Pilot trial comparing different fluid amounts given in the earliest stages of treatment in children presenting to UK emergency departments with a severe infection

ISRCTN	ISRCTN15244462
DOI	https://doi.org/10.1186/ISRCTN15244462
Protocol serial number	16SM3292
Sponsor	Imperial College Heathcare NHS Trust
Funder	National Institute for Health Research

Submission date: 03/08/2016
Registration date: 11/08/2016
Last edited: 18/09/2023

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
Septic shock is a life-threatening condition in which the blood pressure drops to dangerously low levels because of a serious blood infection (sepsis). Children are now much more likely to survive a septic shock than ever before. This progress comes from a whole package of treatments including antibiotics, multiple rapid doses (boluses) of fluid (saline (salt water) solution) into a child’s veins (‘fluid bolus therapy’) and support for breathing and heart function. This study is looking at refining the fluid bolus therapy part of this package by exploring what the best amount of fluid to give in the earliest stages of treatment is. In order to explore this, the study will monitor children to find out if giving less fluid per bolus to children with symptoms of a septic shock is better than giving a higher amount of fluid, as currently recommended. The aim of this study is to conduct a small version of the study to find out how feasible the study methods are and to find out if it is possible to recruit enough children to take part.

Who can participate?
Children under 16 years of age who are showing signs of septic shock, their parents or legal guardians, and hospital research teams.

What does the study involve?
In the first part of this study, children are randomly allocated to one of two groups. Those in the first group receive the current recommended bolus (dose) fluid therapy, of 20 ml/kg (maximum 1000 ml per bolus) every 15 minutes for four hours, until the signs of shock have gone or there are signs of fluid overload (a condition where there is too much fluid in the blood). Those in the second group receive smaller boluses of 10 ml/kg (maximum 500 ml per bolus) according to the same schedule. The type of fluids and other treatments given are left up to the medical team to decide. For both groups, the amount of fluid given to the children is recorded. In the second part of the study, parents/legal guardians of children participating in the first part of the study complete a number of questionnaires and telephone interviews to find out their views on the study process. Three focus groups with the hospital research teams are also held to explore their experiences of the study processes and consenting parents/legal representatives to the first part of the study.

What are the possible benefits and risks of participating?
It is not known whether there will be any additional benefits involved with participating in this study, however this study will help to improve the future treatment of children with septic shock. There are no notable risks involved with taking part.

Where is the study run from?
Thirteen NHS children’s hospitals in England (UK)

When is the study starting and how long is it expected to run for?
December 2015 to April 2017

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

Who is the main contact?
1. Dr David Inwald (scientific)
2. Ms Ruth Canter (public) (ruth.canter@icnarc.org)

Contact information

Dr David Inwald
Scientific

Paediatric Intensive Care Unit
Queen Elizabeth The Queen Mother (QEQM) Wing
St Mary's Hospital
Praed Street
London
W2 1NY
United Kingdom

Ms Ruth Canter
Public

ICNARC CTU
Napier House
24 High Holborn
London
WC1V 6AZ
United Kingdom

Phone	+44 (0)207 269 9277
Email	ruth.canter@icnarc.org

Study information

Primary study design	Interventional
Study design	Mixed methods: 1. Multicentre, pragmatic, open, pilot randomised controlled trial 2. Qualitative questionnaires, interviews and focus groups
Secondary study design	Randomised controlled trial
Participant information sheet	ISRCTN15244462_PIS.pdf
Scientific title	External pilot study of the Fluids in Shock (FiSh) trial
Study acronym	FiSh Pilot Study
Study objectives	The aim of this study is to explore and test important key parameters needed to inform the design and ensure the successful conduct of the FiSh trial.
Ethics approval(s)	London - Stanmore Research Ethics Committee, 14/06/2016, ref: 16/LO/0854
Health condition(s) or problem(s) studied	Sepsis/Septic shock
Intervention	Patients are randomised 1:1 using sealed opaque envelopes available at each site. Intervention: Restrictive bolus fluid resuscitation of 10 ml/kg (maximum 500 ml per bolus) Control: Current recommended bolus fluid resuscitation of 20 ml/kg (maximum 1000 ml per bolus) Fluids to be delivered every 15 minutes for four hours, until clinical signs of shock has resolved or there are signs of fluid overload. Type of fluid and all other treatments are at the discretion of the treating clinician.
Intervention type	Other
Primary outcome measure(s)	Feasibility of the intervention processes is determined by the evaluation of all the secondary outcomes at the end of the study, including a recommendation, or not, to continue to a larger trial.
Key secondary outcome measure(s)	1. Eligibility rate is measured using the proportion of eligible patients randomised, as recorded on the screening and enrolment log at baseline 2. Recruitment rate is measured using the number of patients randomised per site per month, as recorded on the enrolment log and study database at baseline 3. Proportion of parents/guardians refusing deferred consent is measured using data recorded on the enrolment log and study database at hospital discharge or end of study (dependent upon timing of approach) 4. Proportion of fluid boluses delivered at correct volume and time during the intervention period is measured using data recorded on patient medical notes and the study database between randomisation and four hours post-randomisation 5. Total volume of fluid received during the intervention period is measured using data recorded on patient medical notes and the study database between randomisation and four hours post-randomisation 6. Proportion of complete data for each outcome measure is measured using data recorded on patient medical notes, the study database and linkage with routine data sources between randomisation and 30 days post-randomisation 7. Time taken for data collection and entry is measured using data from feedback from site staff during focus groups at the end of the study 8. Proportion of required data able to be linked to routine sources is measured using routine sources specification at the end of the study 9. Adverse events are measured using data recorded on patient medical notes and the study database between randomisation and 30 days post-randomisation
Completion date	30/04/2017

