Plain English Summary
Background and study aims
Around 20,000 children are admitted to paediatric intensive care units (PICU) each year in the UK. Around 75% of children admitted to PICU will receive additional oxygen, often in combination with a ventilator. Doctors and nurses adjust oxygen treatment based on how much oxygen their patient has in their blood, known as oxygen saturations. Whilst it is known that very low oxygen saturations are harmful, current research shows that very high saturations may also be dangerous for very ill people. Recent research in adults has shown that high oxygen saturations can lead to worse outcomes in emergencies like heart attacks and strokes. It is not known whether this harm is an effect of the oxygen level itself or a side-effect of the treatments given to keep oxygen levels high. Because of the differences in child and adult bodies, the results of this research cannot be applied to children. The aim of this study is to find out whether children in intensive care who are receiving oxygen while needing help from a ventilator should have their oxygen saturations kept at a lower level (88-92%, which is within recommended guidelines) or at the level currently used (95-100%).
Who can participate?
Children aged under 16 from 15 NHS PICUs who are receiving oxygen while needing help from a ventilator
What does the study involve?
Participants are randomly allocated to the higher or lower oxygen saturation group which ensures that the two groups are as similar as possible. All other medical care is decided by the doctors and nurses. All participants are followed up after 90 days and one year to see how they are after leaving PICU.
What are the possible benefits and risks of participating?
The researchers cannot promise any benefit directly by participating in this study. The benefits and risks of maintaining lower blood oxygen levels are unclear at this time, which is why this study is needed. Answering this question will help improve the future treatment of children in intensive care. If critically ill children on intensive care can be managed safely with slightly lower oxygen saturations, they might need less intensive treatment and may recover more quickly.
Where is the study run from?
Great Ormond Street Hospital for Children NHS Foundation Trust (UK)
When is the study starting and how long is it expected to run for?
August 2019 to July 2023
Who is funding the study?
National Institute for Health Research (NIHR) (UK)
Who is the main contact?
1. Mrs Daisy Wiley
daisy.wiley@icnarc.org
2. Prof. Mark Peters
mark.peters@ucl.ac.uk
Trial website
Contact information
Type
Public
Primary contact
Mrs Daisy Wiley
ORCID ID
Contact details
ICNARC
Napier House
24 High Holborn
London
WC1V 6AZ
United Kingdom
+44 (0)20 7831 6879
daisy.wiley@icnarc.org
Type
Scientific
Additional contact
Prof Mark Peters
ORCID ID
http://orcid.org/0000-0003-3653-4808
Contact details
UCL Great Ormond Street Institute of Child Health
30 Guilford Street
Holborn
London
WC1N 1EH
United Kingdom
-
mark.peters@ucl.ac.uk
Additional identifiers
EudraCT number
Nil known
ClinicalTrials.gov number
Nil known
Protocol/serial number
CPMS 44070, IRAS 272768
Study information
Scientific title
A randomised multiple centre trial of conservative versus liberal oxygenation targets in critically ill children (Oxy-PICU)
Acronym
Oxy-PICU RCT
Study hypothesis
Oxy-PICU is a multiple centre open, parallel-group, randomised control trial (RCT) with integrated economic analysis. An RCT design was chosen as this is the gold standard design for clinical trials.
Oxy-PICU aims to identify the best oxygen range to target in critically ill children to improve patient outcomes, with the hypothesis that a more conservative approach to oxygenation is superior to the more liberal approach often currently used.
Ethics approval
Approved 23/12/2019, East of England – Cambridge South (Tel: +44 (0)207 104 8134; Email: Nrescommitee.eastofengland-cambridgesouth@nhs.net), ref: 19/EE/0362
Study design
Randomised; Interventional; Design type: Treatment, Other
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
See additional files
Condition
Critical care
Intervention
The researchers will recruit 2040 patients from 15 paediatric critical care units and their associated specialist retrieval services (teams of doctors and nurses that attend local hospitals to assist with the specialist care of critically ill children and their ambulance transportation to a regional, specialist paediatric intensive care unit).
The study will use a deferred consent model due to the emergency nature of the patient population. Eligible patients will be randomised by the PICU or the retrieval teams and their parents or legal guardians will be approached for consent to continue in the study at the earliest appropriate opportunity.
Whilst mortality is the most important outcome measure, it is challenging to adequately power a study on mortality alone within paediatrics. The researchers have therefore used information from qualitative work to inform a composite outcome. This work highlighted the child 'looking and feeling more like themselves' as the most important outcome measure for parents. The researchers will therefore use a combination of mortality (worst possible outcome) and days on organ support as the primary outcome.
