Condition category
Infections and Infestations
Date applied
22/07/2013
Date assigned
22/07/2013
Last edited
24/03/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Up to twenty eight hospitals will be recruited across the UK to take part in this study which will evaluate the effects of an intervention to improve the clinical management of patients with suspected encephalitis (inflammation of the brain) in secondary care. This will involve assessing adherence to the national guidelines for encephalitis and developing and applying an intervention to improve adherence. The development of the intervention will be informed by existing evidence on professional behaviour change and sub-studies within the ENCEPH UK programme. The intervention will target clinicians responsible for the diagnosis and initial management of suspected encephalitis. Cost effectiveness and clinical outcomes will be assessed. The study aims to give clinicians evidence-based tools to help them implement the national guidance for management of suspected encephalitis patients.

Who can participate?
Any patients in whom encephalitis should have been suspected within the recruited sites will be included in the study.

What does the study involve?
Hospitals will be randomly allocated to either the standard care group or the intervention group. The intervention will target clinicians responsible for the diagnosis and initial management of suspected encephalitis. Nurses will collect data from the patients' notes and this will be recorded on the data collection forms in a similar style to a clinical audit. No identifiable data such as name or NHS number will be recorded; the patients' date of birth and gender will be collected so that we can categorise the population. The hospital will keep the key of which patient has been allocated to each number so that data queries can be checked; however, this encryption key will remain at the hospital.

What are the possible benefits and risks of participating?
Ideally, all hospitals should be following accepted best practice in the care of suspected encephalitis. However, we know this is not the case. Should the intervention be effective, patient care in intervention hospitals should improve. We do not foresee any additional risks to patients in either group of the study.

Where is the study run from?
This study is being run by Brain Infections UK within The University of Liverpool. Up to 28 hospitals will be recruited across the UK.

When is the study starting and how long is it expected to run for?
This study is due to start data collection in January 2014 and will run for a further 2 years.

Who is funding the study?
National Institute of Health Research (UK).

Who is the main contact?
Prof Tom Solomon, Chief Investigator
Dr Ruth Backman, Trial Coordinator, R.Backman@liverpool.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Ruth Backman

ORCID ID

Contact details

Trial Coordinator ENCEPH UK Intervention RCT
Institute of Infection and Global Health
Ronald Ross Building
University of Liverpool
8 West Derby Street
Liverpool
L69 7BE
United Kingdom
-
R.Backman@liverpool.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

14688

Study information

Scientific title

Development and evaluation of an intervention based around the national guidelines on the management of suspected encephalitis, and its evaluation through a cost-effectiveness analysis

Acronym

ENCEPH UK Intervention RCT

Study hypothesis

Up to 28 hospitals will be recruited across the UK to take part in this cluster randomised controlled trial which will evaluate the effects of an intervention to improve the clinical management of suspected encephalitis in secondary care. The cost effectiveness of the intervention will also be assessed. The study will be run over two years including a 12-month follow-up intervention period.

Within this study we will compare the rate of diagnosis for encephalitis between the 'routine' hospitals and ‘intervention’ hospitals. The development of the intervention will be informed by existing evidence on professional behaviour change and sub-studies within the ENCEPH UK programme. The intervention will target clinicians responsible for the diagnosis and initial management of suspected encephalitis. The use of a cluster randomised controlled trial in up to twenty eight hospitals with a follow-up period of 12 months will allow both cost effectiveness and clinical outcomes to be assessed.

The main outcome will be the proportion of patients with suspected encephalitis appropriately investigated and started on treatment with aciclovir within 6 hours and those patients that had a lumbar puncture performed within 12 hours (unless it was clinically contraindicated).

Added 07/01/2015:
We will explore the outcome data to examine any relationship between the method of inclusion and compliance of the primary outcomes and if there is a difference in case mix, our modelled primary outcome analysis will adjust for this.

More details can be found at: http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=14688

Ethics approval

NRES committee North West - Preston, 03/05/2013, ref:13/NW/0279

Study design

Cluster randomised controlled interventional trial

Primary study design

Interventional

Secondary study design

Cluster randomised trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

For this study we will not be actively recruiting patients as it is a retrospective notes review which is in a similar style to a robust clinical audit. Therefore there are no patient information sheets associated with this project.

