<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/NCT04500353</url>
  </required_header>
  <id_info>
    <org_study_id>ROSA.01</org_study_id>
    <nct_id>NCT04500353</nct_id>
  </id_info>
  <brief_title>Routine Or Selective Application of a Face Mask for Preterm Infants at Birth: the ROSA Trial</brief_title>
  <acronym>ROSA</acronym>
  <official_title>A Randomised Trial of Routine or Selective Application of a Face Mask for Preterm Infants at Birth</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University College Dublin</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University College Dublin</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>
      International guidelines recommend giving positive pressure ventilation (PPV) by face mask to&#xD;
      newborns who do not breathe or have a slow heart rate at birth. Preterm infants are at high&#xD;
      risk of developing respiratory distress syndrome (RDS) and many are treated with continuous&#xD;
      positive airway pressure (CPAP) in the neonatal intensive care unit (NICU). Though the&#xD;
      majority of preterm infants breathe spontaneously at birth, many clinicians routinely apply a&#xD;
      face mask to preterm infants shortly after birth in the delivery room (DR) to give them CPAP.&#xD;
      However, applying a face mask may inhibit spontaneous breathing in newborns. In this study,&#xD;
      premature babies will be randomly assigned to have a face mask routinely applied for CPAP&#xD;
      shortly after birth; or to have a face mask selectively applied only for PPV if they are not&#xD;
      breathing or have a slow heart beat in the first 5 minutes of life, or for CPAP if they have&#xD;
      signs of respiratory distress after 5 minutes. The investigators will determine whether fewer&#xD;
      participants who have the mask selectively applied receive PPV in the DR.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Newly born babies have fluid-filled lungs that they must quickly aerate after birth. Compared&#xD;
      to infants born at term, preterm babies have greater difficulty in establishing and&#xD;
      maintaining aeration of their lungs; this leaves them at increased risk of developing&#xD;
      respiratory distress syndrome (RDS). Infants who develop RDS are treated with nasal&#xD;
      continuous positive airway pressure (CPAP), and may progress to treatment with surfactant and&#xD;
      mechanical ventilation, in the Neonatal Intensive Care Unit (NICU).&#xD;
&#xD;
      The Neonatal Task Force of the International Liaison Committee on Resuscitation (ILCOR) makes&#xD;
      recommendations on the treatment of infants at birth. ILCOR recommends assessing the&#xD;
      breathing and heart rate (HR) of all newborns, and:&#xD;
&#xD;
        1. Giving positive pressure ventilation (PPV) to babies who have a HR &lt; 100bpm, gasping or&#xD;
           apnoea&#xD;
&#xD;
        2. Considering giving CPAP to babies who have laboured breathing or persistent cyanosis&#xD;
&#xD;
      Most preterm infants breathe spontaneously at birth. Despite this, the majority of preterm&#xD;
      infants have a facemask applied for respiratory support immediately after birth, usually&#xD;
      before the HR has been determined. Clinicians presumably do this to give early support to&#xD;
      infants they believe are at high risk of developing RDS in an attempt to prevent or lessen&#xD;
      the severity of the disease.&#xD;
&#xD;
      There is little evidence that giving preterm infants prophylactic nasal CPAP may be superior&#xD;
      to supportive care with oxygen. A study that compared nasopharyngeal CPAP to supportive care&#xD;
      with oxygen performed before antenatal steroids were routinely given found no difference in&#xD;
      the rate of development of RDS with the application of CPAP. Two more recent studies did not&#xD;
      show that early application of nasal CPAP reduced the rate of intubation or treatment with&#xD;
      surfactant. In these studies CPAP was given by nasal prongs and was started at 15 - 30&#xD;
      minutes of life, not immediately with a facemask. There is no evidence that facemask CPAP&#xD;
      immediately after birth prevents or reduces the severity of RDS.&#xD;
&#xD;
      Application of a face mask has been demonstrated to inhibit spontaneous breathing in many&#xD;
      term infants. Cold gas flow, such as that provided by a T-piece, can inhibit spontaneous&#xD;
      breathing in term infants. Application of a face mask for breathing support appears to&#xD;
      inhibit breathing in a greater proportion of preterm infants. Considerable force is applied&#xD;
      to the head when face mask PPV is given to a mannequin in the supine position.&#xD;
&#xD;
      Routinely applying a face mask for respiratory support may be unnecessary in many premature&#xD;
      babies. It may inhibit their spontaneous breathing and result in them receiving facemask PPV&#xD;
      more frequently in the DR. It may also affect how well they breathe in the first day of life&#xD;
      and increase the rate of treatment with nasal CPAP in the NICU.&#xD;
&#xD;
      METHODS&#xD;
&#xD;
      RANDOMISATION AND GROUP ASSIGNMENT Participants will be randomly assigned to &quot;SELECTIVE&quot; or&#xD;
      &quot;ROUTINE&quot; groups in a 1:1 ratio. The group assignment schedule will be generated in blocks of&#xD;
      4 using a random number table, and will be stratified by gestational age (23 - 27, 28 -&#xD;
      31+6). It will be kept on a concealed from investigators and treating clinicians. Group&#xD;
