventory), quality of life (EQ-5D-5L), and adverse events (Liverpool Adverse Events Profile) at 6, 12, 18 and 24 months, between the three arms. 3. Undertake a detailed economic evaluation. 4. To compare the frequency of PTS between the three arms. 5. Mortality at 6, 12, 18 and 24 months. 6. Adverse events of special interest during treatment.
MAST-DURATION: 1. Compare outcomes (extended Glasgow Outcome Scale), cognitive function (Neurobehavioural Symptom Inventory), quality of life (EQ-5D-5L), and adverse events (Liverpool Adverse Events Profile) at 6, 12, 18 and 24 months, between the two arms. 2. Undertake a detailed economic evaluation. 3. To compare the frequency of PTS between the two arms. 4. Mortality at 6, 12, 18 and 24 months. 5. Adverse events of special interest during treatment.
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E.2.3 | Trial contains a sub-study | No |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The MAST-PROPHYLAXIS sub-study Version 1.0 04.02.2020
This is an extended follow up period (additional 3 years)to provide additional information to inform DVLA guidelines. Currently, if an individual has a seizure of any kind,they need to stop driving and tell the DVLA. Licences can be withheld until the individual has been seizure free for up to 10 years, resulting in loss of employment for some people. Clearer evidence regarding seizure prophylaxis may help to inform these guidelines.
This sub-study will continue to follow up the participants in the prophylaxis trial for an additional three years to assess long term seizure occurrence and neuropsychiatric outcomes. This will be conducted by annual postal questionnaires. This sub-study is subject to additional funding being sourced.
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E.3 | Principal inclusion criteria |
MAST-PROPHYLAXIS: 1. Patients aged aged ≥10 years with acute TBI managed in NSU without an acute 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 randomisation within 48 hours of admittance.
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
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E.4 | Principal exclusion criteria |
MAST-PROPHYLAXIS: 1. Post-traumatic seizures 2. Un-survivable injury 3. Previous history of epilepsy 4. Patients who are taking an AED pre-TBI 5. Pregnancy or breastfeeding 6. Any known hypersensitivity to study drugs (or hydantoins or pyrrolidone derivatives) or any of their excipients 7. Time interval from the time of admission to NSU to randomisation exceeds 48 hours
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
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E.5 End points |
E.5.1 | Primary end point(s) |
MAST-PROPHYLAXIS: Occurrence of PTS within 2 weeks after TBI. MAST-DURATION: Occurrence of late PTS within 24 months after TBI.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
MAST-DURATION: Primary outcome - day 1, discharge, 6, 12, 18 and 24 months. MAST-PROPHYLAXIS: Primary outcome - day 7 and day 14
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E.5.2 | Secondary end point(s) |
Secondary outcomes (both trials: - questionnaires (functional outcomes, neurobehavioral symptoms, HRQOL) - Economic evaluation - Adverse events
Secondary outcomes (MAST-PROPHYLAXIS ONLY): - occurrence/frequency of PTS within 24 months |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Both trials: All questionnaires at 6, 12, 18 and 24 months. Economic evaluation at 24 months Adverse events during treatment only
Secondary outcomes (MAST-PROPHYLAXIS ONLY): - occurrence/frequency of PTS at 6, 12, 18 and 24 months |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
No treatment (PROPHYLAXIS TRIAL ONLY) |
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E.8.2.4 | Number of treatment arms in the trial | 5 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 29 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the main trial will be the date of the last patient’s final assessment/loss to follow-up |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 1 |