Condition category
Nervous System Diseases
Date applied
13/08/2014
Date assigned
27/08/2014
Last edited
09/04/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Most epileptic seizures and convulsions in children last less than three minutes and will stop on their own accord. However, on occasion, a seizure may continue for longer than three minutes and eventually become what is called convulsive status epilepticus (CSE). This is a medical emergency. To prevent CSE from happening, children are given an antiepileptic medicine called an emergency or rescue medicine (also known as first-line treatment). owever, this treatment will only be successful in around half of all children. In those cases where the rescue medicine is not successful, the children need to be taken to the Accident and Emergency Department (AED) of their local hospital. Once there, if the child is still in the seizure, they are given a different rescue medicine. This again will be successful in stopping the seizure in about half of the children. For those that are still in seizure, a different medicine is then given (this medicine is known as second-line treatment). The usual medicine given at this stage is called phenytoin. However, again it only has an approximately 50% success rate and has to be given very carefully because it can cause very unpleasant and very serious side-effects, including those that may affect the heart, blood pressure and skin. Some early results of a new anticonvulsant called levetiracetam suggest that this medicine may work better and be safer than phenytoin. In this study, we want to see if this is really the case.

Who can participate?
Children between 6 months and 18 years of age in CSE which has not stopped after being given first-line treatment.

What does the study involve?
The children are randomly allocated into one of two groups. Those in group 1 are given intravenous levetiracetam. Those in group 2 are given intravenous phenytoin. The children's progress is then followed for 24 hours. We want to see how long it takes for the seizure to stop after the drugs have been given, whether any further medicine has to be given, whether the child needs to go the intensive care unit, and whether the child develops any unwanted side-effects.

What are the possible benefits and risks of participating?
Phenytoin will only stop CSE is approximately 50-60% of cases and has to be given slowly to avoid a drop in blood pressure and irregular heart beat (cardiac arrhythmias). It may also cause irritation of the veins and inflammation. Levetiracetam may stop CSE in more than 70% of cases. Risks of taking levetiracetam may include dizziness, feeling sleepy and headache.

Where is the study run from?
Institute of Child Health, Alder Hey Children's NHS Foundation Trust (UK)

When is the study starting and how long is it expected to run for?
March 2015 to April 2018

Who is funding the study?
National Institute for Health Research HTA (UK)

Who is the main contact?
Ms Amy Humphreys
eclipse.trial@liverpool.ac.uk

Trial website

http://www.eclipse-study.org.uk/

Contact information

Type

Scientific

Primary contact

Ms Amy Humphreys

ORCID ID

Contact details

Medicines for Children Clinical Trials Unit
Clinical Trials Research Centre
University of Liverpool
Institute of Child Health
Alder Hey Children's NHS Foundation Trust
Liverpool
L12 2AP
United Kingdom
-
eclipse.trial@liverpool.ac.uk

Additional identifiers

EudraCT number

2014-002188-13

ClinicalTrials.gov number

Protocol/serial number

HTA 12/127/134

Study information

Scientific title

Emergency Treatment with Levetiracetam or Phenytoin in Status Epilepticus in Children (EcLiPSE) – an open-label randomised controlled trial

Acronym

EcLiPSE

Study hypothesis

1. To determine whether intravenous levetiracetam or intravenous phenytoin is the more effective second-line anticonvulsant for the emergency management of convulsive status epilepticus (CSE) in children
2. To determine if intravenous levetiracetam is associated with fewer adverse side-effects than intravenous phenytoin

More details can be found at http://www.nets.nihr.ac.uk/projects/hta/12127134
Protocol can be found at http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0014/123350/PRO-12-127-134.pdf

On 09/04/2015 the following changes were made to the trial record:
1. The scientific title was changed from 'Emergency Treatment with Levetiracetam or Phenytoin in Status Epilepticus in Children (EcLiPSE) - a randomised unblinded controlled trial' to 'Emergency Treatment with Levetiracetam or Phenytoin in Status Epilepticus in Children (EcLiPSE) – an open-label randomised controlled trial'.
2. The target number of participants was changed from 340 to 308.

Ethics approval

NRES committee North West – Liverpool central, 03/03/2015, REC ref: 15/NW/0090

Study design

Multicentre unblinded active comparator randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Status epilepticus

Intervention

Eligible children will be randomised to receive either intravenous Levetiracetam 40 mg/kg administered as an infusion over 5 minutes or intravenous Phenytoin 20 mg/kg administered as an infusion over 20 minutes. Trial intervention is administered as a single infusion of the allocated treatment. Total duration of follow-up is 24 hours.

Added 09/04/2015: Maximum dose of levetiracetam is 2500 mg and maximum dose of phenytoin is 1000 mg.