Condition

Topic: Infection; Subtopic: Infection (all Subtopics); Disease: Infectious diseases and microbiology

Intervention

Package 1, there will be a series of interventions within the package that will be clinical led to help implement the national guidelines for management of suspected encephalitis patients.

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

Current primary outcome measures as of 07/01/2015:
The proportion of patients with suspected encephalitis whose care met all of the following criteria:
1. Aciclovir given within 6 hours of admission to hospital
2. A LP was performed within 12 hours of hospital arrival unless clinically contraindicated

Previous primary outcome measures:
The proportion of patients with suspected encephalitis whose care met all of the following criteria:
1. Aciclovir given within 6 hours of admission to hospital at the appropriate dose unless there was an alternative diagnosis
2. A LP was performed within 12 hours of hospital arrival unless clinically contraindicated.

Secondary outcome measures

Current secondary outcome measures as of 07/01/2015:
1. The proportion of all adults started on intravenous (IV) aciclovir within an appropriate dosage range for a neurological presentation who met the definition of suspected encephalitis
2. The proportion of all children started on intravenous (IV) aciclovir within an appropriate dosage range for a neurological presentation who met the definition of suspected encephalitis
3. The proportion of patients with suspected encephalitis who had a lumbar puncture performed within 12 hours unless there was a clinical contraindication
4. The proportion of patients with suspected encephalitis who had a lumbar puncture at any time within the index presentation
5. The proportion of patients with suspected encephalitis who had either MRI or CT scan within 24 hours of admission
6. The proportion of patients with suspected encephalitis having had a lumbar puncture, who had the following CSF investigations performed:
6.1. CSF:serum glucose ratio calculated
6.2. HSV PCR performed
7. An evaluation of the primary outcomes comparing adults and children enrolled in the RCT
8. A cost-effectiveness evaluation of the intervention

Previous secondary outcome measures:
1. The proportion of all adults given intravenous (IV) aciclovir for a neurological presentation who met the definition of suspected encephalitis.
2. The proportion of all children given IV aciclovir for a neurological presentation who met the definition of suspected encephalitis.
3. The proportion of patients with suspected encephalitis who had a lumbar puncture performed within 12 hours unless there was a clinical contraindication.
4. The proportion of patients with suspected encephalitis who had a lumbar puncture after resolution of a clinical contraindication to that LP.
5. The proportion of patients with suspected encephalitis who had either MRI or CT scan within 24 hours of admission.
6. For patients with HSV encephalitis, the proportion who die, have sequelae and appear to make a full recovery upon discharge.
7. The proportion of patients with suspected encephalitis having had a lumbar puncture, who had the following CSF investigations performed:
7.1. CSF:serum glucose ratio calculated
7.2. HSV PCR performed
8. An evaluation of the primary outcomes comparing adults and children enrolled in the RCT.
9. A cost-effectiveness evaluation of the intervention.

Overall trial start date

20/01/2014

Overall trial end date

15/07/2016

Reason abandoned

Eligibility

Participant inclusion criteria

Site inclusion criteria:
All centres will have a consultant and all centres must be equipped with the ability to perform, or have access to CT/MRI scans and have aseptic conditions for conducting a LP to be performed. Hospitals will be randomised as a unit to either the standard care or intervention arm. Study centres will be initiated once all global (e.g. local research and development [R&D] approval) and study-specific conditions (e.g. training requirements) have been met, and all necessary documents have been returned to the Brain Infections UK coordinating centre.
Within this study, any patients who have suspected encephalitis within the recruited sites will be included in the study. The inclusion criteria for suspected encephalitis are:

