Cluster randomised trial of an intervention to promote implementation of clinical guidance on the management of suspected encephalitis

ISRCTN	ISRCTN06886935
DOI	https://doi.org/10.1186/ISRCTN06886935
Protocol serial number	14688
Sponsor	University of Liverpool (UK)
Funder	National Institute for Health Research

Submission date: 22/07/2013
Registration date: 22/07/2013
Last edited: 11/12/2018

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

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

Contact information

Dr Ruth Backman
Scientific

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

Email	R.Backman@liverpool.ac.uk

Study information

Primary study design	Interventional
Study design	Cluster randomised controlled interventional trial
Secondary study design	Cluster randomised trial
Study type	Participant information sheet
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
Study acronym	ENCEPH UK Intervention RCT
Study objectives	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(s)	NRES committee North West - Preston, 03/05/2013, ref:13/NW/0279
Health condition(s) or problem(s) studied	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
Primary outcome measure(s)	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.
Key secondary outcome measure(s)	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.
Completion date	15/07/2016

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	1680
Key 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
Key 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
Date of first enrolment	03/02/2014
Date of final enrolment	31/05/2015

Locations

Countries of recruitment

United Kingdom
England
Wales

Study participating centres

Blackpool Victoria Hospital

Blackpool
FY3 8NR
United Kingdom

Queen Elizabeth Hospital

Gateshead
NE9 6SX
United Kingdom

Queen Alexandra Hospital

Portsmouth
PO6 3LY
United Kingdom

Doncaster Royal Infirmary

Doncaster
DN2 5LT
United Kingdom

Stepping Hill Hospital

Stockport
SK2 7JE
United Kingdom

Whiston Hospital

Prescot
L35 5DR
United Kingdom

University Hospital Coventry and Warwick

Coventry
CV2 2DX
United Kingdom

Addenbrooke's Hospital

Cambridge
CB2 0QQ
United Kingdom

Countess of Chester Hospital

Chester
CH2 1UL
United Kingdom

North Devon District Hospital

Devon
EX31 4JB
United Kingdom

North Tees Hospital

Stockton-on-Tees
TS19 8PE
United Kingdom

Bedford Hospital

Bedford
MK42 9DJ
United Kingdom

Gloucestershire Royal Hospital

Gloucester
GL1 3NN
United Kingdom

King's Mill Hospital

Sutton-in-Ashfield
NG17 4JL
United Kingdom

Royal Sussex County Hospital

Brighton
BN2 5BE
United Kingdom

Ormskirk and Southport Hospital

Ormskirk
L39 2AZ
United Kingdom

West Suffolk Hospital

Bury St Edmunds
IP33 2QZ
United Kingdom

Leicester Royal Infirmary

Leicester
LE1 5WW
United Kingdom

Russells Hall Hospital

Dudley
DY1 2HQ
United Kingdom

Luton and Dunstable Hospital

Bedford
LU4 0DZ
United Kingdom

Great Western Hospital

Swindon
SN3 6BB
United Kingdom

Ysbyty Gwynedd

Gwynedd
LL57 2PW
United Kingdom

East Surrey Hospital

Redhill
RH1 5RH
United Kingdom

Chesterfield Royal Hospital

Chesterfield
S44 5BL
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Other
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/12/2015		Yes	No
Results article	results	06/12/2018		Yes	No
Protocol article	protocol	27/01/2015		Yes	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

11/12/2018: Publication reference added.
05/12/2017: internal review