Intervention type

Drug

Phase

Phase IV

Drug names

Levetiracetam, Phenytoin

Primary outcome measures

Time to cessation of all visible signs of convulsive seizure activity

Secondary outcome measures

1. Need for further anticonvulsant(s) to manage the seizure after the initial agent
2. Need for rapid sequence induction (RSI) with thiopentone or another agent (e.g. propofol) due to ongoing CSE
3. Need to be admitted to critical care
4. Serious adverse reactions including death, airway complications, and cardiovascular instability (cardiac arrest, arrhythmia and hypotension requiring intervention), extravasation injury ('purple-glove syndrome'), extreme agitation

Overall trial start date

01/03/2015

Overall trial end date

31/05/2018

Reason abandoned

Eligibility

Participant inclusion criteria

1. Males and females aged 6 months to 18 years (<18th birthday)
2. Presenting seizure is tonic-clonic, clonic or focal convulsive status epilepticus that requires second-line treatment to terminate the seizure

Added 09/04/2015:
3. Two doses of benzodiazepines administered in order to try and terminate the seizure
Note 1: Patients receiving oral phenytoin or levetiracetam as part of their regular oral anti-epileptic drug regime are eligible for this trial.
Note 2: If more than two doses of benzodiazepines are administered prior to admission to ED then these patients are still eligible for EcLiPSE.
Note 3: A very small number of families will have rectal paraldehyde rather than a rectal or buccal benzodiazepine as their child’s first-line rescue medication. These patients are eligible for EcLiPSE.

Participant type

Patient

Age group

Child

Gender

Both

Target number of participants

308

Participant exclusion criteria

1. Absence, myoclonic or non-convulsive status epilepticus, or infantile spasms
2. Known or suspected pregnancy
3. Known contra-indication or allergy to levetiracetam or phenytoin. This includes where the child's individual rescue (emergency) care plan states that the child never responds to, or has previously experienced a severe adverse reaction to, phenytoin, levetiracetam, or both
4. Known renal failure (patients on peritoneal or haemodialysis or with renal function <50% expected for age)
5. Previous administration of rectal paraldehyde or another second-line antiepileptic drug prior to arrival in the emergency department

Added 09/04/2015:
6. Known to have previously been randomised into EcLiPSE

Recruitment start date

01/03/2015

Recruitment end date

01/03/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Alder Hey Children's NHS Foundation Trust
Eaton Road
Liverpool
L12 2AP
United Kingdom

Trial participating centre

Arrowe Park Hospital
Arrowe Park Road
Wirral
CH49 5PE
United Kingdom

Trial participating centre

Birmingham Children's Hospital
Steelhouse Lane
Birmingham
B4 6NH
United Kingdom

Trial participating centre

Royal Alexandra Hospital Brighton
Eastern Road
Brighton
BN2 5BE
United Kingdom

Trial participating centre

Bristol Royal Hospital for Children
Paul O'Gorman Building Upper Maudlin Street
Bristol
BS2 8BJ
United Kingdom

Trial participating centre

Chelsea and Westminster Healthcare NHS Foundation Trust
369 Fulham Road
London
SW10 9NH
United Kingdom

Trial participating centre

Derbyshire Children's Hospital (at Royal Derby Hospital)
Uttoexter Road
Derby
DE22 3NE
United Kingdom

Trial participating centre

Royal Hospital for Sick Children Edinburgh
9 Sciennes Road
Edinburgh
EH9 1LF
United Kingdom

Trial participating centre

Evelina London Children's Hospital
Lambeth Palace Road
London
SE1 7EH
United Kingdom

Trial participating centre

Royal Devon & Exeter Hospital
Barrack Road
Exeter
EX2 5DW
United Kingdom

Trial participating centre

Royal Hospital for Sick Children Glasgow
Dalnair Street Yorkhill
Glasgow
G3 8SJ
United Kingdom

Trial participating centre

Crosshouse Hospital
Kilmarnock Road Crosshouse
Kilmarnock
KA2 0BE
United Kingdom

Trial participating centre

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

Trial participating centre

Leicester Royal Infirmary
Infirmary Square
Leicester
LE1 5WW
United Kingdom

Trial participating centre

Royal Manchester Children's Hospital
Oxford Road
Manchester
M13 9WL
United Kingdom

Trial participating centre

Queens Medical Centre
Derby Road
Nottingham
NG7 2UH
United Kingdom

Trial participating centre

Sheffield Children's Hospital
Western Bank
Sheffield
S10 2TH
United Kingdom

Trial participating centre

University Hospital Southampton
Tremona Road
Southampton
SO16 6YD
United Kingdom

Trial participating centre

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

Trial participating centre

Sunderland Royal Hospital
Kayll Road
Sunderland
SR4 7TP
United Kingdom

Sponsor information

Organisation

University of Liverpool (UK)

Sponsor details

c/o Ms Karen Wilding
Medicines for Children Clinical Trials Unit
University of Liverpool
Institute of Child Health
Alder Hey Children's NHS Foundation Trust
Liverpool
L12 2AP
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

NIHR HTA (HTA 12/127/134) (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

01/03/2019

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes