Pharmacological Management of Seizures Post Traumatic Brain Injury

NCT04573803 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: A095460
• Study Type: interventional
• Target: 1,649
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Traumatic Brain Injury; Post Traumatic Seizures

Keywords

Phenytoin; Levetiracetam; Post-traumatic seizure; Traumatic brain injury

Outcome Measures

Primary Outcomes (2)

• MAST-DURATION: Occurrence of late PTS

  The primary outcome for MAST-DURATION is the occurrence of late post-traumatic seizure. This will be assessed by follow-up questionnaire.

  Within 24 months post traumatic brain injury

• MAST-PROPHYLAXIS: Occurrence of PTS

  The primary outcome for MAST-PROPHYLAXIS is the occurrence of an acute symptomatic seizure. This will be assessed in the neurosurgical unit, or by telephone following discharge.

  Within 2 weeks post TBI

Secondary Outcomes (10)

• MAST-PROPHYLAXIS: Occurrence of post-traumatic seizures

  Within 24 months post traumatic brain injury

• MAST-PROPHYLAXIS: Time to post-traumatic seizure

  Within 24 months post traumatic brain injury

• Both trials: Disability

  At 6, 12, 18 and 24 months

• Both trials: Cognitive function

  At 6, 12, 18 and 24 months

• Both trials: Quality of life

  At 6, 12, 18 and 24 months

Study Arms (5)

MAST DURATION - <3 months

EXPERIMENTAL

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; Drug: Levetiracetam

MAST DURATION - >6 months

EXPERIMENTAL

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; Drug: Levetiracetam

MAST PROPHYLAXIS - Phenytoin Sodium

EXPERIMENTAL

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

Drug: Phenytoin Sodium

MAST PROPHYLAXIS - Levetiracetam

EXPERIMENTAL

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

MAST PROPHYLAXIS - no treatment

NO INTERVENTION

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

Interventions

Phenytoin Sodium DRUG

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

MAST DURATION - <3 months; MAST DURATION - >6 months; MAST PROPHYLAXIS - Phenytoin Sodium

Levetiracetam DRUG

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

Also known as: Keppra

MAST DURATION - <3 months; MAST DURATION - >6 months; MAST PROPHYLAXIS - Levetiracetam

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.
• 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)

Sponsors & Collaborators

• Cambridge University Hospitals NHS Foundation Trust: lead
• University of Cambridge: collaborator

MeSH Terms

Conditions

Brain Injuries, Traumatic

Interventions

Phenytoin; Levetiracetam

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Hydantoins; Imidazolidines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Pyrrolidinones; Pyrrolidines

Study Officials

• Peter Hutchinson, PhD

  University of Cambridge

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Samantha Lawes, PhD

CONTACT

07891 432226; samantha.lawes@addenbrookes.nhs.uk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurosurgery & Honorary Consultant Neurosurgeon

Model Details: The MAST trial consists of two pragmatic, open-label, multi-centre, independent, parallel, randomised trials. MAST-DURATION consists of two arms and MAST-PROPHYLAXIS consists of three arms.

Study Record Dates

• First Submitted: September 7, 2020
• First Posted: October 5, 2020
• Study Start: March 1, 2021
• Primary Completion: March 1, 2026
• Study Completion (Estimated): March 1, 2028
• Last Updated: November 3, 2020

Record last verified: 2020-09