<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/NCT02200900</url>
  </required_header>
  <id_info>
    <org_study_id>7022</org_study_id>
    <nct_id>NCT02200900</nct_id>
  </id_info>
  <brief_title>Study of Respiratory Physiology During High Flow Nasal Cannula Treatment in Preterm Neonates.</brief_title>
  <official_title>Study of Nasopharyngeal Pressures, Tidal Breathing Indices and Inspired Gas Concentrations During High Flow Nasal Cannula (HFNC) and CPAP Treatment in Neonates</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Newcastle-upon-Tyne Hospitals NHS Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Newcastle-upon-Tyne Hospitals NHS Trust</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The most commonly used noninvasive respiratory support in preterm babies is Continuous&#xD;
      Positive Airway Pressure (CPAP), which provides extra breathing support to babies who are&#xD;
      breathing by themselves). Increasingly High flow Nasal Cannula (HFNC, newer form of extra&#xD;
      breathing support) therapy has found its way in clinical practice despite lack of good&#xD;
      physiological data. There are also concerns about its potential to generate higher pressures&#xD;
      in airways which can cause over distension of lungs.&#xD;
&#xD;
      We would like to find out the effects of HFNC on&#xD;
&#xD;
        -  1. Airway pressures in various flow rates and in comparison to CPAP.&#xD;
&#xD;
        -  2. Breathing markers including respiratory rate (speed of breathing), oxygen and carbon&#xD;
           dioxide levels, tidal volumes (how much air breathed in with each breath) and airway&#xD;
           wash out (wash out of waste gas from the airway).&#xD;
&#xD;
      We plan to study 15 babies each in three different weight categories supported with either&#xD;
      CPAP or HFNC. The airway pressures, oxygen and carbon dioxide concentration in airway are&#xD;
      measured by a small plastic catheter (similar to feeding tube but much shorter in length),&#xD;
      carbon dioxide levels by skin sensors, how fast and how much babies breathe by a special vest&#xD;
      applied like a layer of clothing. These will be recorded both on HFNC and CPAP. There are no&#xD;
      blood tests or invasive procedures involved. The baby will be monitored throughout the study&#xD;
      period of approximately two hours by experienced registrar who is trained to use the study&#xD;
      device.&#xD;
&#xD;
      This study will improve our understanding of physiological effects of HFNC and lead to better&#xD;
      care of preterm babies.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Purpose and design&#xD;
&#xD;
      Design: Prospective randomised crossover study.&#xD;
&#xD;
      Purpose:&#xD;
&#xD;
        -  Raising airway pressure is one of the most important interventions at the disposal of&#xD;
           clinicians treating patients with respiratory failure. In premature infants Continuous&#xD;
           Positive Airway Pressure (CPAP) and High Flow Nasal Cannula (HFNC) are noninvasive&#xD;
           techniques to raise mean airway pressure when intubation is not required. It is not&#xD;
           clear how clinicians choose between these techniques and there is little data comparing&#xD;
           the physiological effect of these treatments.&#xD;
&#xD;
        -  A composite physiological assessment of babies on HFNC and CPAP treatment is required to&#xD;
           understand how HFNC works. It is important to answer this question to understand how&#xD;
           best to use HFNC in babies.&#xD;
&#xD;
        -  This proposal is designed to provide information on physiological effects of both&#xD;
           therapies in same population of babies across different weight categories. The study&#xD;
           protocol involves use of same HFNC device that is currently being used in neonatal unit.&#xD;
&#xD;
      Interventions:&#xD;
&#xD;
      1. A small plastic catheter tip transducer (Gaeltec) will be placed in upper breathing&#xD;
      passage (nasopharynx or oropharynx) using standard methods. From this we will measure airway&#xD;
      pressures and respiratory gas concentrations.&#xD;
&#xD;
      The catheter will be removed soon after the study is completed. This procedure will be done&#xD;
      once during the study.&#xD;
&#xD;
      2. Breathing markers (Tidal breathing indices) will be measured by non invasive method using&#xD;
      Volusense method where a vest will be applied over the chest and abdomen like a layer of&#xD;
      clothing. The Volusense vest will be removed soon after the procedure. This process is done&#xD;
      once during the study.&#xD;
&#xD;
      3. Blood carbon dioxide (CO2) levels will be measured by a non invasive transcutaneous sensor&#xD;