Once recruitment is completed, an equal number of children will have been allocated to each treatment group:
Liberal group (greater than or equal to 95% blood oxygen)
Participants allocated to this group will receive supplement oxygen and ventilator settings at the discretion of the treating clinical team with the aim of peripheral oxygen saturations remaining at or above 95%. This will be continued until invasive mechanical ventilation is discontinued or PICU discharge, whichever is sooner.
Conservative group (88-92% blood oxygen)
Participants allocated to the conservative group will receive supplemental oxygen and ventilator settings at the discretion of the treating clinical team with the aim of peripheral oxygen saturations remaining 88-92% (inclusive). This will be continued until invasive mechanical ventilation is discontinued or PICU discharge, whichever is sooner. All other clinical care for patients in both treatment groups will be determined by the clinical team responsible for the patients care.
Data will be collected daily whilst in PICU to describe the intensity and duration of treatment, alongside routine data collection. Patients will be followed up after one year to ascertain their quality of life. One interim analysis will be undertaken.
An internal pilot will be conducted to assess key progression criteria in relation to site opening, recruitment and adherence to the protocol. The internal pilot will follow the same processes as the main trial and participants enrolled in the pilot will be included in the analysis of the main RCT. At the end of the internal pilot, the Trial Steering Committee will make a recommendation to the funder as to whether they feel the trial should continue. The funder will take the final decision.
Following the end of recruitment, analysis of the study data will take place and articles will be prepared for publication. It will not be possible to identify any participants in any publications.
Intervention type
Other
Phase
Drug names
Primary outcome measure
1. A composite of mortality and days of organ support at 30 days assessed through review of patient medical notes and/or data-linkage with nationally held death registrations (clinical effectiveness)
2. Incremental costs, quality-adjusted life years and net monetary benefit assessed using age-appropriate Pediatric Quality of Life Inventory (Peds-QL) and the Child Health Utility 9D (CHU-9D) at 12 months (cost effectiveness)
Secondary outcome measures
1. Mortality assessed via patient medical notes and/or data linkage with nationally held death registrations at PICU discharge, 30 days, 90 days and 12 months
2. Time to liberation from mechanical ventilation defined as the time the child was extubated and remained so for the remainder of their PICU stay
3. Duration of organ support during the child’s PICU stay
4. Duration of PICU and hospital stay assessed through review of patient medical notes at PICU discharge and hospital discharge
Overall trial start date
01/08/2019
Overall trial end date
01/07/2023
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Age > 38 weeks corrected gestational age and < 16 years
2. Unplanned PICU referral
3. Commenced on invasive mechanical ventilation with supplemental oxygen
4. Within 6 hours of face-to-face contact with PICU staff or retrieval team
Participant type
Patient
Age group
Child
Gender
Both
Target number of participants
Planned Sample Size: 2040; UK Sample Size: 2040
Participant exclusion criteria
1. Death perceived as imminent
2. Brain pathology/injury as primary reason for admission
3. Known pulmonary hypertension
4. Known or suspected uncorrected congenital cardiac disease
5. Known sickle cell disease
6. End-of-life care plan in place with limitation of resuscitation
7. Receiving long-term mechanical ventilation prior to this admission
8. Recruited to Oxy-PICU in a previous admission
Recruitment start date
01/02/2020
Recruitment end date
31/01/2022
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Great Ormond Street Hospital For Children NHS Foundation Trust
Great Ormond Street
London
WC1N 3JH
United Kingdom
Sponsor information
Organisation
Intensive Care National Audit and Research Centre (ICNARC)
Sponsor details
c/o Keji Dalemo
Napier House
24 High Holborn
London
WC1V 6AZ
United Kingdom
+44 (0)2072699277
keji.dalemo@icnarc.org
Sponsor type
Research organisation
Website
Funders
Funder type
Government
Funder name
NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC); Grant Codes: NIHR127547
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
National Institute for Health Research (NIHR) (UK)
Alternative name(s)
NIHR
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
1. The protocol will be publicly available on the ICNARC and NIHR website
2. A protocol paper will be written and published (expected June 2020)
3. A statistical analysis plan paper will be written and publish (expected February 2021)
4. Peer-reviewed scientific journals
5. Conference presentation
6. Publication on website
IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date
Intention to publish date
01/07/2024
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list
Publication citations
Additional files
- ISRCTN92103439_PIS_v1.1_18Dec19.pdf Uploaded 07/01/2020