Patients with suspected encephalitis
(a) Mandatory
Acute or sub-acute (<4 weeks) alteration in consciousness, cognition, personality or behaviour persisting for more than 24 hours. Personality/behaviour change includes: agitation, psychosis, somnolence, insomnia, catatonia, mood liability, altered sleep pattern and (in children): new onset enuresis, or irritability.
Plus ANY two of:
1. Fever (> 38ºC) / prodromal illness – acute or sub-acute
2. Seizures: new onset
3. Focal neurological signs – acute or sub-acute onset. These include:
3.1. Focal weakness
3.2. Oromotor dysfunction
3.3. Movement disorders (chorea, athetosis, dystonia, hemiballisms, stereotypies, orolingual dyskinesia and tics) including Parkinsonism (bradykinesia, tremor, rigidity and postural instability)
3.4. Amnesia
4. Pleocytosis: cerebrospinal fluid white cell count >4 cells/ul
5. Neuroimaging: compatible with encephalitis
6. Electroencephalogram (EEG): compatible with encephalitis
OR
(b) Clinical suspicion of encephalitis but above investigations have not yet been completed
OR
(c) Clinical suspicion of encephalitis and the patient died before investigations completed

Target Gender: Male & Female

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: Up to 1680; UK Sample Size: 1120 Up to 1680

Participant exclusion criteria

Site exclusion criteria:
Current participation in the ENCEPH UK programme

Added 07/01/2015:
Patient exclusion criteria
Any patient aged under 28 days upon the date of admission shall be excluded

Recruitment start date

03/02/2014

Recruitment end date

31/05/2015

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Blackpool Victoria Hospital
Blackpool
FY3 8NR
United Kingdom

Trial participating centre

Queen Elizabeth Hospital
Gateshead
NE9 6SX
United Kingdom

Trial participating centre

Queen Alexandra Hospital
Portsmouth
PO6 3LY
United Kingdom

Trial participating centre

Doncaster Royal Infirmary
Doncaster
DN2 5LT
United Kingdom

Trial participating centre

Stepping Hill Hospital
Stockport
SK2 7JE
United Kingdom

Trial participating centre

Whiston Hospital
Prescot
L35 5DR
United Kingdom

Trial participating centre

University Hospital Coventry and Warwick
Coventry
CV2 2DX
United Kingdom

Trial participating centre

Addenbrooke's Hospital
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Countess of Chester Hospital
Chester
CH2 1UL
United Kingdom

Trial participating centre

North Devon District Hospital
Devon
EX31 4JB
United Kingdom

Trial participating centre

North Tees Hospital
Stockton-on-Tees
TS19 8PE
United Kingdom

Trial participating centre

Bedford Hospital
Bedford
MK42 9DJ
United Kingdom

Trial participating centre

Gloucestershire Royal Hospital
Gloucester
GL1 3NN
United Kingdom

Trial participating centre

King's Mill Hospital
Sutton-in-Ashfield
NG17 4JL
United Kingdom

Trial participating centre

Royal Sussex County Hospital
Brighton
BN2 5BE
United Kingdom

Trial participating centre

Ormskirk and Southport Hospital
Ormskirk
L39 2AZ
United Kingdom

Trial participating centre

West Suffolk Hospital
Bury St Edmunds
IP33 2QZ
United Kingdom

Trial participating centre

Leicester Royal Infirmary
Leicester
LE1 5WW
United Kingdom

Trial participating centre

Russells Hall Hospital
Dudley
DY1 2HQ
United Kingdom

Trial participating centre

Luton and Dunstable Hospital
Bedford
LU4 0DZ
United Kingdom

Trial participating centre

Great Western Hospital
Swindon
SN3 6BB
United Kingdom

Trial participating centre

Ysbyty Gwynedd
Gwynedd
LL57 2PW
United Kingdom

Trial participating centre

East Surrey Hospital
Redhill
RH1 5RH
United Kingdom

Trial participating centre

Chesterfield Royal Hospital
Chesterfield
S44 5BL
United Kingdom

Sponsor information

Organisation

University of Liverpool (UK)

Sponsor details

University of Liverpool / Liverpool Joint Research Office
2nd Floor Block D Waterhouse Building
3 Brownlow Street
Liverpool
L69 3GL
United Kingdom
-
sponsor@liv.ac.uk

Sponsor type

University/education

Website

http://www.liv.ac.uk/

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

The protocol is published and can be found at http://www.implementationscience.com/content/10/1/14. The paper describing the formation of the intervention package has been editorially accepted and we will publish the final trial results and a process evaluation at the end of data collection.

Intention to publish date

Participant level data

Other

Results - basic reporting

Publication summary

2015 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/25623603
2015 results in: http://www.implementationscience.com/content/10/1/37

Publication citations

Additional files

Editorial Notes