      applied to the skin (Tosca Radiometer). This skin sensor will be removed soon after the study&#xD;
      is completed.&#xD;
&#xD;
        1. The baby must be clinically stable for preceding 12 hours on noninvasive breathing&#xD;
           support (not meeting exit criteria). The babies will be randomised to either group 1&#xD;
           (CPAP first followed by HFNC) or group 2 (HFNC first followed by CPAP) by computerised&#xD;
           software programme.&#xD;
&#xD;
        2. The measuring devices namely nasopharyngeal catheter, Volusense vest and transcutaneous&#xD;
           CO2 sensor are placed as per standard methods.&#xD;
&#xD;
        3. After ensuring babies' clinical stability the measurements are recorded at HFNC gas flow&#xD;
           rate range from 2 litres to 8 litres per minute and in CPAP of 6 cm of water pressure&#xD;
           level.&#xD;
&#xD;
        4. The study lasts about 2 hours. The baby spends 10 minutes at each HFNC flow rate level&#xD;
           and 30 minutes of equilibration period when support will be changed between HFNC and&#xD;
           CPAP.&#xD;
&#xD;
        5. Routine measurement of heart rate, respiratory rate and oxygen saturations will be done&#xD;
           as per standard neonatal practice. The above data will be recorded electronically for&#xD;
           analysis with total study duration around 120 minutes.&#xD;
&#xD;
        6. Respiratory support can be terminated at any point if clinically not indicated.&#xD;
&#xD;
      The researcher is an experienced neonatal registrar who will be directly observing the baby&#xD;
      throughout the study.&#xD;
&#xD;
      Measurements would be discontinued if any pre set exit criteria is noted.&#xD;
&#xD;
      Statistics: A total of 45 babies (15 babies in each weight category: &lt;1000 grams, 1001500&#xD;
      grams and &gt;1500 grams) will be studied.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>August 2014</start_date>
  <completion_date type="Anticipated">October 2015</completion_date>
  <primary_completion_date type="Anticipated">October 2015</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>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Nasopharyngeal pressures (pressures in upper breathing passages) generated by HFNC at flow rate range of 2 to 8 L/min.</measure>
    <time_frame>Primary outcome recorded during the measurement period of 2 hours.</time_frame>
    <description>The range of pressures generated during high flow nasal cannula treatment over flow rate range of 2 to 8 litres per minute will be recorded during the study period.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Nasopharyngeal pressures (pressures in upper breathing passages) generated at CPAP of 6 cm of water</measure>
    <time_frame>Pressures recorded during the study period of 2 hours</time_frame>
    <description>The nasopharyngeal pressures recorded during CPAP of 6 cm of water pressure will be documented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The effect of changing flow rate of HFNC on following physiological parameters Oxygen saturation and transcutaneous CO2, Respiratory rate, Tidal volume and FRC baseline change.</measure>
    <time_frame>Recorded during the study period of 2 hours</time_frame>
    <description>The physiological parameters including oxygen saturation and transcutaneous CO2, Respiratory rate, Tidal volume and Functional Residual Capacity (FRC) baseline change will be recorded by monitors during the study period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The relationship of flow and inspired oxygen concentration on actual laryngeal inspired and expired O2 and CO2 concentration in HFNC and CPAP.</measure>
    <time_frame>Recorded during the 2 hour study period</time_frame>
    <description>The relationship of flow and inspired oxygen concentration on actual pharyngeal inspired and expired O2 and CO2 concentration in HFNC and CPAP will be noted by gas analyser.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">45</enrollment>
  <condition>Extreme Prematurity - Less Than 28 Weeks</condition>
  <condition>Respiratory Distress Syndrome in Premature Infants</condition>
  <arm_group>
    <arm_group_label>Group 1 ( CPAP followed by HFNC)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>In this group pharyngeal pressure, transcutaneous carbon dioxide concentration, tidal volumes and pharyngeal gas concentrations will be recorded on CPAP first followed by HFNC.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2 (HFNC followed by CPAP)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>In this group pharyngeal pressure, transcutaneous carbon dioxide concentration, tidal volumes and pharyngeal gas concentrations will be recorded on HFNC first followed by CPAP.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Pharyngeal pressure</intervention_name>
