<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03040570</url>
  </required_header>
  <id_info>
    <org_study_id>15IA35</org_study_id>
    <nct_id>NCT03040570</nct_id>
  </id_info>
  <brief_title>Conservative Versus Liberal Oxygenation Targets in Critically Ill Children</brief_title>
  <acronym>Oxy-PICU</acronym>
  <official_title>A Randomised Pilot Multiple Centre Trial of Conservative Versus Liberal Oxygenation Targets in Critically Ill Children</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Great Ormond Street Hospital for Children NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Intensive Care National Audit &amp; Research Centre</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Southampton</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>St Mary's Hospital, London</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital Southampton NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University College, London</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Great Ormond Street Hospital for Children NHS Foundation Trust</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A feasibility study to determine if it is possible to perform a safe, adequately powered, and&#xD;
      affordable multi-centre study in critically ill children comparing current practice of&#xD;
      liberal targets for systemic oxygen levels with more conservative targets.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Around 19,000 critically ill children are admitted to paediatric intensive care units (PICU)&#xD;
      each year in the UK. A large number of these children need breathing support, and this is&#xD;
      usually provided through an invasive machine called a 'ventilator'. Clinicians make decisions&#xD;
      for treatment based on how much oxygen their patient has in their blood (this is called&#xD;
      oxygen saturation or oxygenation) and currently the amount of oxygen critically ill children&#xD;
      need is not fully understood. This means that some clinicians use a lower oxygen saturation&#xD;
      target, and others, a higher target. This may be problematic as research in neonates (babies)&#xD;
      and adults has shown that oxygen saturation levels can influence a patient's chance of&#xD;
      survival, how long they stay in hospital and healthcare costs.&#xD;
&#xD;
      Response to oxygen is different in babies, children and adults. This means that the results&#xD;
      from the neonatal and adult research are unlikely to be valid or applicable in children due&#xD;
      to age-related differences. Urgent high quality clinical evidence is therefore needed to&#xD;
      inform on the best targets of oxygenation during critical illness in children.&#xD;
&#xD;
      As large clinical trials are expensive to conduct, it is important to demonstrate that a&#xD;
      large-scale trial can be done and that the different components of a trial can all work&#xD;
      together. Therefore, the Oxy-PICU study is a 'pilot randomised clinical trial' (a smaller&#xD;
      version of the trial we would like to conduct) and will test the feasibility and safety of&#xD;
      conducting a large scale trial comparing a restrictive oxygen saturation target (88-92%) with&#xD;
      a more liberal oxygen saturation target (&gt;94%). Oxy-PICU will also collect blood and urine&#xD;
      samples to allow for in depth study of the biology of the different oxygenation targets.&#xD;
&#xD;
      The pilot trial will take place at three PICUs (two in London and one in Southampton) and&#xD;
      aims to include between 115-125 eligible children over six months. Given the emergency nature&#xD;
      of these children and the need to provide immediate care, informed consent will be sought&#xD;
      after the children are entered into the study (this is known as deferred consent).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 4, 2017</start_date>
  <completion_date type="Actual">July 1, 2017</completion_date>
  <primary_completion_date type="Actual">June 25, 2017</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of eligible patients recruited per site per month</measure>
    <time_frame>Baseline</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of parents/legal representatives refusing deferred consent</measure>
    <time_frame>Through study completion, an average of 24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of eligible patients randomised</measure>
    <time_frame>Baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Distribution of time to randomisation</measure>
    <time_frame>Baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of systemic oxygen saturations within the target range in each group</measure>
    <time_frame>Through study completion, an average of 72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients in each arm requiring other treatments influencing tissue oxygen delivery (blood transfusion, inotropic support)</measure>
    <time_frame>Through study completion, an average of 72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of ventilation - proportion of randomised patients with outcome available in each group</measure>
    <time_frame>Through study completion, an average of 2 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of ventilation - mean (standard deviation) in each group</measure>
    <time_frame>Through study completion, an average of 2 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of ventilation - median and quartiles in each group.</measure>
    <time_frame>Through study completion, an average of 2 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Observed adverse events</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time taken for data collection and entry</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measurement of ischemia-modified albumin (plasma)</measure>
    <time_frame>72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measurement of malondialdehyde (plasma)</measure>
    <time_frame>72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measurement of total antioxidant status (plasma)</measure>
    <time_frame>72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of PICU stay - proportion of randomised patients with outcome available in each group</measure>
    <time_frame>Through study completion, an average of 2 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of PICU stay - mean (standard deviation) in each group.</measure>
    <time_frame>Through study completion, an average of 2 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of PICU stay - median and quartiles in each group.</measure>
    <time_frame>Through study completion, an average of 2 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital mortality - proportion of randomised patients with outcome available in each group</measure>
    <time_frame>Through study completion, an average of 2 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital mortality - number (percentage) in each group.</measure>
    <time_frame>Through study completion, an average of 2 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PICU mortality - proportion of randomised patients with outcome available in each group</measure>
    <time_frame>Through study completion, an average of 2 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PICU mortality - number (percentage) in each group.</measure>
    <time_frame>Through study completion, an average of 2 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days of organ specific support - proportion of randomised patients with outcome available in each group</measure>
    <time_frame>Through study completion, an average of 2 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days of organ specific support - mean (standard deviation) in each group</measure>