      assignment will be written on cards and placed in sequentially numbered, sealed, opaque&#xD;
      envelopes. Infants of multiple gestations will be randomised as individuals.&#xD;
&#xD;
      The envelopes will be contained in 2 boxes for GA strata and kept in the NICU. The next&#xD;
      envelope in the sequence will be taken from the appropriate box and brought to the DR, where&#xD;
      it will be opened just before delivery.&#xD;
&#xD;
      MASKING It is not possible to mask caregivers to group assignment.&#xD;
&#xD;
      INTERVENTIONS&#xD;
&#xD;
      ALL INFANTS Infants in both groups will have their umbilical cord clamped at or after 1&#xD;
      minute of age; they will not have a mask applied for respiratory support during this time.&#xD;
      Infants will then be transferred to resuscitaire, placed supine under radiant heat and have a&#xD;
      hat applied. All infants will be placed in polyethylene bag. A pulse oximeter will be placed&#xD;
      on the right wrist.&#xD;
&#xD;
      A T-piece device (Neopuff, Fisher &amp; Paykel Healthcare, Auckland NZ; or Dräger Resuscitaire&#xD;
      (Drager healthcare, Lübeck, Germany) and round face mask (Fisher &amp; Paykel Healthcare,&#xD;
      Auckland NZ) of appropriate size for the baby will be used to give respiratory support to&#xD;
      infants in both groups. The T-piece will have gas flow set at 8 - 10 L/min, with settings&#xD;
      PEEP 6cmH2O, and PIP 25cmH2O. There will be an air/oxygen blender in the circuit and the FiO2&#xD;
      will be initially set at 30%. The FiO2 will not be adjusted before 5 minutes of age.&#xD;
&#xD;
      SELECTIVE GROUP Infants assigned to the &quot;SELECTIVE&quot; group will be placed supine to breathe&#xD;
      spontaneously. If SpO2 &lt; 70% at 5 minutes and their respiratory effort is good, they will be&#xD;
      given give free flow oxygen (i.e. the mask will be placed in front of, but not directly in&#xD;
      contact with, the infant's face). The FiO2 may be increased at 1 minute intervals thereafter,&#xD;
      aiming for SpO2 ≥ 90% at 10 minutes of life.&#xD;
&#xD;
      Infants in the &quot;SELECTIVE&quot; group will have mask PPV if they are apnoeic or have HR &lt; 100bpm&#xD;
      at any time in the DR. Clinicians may consider applying facemask to give CPAP if the infants&#xD;
      breathing is laboured (i.e. there are signs of respiratory distress - grunting,&#xD;
      intercostal/subcostal/sternal recessions) after 5 minutes of age.&#xD;
&#xD;
      ROUTINE GROUP Infants assigned to the &quot;ROUTINE&quot; group will be placed supine on the&#xD;
      resuscitaire and have facemask CPAP applied as soon as possible after they arrive. If SpO2 &lt;&#xD;
      70% at 5 minutes, the FiO2 may be increased at 1 minute intervals, aiming for SpO2 ≥ 90% at&#xD;
      10 minutes of life.&#xD;
&#xD;
      Infants in the &quot;ROUTINE&quot; group will have facemask PPV if they are apnoeic or have HR &lt; 100bpm&#xD;
      at any time in the DR. Mask respiratory support may be withdrawn as and when desired by&#xD;
      clinical staff.&#xD;
&#xD;
      RESUCE TREATMENT All other treatments - i.e. endotracheal intubation for PPV, chest&#xD;
      compressions, adrenaline, volume - w ill be given at the discretion of the treating&#xD;
      clinicians and in accordance with ILCOR recommendations.&#xD;
&#xD;
      SAMPLE SIZE ESTIMATION To show a reduction in the proportion of babies receiving PPV with&#xD;
      routine application from 60% to 40% with selective application with 80% power and α of 0.05,&#xD;
      the investigators need to recruit 200 infants.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 11, 2020</start_date>
  <completion_date type="Anticipated">March 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2022</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>
    <intervention_model_description>Randomised parallel group study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Masking of caregivers not feasible due to the nature of the intervention</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>The proportion of participants who receive face mask PPV in the delivery room DR</measure>
    <time_frame>Within 30 minutes of birth</time_frame>
    <description>The proportion of participants who receive face mask positive pressure ventilation (PPV) in the delivery room (DR)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The proportion of participants who receive face mask CPAP in the first 5 minutes of life</measure>
    <time_frame>5 minutes</time_frame>
    <description>The proportion of participants who receive face mask (continuous positive airway pressure) CPAP in the first 5 minutes of life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of participants who receive face mask PPV in the first 5 minutes of life</measure>
    <time_frame>5 minutes</time_frame>
    <description>The proportion of participants who receive face mask PPV in the first 5 minutes of life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HR at 5 minutes of life</measure>
    <time_frame>5 minutes</time_frame>
    <description>Heart rate (HR) at 5 minutes of life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SpO2 at 5 minutes of life</measure>
    <time_frame>5 minutes</time_frame>
    <description>Oxygen saturation (SpO2) at 5 minutes of life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of participants who receive face mask CPAP in the DR</measure>
    <time_frame>Within 30 minutes of birth</time_frame>