    <description>Babies will have pharyngeal pressures measured during the CPAP and HFNC respiratory support.</description>
    <arm_group_label>Group 1 ( CPAP followed by HFNC)</arm_group_label>
    <arm_group_label>Group 2 (HFNC followed by CPAP)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Transcutaneous carbon dioxide</intervention_name>
    <description>Babies will have transcutaneous carbon dioxide measured during CPAP and HFNC respiratory support.</description>
    <arm_group_label>Group 1 ( CPAP followed by HFNC)</arm_group_label>
    <arm_group_label>Group 2 (HFNC followed by CPAP)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Pharyngeal gas concentrations</intervention_name>
    <description>Measurement of pharyngeal oxygen and carbon dioxide concentration will be done during CPAP and HFNC respiratory support.</description>
    <arm_group_label>Group 1 ( CPAP followed by HFNC)</arm_group_label>
    <arm_group_label>Group 2 (HFNC followed by CPAP)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Tidal volume</intervention_name>
    <description>Tidal breathing indices including tidal volume and FRC base line changes will be recorded during CPAP and HFNC respiratory support.</description>
    <arm_group_label>Group 1 ( CPAP followed by HFNC)</arm_group_label>
    <arm_group_label>Group 2 (HFNC followed by CPAP)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  They are less than 37 weeks' gestation at birth and more than 5 days of age&#xD;
&#xD;
          -  Are on non-invasive respiratory support and&#xD;
&#xD;
          -  The parent(s) have given written informed consent to their baby's participation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Infants who are clinically unstable and unsuitable for non-invasive respiratory&#xD;
             support as judged by attending neonatology consultant clinician.&#xD;
&#xD;
          -  Participation in a concurrent study that prohibits inclusion in other trials&#xD;
&#xD;
          -  Known major upper airway, lower respiratory tract, cardiac or gastrointestinal tract&#xD;
             anomaly&#xD;
&#xD;
          -  Current complications such as pneumothorax.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>5 Days</minimum_age>
    <maximum_age>4 Months</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christopher O'Brien, MRCP, FRCPCH</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Newcastle upon Tyne Hospitals NHS Foundation NHS Trust</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Christopher O'Brien, MRCP, FRCPCH</last_name>
    <phone>0044-191-2825089</phone>
    <email>christopher.o'brien@nuth.nhs.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Saikiran Gopalakaje, MD, MRCPCH</last_name>
    <phone>0044-191-2821614</phone>
    <email>saikiran.gopalakaje@nuth.nhs.uk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>The Newcastle upon Tyne Hospitals NHS Foundation Trust</name>
      <address>
        <city>Newcastle upon Tyne</city>
        <state>Tyne and Wear</state>
        <zip>NE1 4LP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>July 24, 2014</study_first_submitted>
  <study_first_submitted_qc>July 24, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 25, 2014</study_first_posted>
  <last_update_submitted>July 24, 2014</last_update_submitted>
  <last_update_submitted_qc>July 24, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 25, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>High flow nasal cannula</keyword>
  <keyword>Continuous Positive Airway Pressure</keyword>
  <keyword>Respiratory physiology</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Distress Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
  </condition_browse>
  <pending_results>
    <submitted>April 20, 2018</submitted>
    <returned>November 21, 2018</returned>
    <submitted>October 1, 2019</submitted>
    <returned>October 24, 2019</returned>
  </pending_results>
  <!-- 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/NCT02200900
org study id: 7022
nct id: NCT02200900
lead sponsor: 
has dmc: Yes
The most commonly used noninvasive respiratory support in preterm babies is Continuous
      Positive Airway Pressure (CPAP), which provides extra breathing support to babies who are
      breathing by themselves). Increasingly High flow Nasal Cannula (HFNC, newer form of extra
      breathing support) therapy has found its way in clinical practice despite lack of good
      physiological data. There are also concerns about its potential to generate higher pressures
      in airways which can cause over distension of lungs.

