Conservative Versus Liberal Oxygenation Targets in Critically Ill Children

ID: NCT03040570
Status: Completed
Phase: N/A
Start Date: March 04, 2017
First Submitted: November 21, 2016
Last Updated: February 22, 2018
Results: N/A
Sponsors & Collaborators: Great Ormond Street Hospital for Children NHS Foundation Trust, Intensive Care National Audit & Research Centre, University of Southampton and 5 more..
Location: United Kingdom
Conditions: Critical Care, Hypoxia, Pediatric ALL
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Study Description

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).
Condition or disease Intervention/treatment Phase

Critical Care

Hypoxia

Pediatric ALL

Procedure: Conservative oxygenation target
Other Names
Procedure: Liberal oxygenation target
Other Names
N/A

Tracking Information

First Submitted DateNovember 21, 2016
Last Update Posted DateFebruary 22, 2018
Actual Start DateMarch 04, 2017
Actual Completion DateJuly 01, 2017
Actual Primary Completion DateJune 25, 2017
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Number of eligible patients recruited per site per month [Time Frame: Baseline]

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Proportion of parents/legal representatives refusing deferred consent [Time Frame: Through study completion, an average of 24 hours]

  • Proportion of eligible patients randomised [Time Frame: Baseline]

  • Distribution of time to randomisation [Time Frame: Baseline]

  • Proportion of systemic oxygen saturations within the target range in each group [Time Frame: 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) [Time Frame: Through study completion, an average of 72 hours]

  • Length of ventilation - proportion of randomised patients with outcome available in each group [Time Frame: Through study completion, an average of 2 days]

  • Length of ventilation - mean (standard deviation) in each group [Time Frame: Through study completion, an average of 2 days]

  • Length of ventilation - median and quartiles in each group. [Time Frame: Through study completion, an average of 2 days]

  • Observed adverse events [Time Frame: 28 days]

  • Time taken for data collection and entry [Time Frame: 28 days]

  • Measurement of ischemia-modified albumin (plasma) [Time Frame: 72 hours]

  • Measurement of malondialdehyde (plasma) [Time Frame: 72 hours]

  • Measurement of total antioxidant status (plasma) [Time Frame: 72 hours]

  • Length of PICU stay - proportion of randomised patients with outcome available in each group [Time Frame: Through study completion, an average of 2 days]

  • Length of PICU stay - mean (standard deviation) in each group. [Time Frame: Through study completion, an average of 2 days]

  • Length of PICU stay - median and quartiles in each group. [Time Frame: Through study completion, an average of 2 days]

  • Hospital mortality - proportion of randomised patients with outcome available in each group [Time Frame: Through study completion, an average of 2 days]

  • Hospital mortality - number (percentage) in each group. [Time Frame: Through study completion, an average of 2 days]

  • PICU mortality - proportion of randomised patients with outcome available in each group [Time Frame: Through study completion, an average of 2 days]

  • PICU mortality - number (percentage) in each group. [Time Frame: Through study completion, an average of 2 days]

  • Days of organ specific support - proportion of randomised patients with outcome available in each group [Time Frame: Through study completion, an average of 2 days]

  • Days of organ specific support - mean (standard deviation) in each group [Time Frame: Through study completion, an average of 2 days]

  • Days of organ specific support - median and quartiles in each group [Time Frame: Through study completion, an average of 2 days]

  • Measurement of hypoxia-inducible factor-1 alpha mRNA expression (leukocytes) [Time Frame: 72 hours]

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleConservative Versus Liberal Oxygenation Targets in Critically Ill Children
Official TitleA Randomised Pilot Multiple Centre Trial of Conservative Versus Liberal Oxygenation Targets in Critically Ill Children
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).

Study TypeInterventional
Study PhaseN/A
Estimated Enrollment
120
Allocation
Randomized
Interventional Model
Parallel Assignment
Masking
None (Open Label)
Primary Purpose
Treatment
Conditions
Critical Care
Hypoxia
Pediatric ALL
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Procedure: Conservative oxygenation target

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).

Other Names
Procedure: Liberal oxygenation target

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%.

Other Names
Study Groups/Cohorts
Conservative oxygenation target
Children in the conservative oxygenation target group receive treatment targeting oxygen saturation values of 88-92%.

Liberal oxygenation target
Children in the liberal oxygenation target group receive treatment targeting oxygen saturation values of >94%.

Study Arms
Experimental Conservative oxygenation target
Children in the conservative oxygenation target group receive treatment targeting oxygen saturation values of 88-92%.
Procedure : Conservative oxygenation target
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).

Active Comparator Liberal oxygenation target
Children in the liberal oxygenation target group receive treatment targeting oxygen saturation values of >94%.
Procedure : Liberal oxygenation target
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%.

Arm Intervention/Treatment
Experimental Conservative oxygenation target
Children in the conservative oxygenation target group receive treatment targeting oxygen saturation values of 88-92%.
Procedure : Conservative oxygenation target
Active Comparator Liberal oxygenation target
Children in the liberal oxygenation target group receive treatment targeting oxygen saturation values of >94%.
Procedure : Liberal oxygenation target

Recruitment Information

Recruitment Status:Completed
Enrollment120
Completion DateJuly 01, 2017
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)
GenderAll
Age39 Weeks to 15 Years
Accepts Healthy VolunteersNo
Contacts
Not Available
Listed Location Countries
United Kingdom

Administrative Information

NCT Number:NCT03040570
Other Study ID Numbers
15IA35
Has Data Monitoring CommitteeYes
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Great Ormond Street Hospital for Children NHS Foundation Trust
Collaborators
Intensive Care National Audit & Research Centre
University of Southampton
St Mary's Hospital, London
University Hospital Southampton NHS Foundation Trust
University College, London
Investigators
Not Available