Eligibility

Participant type(s)	Mixed
Age group	Child
Lower age limit	37 Weeks
Upper age limit	16 Years
Sex	All
Target sample size at registration	108
Total final enrolment	75
Key inclusion criteria	Pilot RCT: Children: 1. Age greater than or equal to 37 weeks (corrected gestational age) and less than 16 years 2. Clinical suspicion of infection 3. Clinical signs of shock after receipt of 20 ml/kg of bolus fluid 4. Recruitment and randomisation to take place while child is in an acute assessment area (e.g. emergency department, paediatric assessment unit (PAU)) Observational component: Parent/Guardian inclusion criteria (questionnaire component): Parent/Guardians who were approached for consent prior to hospital discharge Parent/Guardian inclusion criteria (telephone interview component): Parent/Guardians who were approached for consent Site research staff: Site research staff who are involved in screening, recruiting, randomising and consenting during the pilot RCT.
Key exclusion criteria	Pilot RCT: Children: 1. Prior receipt of more than 20 ml/kg of bolus fluid 2. Conditions in which bolus fluid resuscitation should be curtailed (e.g. raised intracranial pressure, diabetic ketoacidosis, known/suspected myocarditis/cardiomyopathy) 3. Full active resuscitation not within current goals of care Observational component: Parent/Guardian exclusion criteria (questionnaire and telephone interview): Parents/Guardians who do not speak English.
Date of first enrolment	13/07/2016
Date of final enrolment	31/03/2017

Locations

Countries of recruitment

United Kingdom
England

Study participating centres

St Mary's Hospital

Praed Street
London
W2 1NY
United Kingdom

Great Ormond Street Hospital for Children

Great Ormond Street
London
WC1N 3JH
United Kingdom

Bristol Royal Hospital for Children

Paul O'Gorman Building
Upper Maudlin Street
Bristol
BS2 8BJ
United Kingdom

Southampton General Hospital

Tremona Road
Southampton
SO16 6YD
United Kingdom

Chelsea and Westminster Hospital

369 Fulham Road
London
SW10 9NH
United Kingdom

Watford General Hospital

Vicarage Road
Watford
London
WD18 0HB
United Kingdom

Whittington Hospital

Magdala Avenue
London
N19 5NF
United Kingdom

Queen Alexandra Hospital

Southwick Hill Road
Portsmouth
PO6 3LY
United Kingdom

Musgrove Park Hospital

Parkfield Drive
Taunton
TA1 5DA
United Kingdom

Royal Devon and Exeter Hospital

Barrack Road
Exeter
EX2 5DW
United Kingdom

Royal United Hospital

Combe Park
Bath
BA1 3NG
United Kingdom

Northwick Park Hospital

Watford Road
Harrow
HA1 3UJ
United Kingdom

Salisbury District Hospital

Odstock Road
Salisbury
SP2 8BJ
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results in Health Technology Assessment journal	01/09/2018		Yes	No
Results article	results	01/05/2019	24/01/2020	Yes	No
Results article	Qualitative interview study results	28/08/2017	18/09/2023	Yes	No
HRA research summary			28/06/2023	No	No
Participant information sheet	For use in feasibility study interviews		18/09/2023	No	Yes
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Additional files

ISRCTN15244462_PIS.pdf: For use in feasibility study interviews

Editorial Notes

18/09/2023: Publication reference and patient information sheet added.
24/01/2020: Publication reference and total final enrolment number added.
24/09/2018: Publication reference added.
09/08/2018: Publication reference added.
03/03/2017: internal review.
23/12/2016: The following changes have been made to the record:
1. Basingstoke and North Hampshire Hospital and Royal Hampshire County Hospital have been removed from the list of participating centres and Salisbury District Hospital has been added
2. The recruitment start date has been updated from 13/06/2016 to 13/07/2016