      We would like to find out the effects of HFNC on

        -  1. Airway pressures in various flow rates and in comparison to CPAP.

        -  2. Breathing markers including respiratory rate (speed of breathing), oxygen and carbon
           dioxide levels, tidal volumes (how much air breathed in with each breath) and airway
           wash out (wash out of waste gas from the airway).

      We plan to study 15 babies each in three different weight categories supported with either
      CPAP or HFNC. The airway pressures, oxygen and carbon dioxide concentration in airway are
      measured by a small plastic catheter (similar to feeding tube but much shorter in length),
      carbon dioxide levels by skin sensors, how fast and how much babies breathe by a special vest
      applied like a layer of clothing. These will be recorded both on HFNC and CPAP. There are no
      blood tests or invasive procedures involved. The baby will be monitored throughout the study
      period of approximately two hours by experienced registrar who is trained to use the study
      device.

      This study will improve our understanding of physiological effects of HFNC and lead to better
      care of preterm babies.
Purpose and design

      Design: Prospective randomised crossover study.

      Purpose:

        -  Raising airway pressure is one of the most important interventions at the disposal of
           clinicians treating patients with respiratory failure. In premature infants Continuous
           Positive Airway Pressure (CPAP) and High Flow Nasal Cannula (HFNC) are noninvasive
           techniques to raise mean airway pressure when intubation is not required. It is not
           clear how clinicians choose between these techniques and there is little data comparing
           the physiological effect of these treatments.

        -  A composite physiological assessment of babies on HFNC and CPAP treatment is required to
           understand how HFNC works. It is important to answer this question to understand how
           best to use HFNC in babies.

        -  This proposal is designed to provide information on physiological effects of both
           therapies in same population of babies across different weight categories. The study
           protocol involves use of same HFNC device that is currently being used in neonatal unit.

      Interventions:

      1. A small plastic catheter tip transducer (Gaeltec) will be placed in upper breathing
      passage (nasopharynx or oropharynx) using standard methods. From this we will measure airway
      pressures and respiratory gas concentrations.

      The catheter will be removed soon after the study is completed. This procedure will be done
      once during the study.

      2. Breathing markers (Tidal breathing indices) will be measured by non invasive method using
      Volusense method where a vest will be applied over the chest and abdomen like a layer of
      clothing. The Volusense vest will be removed soon after the procedure. This process is done
      once during the study.

      3. Blood carbon dioxide (CO2) levels will be measured by a non invasive transcutaneous sensor
      applied to the skin (Tosca Radiometer). This skin sensor will be removed soon after the study
      is completed.

        1. The baby must be clinically stable for preceding 12 hours on noninvasive breathing
           support (not meeting exit criteria). The babies will be randomised to either group 1
           (CPAP first followed by HFNC) or group 2 (HFNC first followed by CPAP) by computerised
           software programme.

        2. The measuring devices namely nasopharyngeal catheter, Volusense vest and transcutaneous
           CO2 sensor are placed as per standard methods.

        3. After ensuring babies' clinical stability the measurements are recorded at HFNC gas flow
           rate range from 2 litres to 8 litres per minute and in CPAP of 6 cm of water pressure
           level.

        4. The study lasts about 2 hours. The baby spends 10 minutes at each HFNC flow rate level
           and 30 minutes of equilibration period when support will be changed between HFNC and
           CPAP.

        5. Routine measurement of heart rate, respiratory rate and oxygen saturations will be done
           as per standard neonatal practice. The above data will be recorded electronically for
           analysis with total study duration around 120 minutes.

        6. Respiratory support can be terminated at any point if clinically not indicated.

      The researcher is an experienced neonatal registrar who will be directly observing the baby
      throughout the study.

