A randomised multiple centre trial of conservative versus liberal oxygenation targets in critically ill children (Oxy-PICU)

ISRCTN	ISRCTN92103439
DOI	https://doi.org/10.1186/ISRCTN92103439
IRAS number	272768
Secondary identifying numbers	CPMS 44070, IRAS 272768

Submission date: 06/01/2020
Registration date: 07/01/2020
Last edited: 20/12/2024

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Other

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

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 years 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 September 2023

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

Who is the main contact?
1. Paul Mouncey, oxypicu@icnarc.org
(updated 20/07/2020, previously: Mrs Daisy Wiley, daisy.wiley@icnarc.org)
2. Prof. Mark Peters, mark.peters@ucl.ac.uk

Study website

Contact information

Mr Paul Mouncey
Public

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

Phone	+44 (0)20 7831 6879
Email	oxypicu@icnarc.org

Prof Mark Peters
Scientific

UCL Great Ormond Street Institute of Child Health
30 Guilford Street
Holborn
London
WC1N 1EH
United Kingdom

ORCID ID	0000-0003-3653-4808
Email	mark.peters@ucl.ac.uk

Study information

Study design	Randomized; Interventional; Design type: Treatment, Other
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	ISRCTN92103439_PIS_v1.1_18Dec19.pdf
Scientific title	A randomised multiple centre trial of conservative versus liberal oxygenation targets in critically ill children (Oxy-PICU)
Study acronym	Oxy-PICU RCT
Study objectives	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(s)	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
Health condition(s) or problem(s) studied	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
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	Current secondary outcome measures as of 09/11/2022: 1. Incremental costs calculated from patient-level resource data, length of stay in PICU/HDU and acute hospital for the index admission and any re-admission before 30 days after randomisation 2. 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 3. Time to liberation from mechanical ventilation, defined as the time the child was extubated and remained so for the remainder of their PICU stay 4. Duration of organ support during the child’s PICU stay 5. Functional status at PICU discharge as assessed by a clinician using the Paediatric Cerebral Performance Category (PCPC) and Paediatric Overall Performance Category (POPC) scales using patient’s notes 6. Duration of PICU and hospital stay assessed through review of patient medical notes at PICU discharge and hospital discharge 7. HrQoL at 12 months, measured by the child, self-or parent-proxy reported PedsQL-4.0 and the Child Heath Utility 9D (CHU-9D) at 12 months post randomisation Previous 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 study start date	01/08/2019
Completion date	30/09/2023

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	38 Weeks
Upper age limit	16 Years
Sex	Both
Target number of participants	Planned Sample Size: 2040; UK Sample Size: 2040
Total final enrolment	2040
Key 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
Key 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
Date of first enrolment	01/02/2020
Date of final enrolment	23/05/2022

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Great Ormond Street Hospital For Children NHS Foundation Trust

Great Ormond Street
London
WC1N 3JH
United Kingdom

Sponsor information

Intensive Care National Audit and Research Centre (ICNARC)
Research organisation

c/o Paul Mouncey
Napier House
24 High Holborn
London
WC1V 6AZ
England
United Kingdom

Phone	+44 (0)2072699277
Email	paul.mouncey@icnarc.org
"ROR"	https://ror.org/057b2ek35

Funders

Funder type

Government

NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC); Grant Codes: NIHR127547

No information available

National Institute for Health Research (NIHR) (UK)
Government organisation / National government

Alternative name(s): National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
Location: United Kingdom

Results and Publications

Intention to publish date	31/01/2024
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
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 plan	The datasets generated during and/or analysed during the current study are/will be available upon request from the Chief Investigator, Prof. Mark Peters (mark.peters@ucl.ac.uk). Application requests to access anonymised data for scientific research may be granted following review and approval by the Chief Investigator and the ICNARC CTU.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	version v1.1	18/12/2019	07/01/2020	No	Yes
Other publications	Mechanistic substudy nested within the Oxy-PICU study	19/01/2023	01/03/2023	Yes	No
Protocol article	Protocol	01/09/2022	01/03/2023	Yes	No
Statistical Analysis Plan	version 1.2		01/03/2023	No	No
HRA research summary			20/09/2023	No	No
Results article		01/12/2023	05/12/2023	Yes	No
Results article		17/12/2024	20/12/2024	Yes	No

Additional files

ISRCTN92103439_PIS_v1.1_18Dec19.pdf: Uploaded 07/01/2020
ISRCTN92103439_SAP_v1.2_29Nov2022.pdf

Editorial Notes

20/12/2024: Publication reference added.
15/01/2024: IPD sharing plan added.
05/12/2023: Publication reference added.
09/11/2023: The intention to publish date was changed from 30/09/2023 to 31/01/2024.
20/09/2023: A link to the HRA research summary was added.
16/08/2023: The following changes were made to the trial record:
1. The total final enrolment was added.
2. The intention to publish date was changed from 31/08/2023 to 30/09/2023.
23/06/2023: The intention to publish date was changed from 01/06/2023 to 31/08/2023.
01/03/2023: The following changes were made to the trial record:
1. Two publication references were added.
2. Uploaded statistical analysis plan.
3. The intention to publish date has been changed from 01/07/2024 to 01/06/2023.
4. The sponsor contact was updated.
09/11/2022: The following changes were made to the trial record:
1. The recruitment end date has been changed from 30/05/2022 to 23/05/2022.
2. The secondary outcome measures have been changed.
12/05/2022: The overall trial end date has been changed from 01/07/2023 to 30/09/2023 and the plain English summary updated accordingly.
04/04/2022: The recruitment end date was changed from 30/04/2022 to 30/05/2022.
02/03/2022: The recruitment end date was changed from 31/03/2022 to 30/04/2022.
10/01/2022: The recruitment end date was changed from 31/01/2022 to 31/03/2022. Trial website added.
20/07/2020: The following changes were made to the trial record:
1. The public contact was changed.
2. The plain English summary was updated to reflect these changes.
07/01/2020: Trial's existence confirmed by the NIHR. The participant information sheet has been uploaded.