Conservative Versus Liberal Oxygenation Targets in Critically Ill Children

Study Overview
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Brief Summary
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A feasibility study to determine if it is possible to perform a safe, adequately powered, and affordable multi-centre study in critically ill children comparing current practice of liberal targets for systemic oxygen levels with more conservative targets.

Detailed Description
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Around 19,000 critically ill children are admitted to paediatric intensive care units (PICU) each year in the UK. A large number of these children need breathing support, and this is usually provided through an invasive machine called a 'ventilator'. Clinicians make decisions for treatment based on how much oxygen their patient has in their blood (this is called oxygen saturation or oxygenation) and currently the amount of oxygen critically ill children need is not fully understood. This means that some clinicians use a lower oxygen saturation target, and others, a higher target. This may be problematic as research in neonates (babies) and adults has shown that oxygen saturation levels can influence a patient's chance of survival, how long they stay in hospital and healthcare costs. Response to oxygen is different in babies, children and adults. This means that the results from the neonatal and adult research are unlikely to be valid or applicable in children due to age-related differences. Urgent high quality clinical evidence is therefore needed to inform on the best targets of oxygenation during critical illness in children. As large clinical trials are expensive to conduct, it is important to demonstrate that a large-scale trial can be done and that the different components of a trial can all work together. Therefore, the Oxy-PICU study is a 'pilot randomised clinical trial' (a smaller version of the trial we would like to conduct) and will test the feasibility and safety of conducting a large scale trial comparing a restrictive oxygen saturation target (88-92%) with a more liberal oxygen saturation target (>94%). Oxy-PICU will also collect blood and urine samples to allow for in depth study of the biology of the different oxygenation targets. The pilot trial will take place at three PICUs (two in London and one in Southampton) and aims to include between 115-125 eligible children over six months. Given the emergency nature of these children and the need to provide immediate care, informed consent will be sought after the children are entered into the study (this is known as deferred consent).

Official Title
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A Randomised Pilot Multiple Centre Trial of Conservative Versus Liberal Oxygenation Targets in Critically Ill Children

Conditions
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Hypoxia, Critical Care, Pediatric ALL

Intervention / Treatment
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* Procedure: Conservative oxygenation target
* Procedure: Liberal oxygenation target


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: less than 16 years and > 38 weeks corrected gestational age receiving supplemental oxygen for abnormal gas exchange emergency admission accepted to a participating paediatric intensive care unit (PICU) requiring mechanical ventilation within first 6 hours of face-to-face contact with PICU staff or transport team Exclusion Criteria: recruited to Oxy-PICU in a previous admission brain pathology/injury as a primary reason for admission (e.g traumatic brain injury, post-cardiac arrest, stroke, convulsive status epilepticus without aspiration) known pulmonary hypertension known or suspected sickle cell disease known or suspected uncorrected congenital cardiac disease End-of-life care plan in place with limitation of resuscitation not expected to survive PICU admission receiving long-term mechanical ventilation prior to this admission (non-invasive ventilation or invasive ventilation)

Ages Eligible for Study
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Minimum Age: 39 Weeks
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Conservative oxygenation target<br>Children in the conservative oxygenation target group receive treatment targeting oxygen saturation values of 88-92%. | Procedure: Conservative oxygenation target<br>* Participants allocated to the conservative oxygenation target 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).<br>|
| Active Comparator: Liberal oxygenation target<br>Children in the liberal oxygenation target group receive treatment targeting oxygen saturation values of >94%. | Procedure: Liberal oxygenation target<br>* Participants allocated to the liberal oxygenation target group will receive supplemental oxygen and ventilator settings at the discretion of the treating clinical team with the aim of peripheral oxygen saturations remaining >94%.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of eligible patients recruited per site per month |  | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of parents/legal representatives refusing deferred consent |  | Through study completion, an average of 24 hours | 
| Proportion of eligible patients randomised |  | Baseline | 
| Distribution of time to randomisation |  | Baseline | 
| Proportion of systemic oxygen saturations within the target range in each group |  | Through study completion, an average of 72 hours | 
| Proportion of patients in each arm requiring other treatments influencing tissue oxygen delivery (blood transfusion, inotropic support) |  | Through study completion, an average of 72 hours | 
| Length of ventilation - proportion of randomised patients with outcome available in each group |  | Through study completion, an average of 2 days | 
| Length of ventilation - mean (standard deviation) in each group |  | Through study completion, an average of 2 days | 
| Length of ventilation - median and quartiles in each group. |  | Through study completion, an average of 2 days | 
| Observed adverse events |  | 28 days | 
| Time taken for data collection and entry |  | 28 days | 
| Measurement of ischemia-modified albumin (plasma) |  | 72 hours | 
| Measurement of malondialdehyde (plasma) |  | 72 hours | 
| Measurement of total antioxidant status (plasma) |  | 72 hours | 
| Length of PICU stay - proportion of randomised patients with outcome available in each group |  | Through study completion, an average of 2 days | 
| Length of PICU stay - mean (standard deviation) in each group. |  | Through study completion, an average of 2 days | 
| Length of PICU stay - median and quartiles in each group. |  | Through study completion, an average of 2 days | 
| Hospital mortality - proportion of randomised patients with outcome available in each group |  | Through study completion, an average of 2 days | 
| Hospital mortality - number (percentage) in each group. |  | Through study completion, an average of 2 days | 
| PICU mortality - proportion of randomised patients with outcome available in each group |  | Through study completion, an average of 2 days | 
| PICU mortality - number (percentage) in each group. |  | Through study completion, an average of 2 days | 
| Days of organ specific support - proportion of randomised patients with outcome available in each group |  | Through study completion, an average of 2 days | 
| Days of organ specific support - mean (standard deviation) in each group |  | Through study completion, an average of 2 days | 
| Days of organ specific support - median and quartiles in each group |  | Through study completion, an average of 2 days | 
| Measurement of hypoxia-inducible factor-1 alpha mRNA expression (leukocytes) |  | 72 hours |