      Measurements would be discontinued if any pre set exit criteria is noted.

      Statistics: A total of 45 babies (15 babies in each weight category: <1000 grams, 1001500
      grams and >1500 grams) will be studied.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Nasopharyngeal pressures (pressures in upper breathing passages) generated by HFNC at flow rate range of 2 to 8 L/min.
time frame: Primary outcome recorded during the measurement period of 2 hours.
description: The range of pressures generated during high flow nasal cannula treatment over flow rate range of 2 to 8 litres per minute will be recorded during the study period.
measure: Nasopharyngeal pressures (pressures in upper breathing passages) generated at CPAP of 6 cm of water
time frame: Pressures recorded during the study period of 2 hours
description: The nasopharyngeal pressures recorded during CPAP of 6 cm of water pressure will be documented.
measure: The effect of changing flow rate of HFNC on following physiological parameters Oxygen saturation and transcutaneous CO2, Respiratory rate, Tidal volume and FRC baseline change.
time frame: Recorded during the study period of 2 hours
description: The physiological parameters including oxygen saturation and transcutaneous CO2, Respiratory rate, Tidal volume and Functional Residual Capacity (FRC) baseline change will be recorded by monitors during the study period.
measure: The relationship of flow and inspired oxygen concentration on actual laryngeal inspired and expired O2 and CO2 concentration in HFNC and CPAP.
time frame: Recorded during the 2 hour study period
description: The relationship of flow and inspired oxygen concentration on actual pharyngeal inspired and expired O2 and CO2 concentration in HFNC and CPAP will be noted by gas analyser.
arm group label: Group 1 ( CPAP followed by HFNC)
arm group type: Active Comparator
description: In this group pharyngeal pressure, transcutaneous carbon dioxide concentration, tidal volumes and pharyngeal gas concentrations will be recorded on CPAP first followed by HFNC.
arm group label: Group 2 (HFNC followed by CPAP)
arm group type: Active Comparator
description: In this group pharyngeal pressure, transcutaneous carbon dioxide concentration, tidal volumes and pharyngeal gas concentrations will be recorded on HFNC first followed by CPAP.
intervention type: Other
intervention name: Pharyngeal pressure
description: Babies will have pharyngeal pressures measured during the CPAP and HFNC respiratory support.
arm group label: Group 1 ( CPAP followed by HFNC)
arm group label: Group 2 (HFNC followed by CPAP)
intervention type: Other
intervention name: Transcutaneous carbon dioxide
description: Babies will have transcutaneous carbon dioxide measured during CPAP and HFNC respiratory support.
arm group label: Group 1 ( CPAP followed by HFNC)
arm group label: Group 2 (HFNC followed by CPAP)
intervention type: Other
intervention name: Pharyngeal gas concentrations
description: Measurement of pharyngeal oxygen and carbon dioxide concentration will be done during CPAP and HFNC respiratory support.
arm group label: Group 1 ( CPAP followed by HFNC)
arm group label: Group 2 (HFNC followed by CPAP)
intervention type: Other
intervention name: Tidal volume
description: Tidal breathing indices including tidal volume and FRC base line changes will be recorded during CPAP and HFNC respiratory support.
arm group label: Group 1 ( CPAP followed by HFNC)
arm group label: Group 2 (HFNC followed by CPAP)
criteria: 
gender: All
minimum age: 5 Days
maximum age: 4 Months
healthy volunteers: No
last name: Christopher O'Brien, MRCP, FRCPCH
role: Principal Investigator
affiliation: The Newcastle upon Tyne Hospitals NHS Foundation NHS Trust
last name: Christopher O'Brien, MRCP, FRCPCH
phone: 0044-191-2825089
email: christopher.o'brien@nuth.nhs.uk
last name: Saikiran Gopalakaje, MD, MRCPCH
phone: 0044-191-2821614
email: saikiran.gopalakaje@nuth.nhs.uk
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
submitted: April 20, 2018
returned: November 21, 2018
submitted: October 1, 2019
returned: October 24, 2019