Pharmacological Management of Seizures Post Traumatic Brain Injury

NCT ID: NCT04573803

Last Updated: 2020-11-03

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 1649 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-01
• Study Completion Date: 2028-03-01

Brief 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. 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.

Conditions

Traumatic Brain Injury; Post Traumatic Seizures

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

MAST DURATION - <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.

Group Type: EXPERIMENTAL

Phenytoin Sodium

Intervention Type: DRUG

Dosing will be as prescribed clinically by the treating physician. Phenytoin Sodium may be administered orally, intravenously or via nasogastric tube.

Levetiracetam

Intervention Type: DRUG

Dosing will be as prescribed clinically by the treating physician.Levetiracetam may be administered orally, intravenously or via nasogastric tube.

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.

Group Type: EXPERIMENTAL

Phenytoin Sodium

Intervention Type: DRUG

Dosing will be as prescribed clinically by the treating physician. Phenytoin Sodium may be administered orally, intravenously or via nasogastric tube.

Levetiracetam

Intervention Type: DRUG

Dosing will be as prescribed clinically by the treating physician.Levetiracetam may be administered orally, intravenously or via nasogastric tube.

MAST PROPHYLAXIS - Phenytoin Sodium

TBI patients, without an acute symptomatic seizure, will receive a 7-day course of Phenytoin Sodium as seizure prophylaxis.

Group Type: EXPERIMENTAL

Phenytoin Sodium

Intervention Type: DRUG

Dosing will be as prescribed clinically by the treating physician. Phenytoin Sodium may be administered orally, intravenously or via nasogastric tube.

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.

Group Type: EXPERIMENTAL

Levetiracetam

Intervention Type: DRUG

Dosing will be as prescribed clinically by the treating physician.Levetiracetam may be administered orally, intravenously or via nasogastric tube.

MAST PROPHYLAXIS - no treatment

TBI patients, without an acute symptomatic seizure, will not receive any anti-epileptic drug.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Phenytoin Sodium

Dosing will be as prescribed clinically by the treating physician. Phenytoin Sodium may be administered orally, intravenously or via nasogastric tube.

Intervention Type: DRUG

Levetiracetam

Dosing will be as prescribed clinically by the treating physician.Levetiracetam may be administered orally, intravenously or via nasogastric tube.

Intervention Type: DRUG

Other Intervention Names

Keppra

Eligibility Criteria

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

• 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.

Exclusion Criteria

• 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

• Minimum Eligible Age: 10 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Cambridge

OTHER

Sponsor Role: collaborator

Cambridge University Hospitals NHS Foundation Trust

OTHER

Sponsor Role: lead

Responsible Party

Peter Hutchinson

Professor of Neurosurgery & Honorary Consultant Neurosurgeon

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Peter Hutchinson, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Cambridge

Central Contacts

Samantha Lawes, PhD

Role: CONTACT

samantha.lawes@addenbrookes.nhs.uk

07891 432226

Other Identifiers

A095460

Identifier Type: -

Identifier Source: org_study_id