Clinical trial NCT03040570: Conservative Versus Liberal Oxygenation Targets in Critically Ill Children
Official title: A Randomised Pilot Multiple Centre Trial of Conservative Versus Liberal Oxygenation Targets in Critically Ill Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Critical Care
Hypoxia
Pediatric ALL
Lead sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Intensive Care National Audit & Research Centre
name: University of Southampton
name: St Mary's Hospital, London
name: University Hospital Southampton NHS Foundation Trust
name: University College, London
First posted: 2017-02-02
Enrollment: 120
Sex: ALL
Minimum age (years): 39
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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).

Eligibility criteria: 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)

Primary outcomes:
measure: Number of eligible patients recruited per site per month
timeFrame: Baseline
Secondary outcomes:
measure: Proportion of parents/legal representatives refusing deferred consent
timeFrame: Through study completion, an average of 24 hours
measure: Proportion of eligible patients randomised
timeFrame: Baseline
measure: Distribution of time to randomisation
timeFrame: Baseline
measure: Proportion of systemic oxygen saturations within the target range in each group
timeFrame: Through study completion, an average of 72 hours
measure: Proportion of patients in each arm requiring other treatments influencing tissue oxygen delivery (blood transfusion, inotropic support)
timeFrame: Through study completion, an average of 72 hours
measure: Length of ventilation - proportion of randomised patients with outcome available in each group
timeFrame: Through study completion, an average of 2 days
measure: Length of ventilation - mean (standard deviation) in each group
timeFrame: Through study completion, an average of 2 days
measure: Length of ventilation - median and quartiles in each group.
timeFrame: Through study completion, an average of 2 days
measure: Observed adverse events
timeFrame: 28 days
measure: Time taken for data collection and entry
timeFrame: 28 days
measure: Measurement of ischemia-modified albumin (plasma)
timeFrame: 72 hours
measure: Measurement of malondialdehyde (plasma)
timeFrame: 72 hours
measure: Measurement of total antioxidant status (plasma)
timeFrame: 72 hours
measure: Length of PICU stay - proportion of randomised patients with outcome available in each group
timeFrame: Through study completion, an average of 2 days
measure: Length of PICU stay - mean (standard deviation) in each group.
timeFrame: Through study completion, an average of 2 days
measure: Length of PICU stay - median and quartiles in each group.
timeFrame: Through study completion, an average of 2 days
measure: Hospital mortality - proportion of randomised patients with outcome available in each group
timeFrame: Through study completion, an average of 2 days
measure: Hospital mortality - number (percentage) in each group.
timeFrame: Through study completion, an average of 2 days
measure: PICU mortality - proportion of randomised patients with outcome available in each group
timeFrame: Through study completion, an average of 2 days
measure: PICU mortality - number (percentage) in each group.
timeFrame: Through study completion, an average of 2 days
measure: Days of organ specific support - proportion of randomised patients with outcome available in each group
timeFrame: Through study completion, an average of 2 days
measure: Days of organ specific support - mean (standard deviation) in each group
timeFrame: Through study completion, an average of 2 days
measure: Days of organ specific support - median and quartiles in each group
timeFrame: Through study completion, an average of 2 days
measure: Measurement of hypoxia-inducible factor-1 alpha mRNA expression (leukocytes)
timeFrame: 72 hours
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children
city: London
country: United Kingdom
facility: St Mary's Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
References:
citation: Peters MJ, Jones GAL, Wiley D, Wulff J, Ramnarayan P, Ray S, Inwald D, Grocott M, Griksaitis M, Pappachan J, O'Neill L, Eaton S, Mouncey PR, Harrison DA, Rowan KM; Oxy-PICU Investigators for the Paediatric Intensive Care Society Study Group (PICS-SG). Conservative versus liberal oxygenation targets in critically ill children: the randomised multiple-centre pilot Oxy-PICU trial. Intensive Care Med. 2018 Aug;44(8):1240-1248. doi: 10.1007/s00134-018-5232-7. Epub 2018 Jun 4.
citation: Jones GAL, Ramnarayan P, Raman S, Inwald D, Grocott MPW, Eaton S, Ray S, Griksaitis MJ, Pappachan J, Wiley D, Mouncey PR, Wulff J, Harrison DA, Rowan KM, Peters MJ; Oxy-PICU Investigators for thePaediatric Intensive Care Society-Study Group (PICS-SG). Protocol for a randomised pilot multiple centre trial of conservative versus liberal oxygenation targets in critically ill children (Oxy-PICU). BMJ Open. 2017 Dec 14;7(12):e019253. doi: 10.1136/bmjopen-2017-019253.