    <time_frame>Through study completion, an average of 2 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days of organ specific support - median and quartiles in each group</measure>
    <time_frame>Through study completion, an average of 2 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measurement of hypoxia-inducible factor-1 alpha mRNA expression (leukocytes)</measure>
    <time_frame>72 hours</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">120</enrollment>
  <condition>Critical Care</condition>
  <condition>Hypoxia</condition>
  <condition>Pediatric ALL</condition>
  <arm_group>
    <arm_group_label>Conservative oxygenation target</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Children in the conservative oxygenation target group receive treatment targeting oxygen saturation values of 88-92%.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Liberal oxygenation target</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Children in the liberal oxygenation target group receive treatment targeting oxygen saturation values of &gt;94%.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Conservative oxygenation target</intervention_name>
    <description>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).</description>
    <arm_group_label>Conservative oxygenation target</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Liberal oxygenation target</intervention_name>
    <description>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 &gt;94%.</description>
    <arm_group_label>Liberal oxygenation target</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  less than 16 years and &gt; 38 weeks corrected gestational age&#xD;
&#xD;
          -  receiving supplemental oxygen for abnormal gas exchange&#xD;
&#xD;
          -  emergency admission accepted to a participating paediatric intensive care unit (PICU)&#xD;
             requiring mechanical ventilation within first 6 hours of face-to-face contact with&#xD;
             PICU staff or transport team&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  recruited to Oxy-PICU in a previous admission&#xD;
&#xD;
          -  brain pathology/injury as a primary reason for admission (e.g traumatic brain injury,&#xD;
             post-cardiac arrest, stroke, convulsive status epilepticus without aspiration)&#xD;
&#xD;
          -  known pulmonary hypertension&#xD;
&#xD;
          -  known or suspected sickle cell disease&#xD;
&#xD;
          -  known or suspected uncorrected congenital cardiac disease&#xD;
&#xD;
          -  End-of-life care plan in place with limitation of resuscitation&#xD;
&#xD;
          -  not expected to survive PICU admission&#xD;
&#xD;
          -  receiving long-term mechanical ventilation prior to this admission (non-invasive&#xD;
             ventilation or invasive ventilation)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>39 Weeks</minimum_age>
    <maximum_age>15 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Great Ormond Street Hospital for Children</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Mary's Hospital</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southampton General Hospital</name>
      <address>
        <city>Southampton</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>February 2018</verification_date>
  <study_first_submitted>November 21, 2016</study_first_submitted>
  <study_first_submitted_qc>January 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 2, 2017</study_first_posted>
  <last_update_submitted>February 22, 2018</last_update_submitted>
  <last_update_submitted_qc>February 22, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 23, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypoxia</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03040570
org study id: 15IA35
nct id: NCT03040570
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
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).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of eligible patients recruited per site per month
time frame: Baseline
measure: Proportion of parents/legal representatives refusing deferred consent
time frame: Through study completion, an average of 24 hours
measure: Proportion of eligible patients randomised
time frame: Baseline
measure: Distribution of time to randomisation
time frame: Baseline
measure: Proportion of systemic oxygen saturations within the target range in each group
time frame: 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)
time frame: Through study completion, an average of 72 hours
measure: Length of ventilation - proportion of randomised patients with outcome available in each group
time frame: Through study completion, an average of 2 days
measure: Length of ventilation - mean (standard deviation) in each group
time frame: Through study completion, an average of 2 days
measure: Length of ventilation - median and quartiles in each group.
time frame: Through study completion, an average of 2 days
measure: Observed adverse events
time frame: 28 days
measure: Time taken for data collection and entry
time frame: 28 days
measure: Measurement of ischemia-modified albumin (plasma)
time frame: 72 hours
measure: Measurement of malondialdehyde (plasma)
time frame: 72 hours
measure: Measurement of total antioxidant status (plasma)
time frame: 72 hours
measure: Length of PICU stay - proportion of randomised patients with outcome available in each group
time frame: Through study completion, an average of 2 days
measure: Length of PICU stay - mean (standard deviation) in each group.
time frame: Through study completion, an average of 2 days
measure: Length of PICU stay - median and quartiles in each group.
time frame: Through study completion, an average of 2 days
measure: Hospital mortality - proportion of randomised patients with outcome available in each group
time frame: Through study completion, an average of 2 days
measure: Hospital mortality - number (percentage) in each group.
time frame: Through study completion, an average of 2 days
measure: PICU mortality - proportion of randomised patients with outcome available in each group
time frame: Through study completion, an average of 2 days
measure: PICU mortality - number (percentage) in each group.
time frame: Through study completion, an average of 2 days
measure: 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
measure: Days of organ specific support - mean (standard deviation) in each group
time frame: Through study completion, an average of 2 days
measure: Days of organ specific support - median and quartiles in each group
time frame: Through study completion, an average of 2 days
measure: Measurement of hypoxia-inducible factor-1 alpha mRNA expression (leukocytes)
time frame: 72 hours
arm group label: Conservative oxygenation target
arm group type: Experimental
description: Children in the conservative oxygenation target group receive treatment targeting oxygen saturation values of 88-92%.
arm group label: Liberal oxygenation target
arm group type: Active Comparator
description: Children in the liberal oxygenation target group receive treatment targeting oxygen saturation values of >94%.
intervention type: Procedure
intervention name: Conservative oxygenation target
description: 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).
arm group label: Conservative oxygenation target
intervention type: Procedure
intervention name: Liberal oxygenation target
description: 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 group label: Liberal oxygenation target
criteria: 
gender: All
minimum age: 39 Weeks
maximum age: 15 Years
healthy volunteers: No
facility: 
facility: 
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Hypoxia