Condition category
Not Applicable
Date applied
06/01/2020
Date assigned
07/01/2020
Last edited
20/07/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

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. 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

Trial website

Contact information

Type

Public

Primary contact

Mr Paul Mouncey

ORCID ID

Contact details

ICNARC
Napier House
24 High Holborn
London
WC1V 6AZ
United Kingdom
+44 (0)20 7831 6879
oxypicu@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

Editorial Notes

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.