    <description>The proportion of participants who receive face mask CPAP in the DR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of PPV in the DR</measure>
    <time_frame>Within 30 minutes of birth</time_frame>
    <description>Duration of PPV in the DR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of participants who are intubated in the DR</measure>
    <time_frame>Within 30 minutes of birth</time_frame>
    <description>The proportion of participants who are intubated in the DR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of participants who receive chest compressions in the DR</measure>
    <time_frame>Within 30 minutes of birth</time_frame>
    <description>The proportion of participants who receive chest compressions in the DR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of participants who receive volume in the DR</measure>
    <time_frame>Within 30 minutes of birth</time_frame>
    <description>The proportion of participants who receive volume in the DR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of participants who receive adrenaline in the DR</measure>
    <time_frame>Within 30 minutes of birth</time_frame>
    <description>The proportion of participants who receive adrenaline in the DR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum FiO2 in the DR</measure>
    <time_frame>Within 20 minutes of birth</time_frame>
    <description>Maximum fraction of inspired oxygen (FiO2) in the DR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apgar score at 5 minutes</measure>
    <time_frame>5 minutes</time_frame>
    <description>Apgar score at 5 minutes (scale 0 -10, higher scores indicate better outcome)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apgar score at 10 minutes</measure>
    <time_frame>10 minutes</time_frame>
    <description>Apgar score at 10 minutes (scale 0 -10, higher scores indicate better outcome)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Respiratory support in transport to NICU</measure>
    <time_frame>Within 45 minutes of birth</time_frame>
    <description>Respiratory support in transport to the neonatal intensive care unit (NICU)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of participants who receive NCPAP in NICU</measure>
    <time_frame>Within one month</time_frame>
    <description>The proportion of participants who receive nasal CPAP in NICU</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of participants who receive endotracheal ventilation in NICU</measure>
    <time_frame>Within one month</time_frame>
    <description>The proportion of participants who receive endotracheal ventilation in NICU</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of participants who receive surfactant treatment</measure>
    <time_frame>Within one month</time_frame>
    <description>The proportion of participants who receive surfactant treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of participants who have a pneumothorax drained</measure>
    <time_frame>Within one month</time_frame>
    <description>The proportion of participants who have a pneumothorax drained</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of participants who survive free of BPD</measure>
    <time_frame>Day 28 of life</time_frame>
    <description>The proportion of participants who are alive and not receiving respiratory support or supplemental oxygen on day 28 of life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of participants who receive survive free of CLD</measure>
    <time_frame>36 weeks corrected</time_frame>
    <description>The proportion of participants who are alive and not receiving respiratory support or supplemental oxygen at 36 weeks corrected age</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of participants who receive postnatal steroids</measure>
    <time_frame>Through study completion, an average of 2-3 months in survivors</time_frame>
    <description>The proportion of participants who receive postnatal steroids</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of participants who receive home oxygen therapy</measure>
    <time_frame>Through study completion, an average of 2-3 months in survivors</time_frame>
    <description>The proportion of participants who receive home oxygen therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of participants who die before hospital discharge</measure>
    <time_frame>Through study completion, an average of 2-3 months in survivors</time_frame>
    <description>The proportion of participants who die before hospital discharge</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Infant, Premature, Diseases</condition>
  <condition>Continuous Positive Airway Pressure</condition>
  <condition>Positive-Pressure Respiration</condition>
  <condition>Resuscitation</condition>
  <condition>Respiratory Distress Syndrome, Newborn</condition>
  <arm_group>
    <arm_group_label>Routine face mask application</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Routine application of a face mask shortly after birth to deliver continuous positive airway pressure (CPAP)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Selective face mask application</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Selective application of a face mask to give positive pressure ventilation (PPV) for apnoea or bradycardia [heart rate (HR) &lt; 100 beats per minute (bpm)] at any time in the delivery room (DR); or to give CPAP for signs of respiratory distress after 5 minutes of life</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Face mask application for CPAP and/or PPV delivery</intervention_name>
    <description>Face mask application for CPAP and/or PPV delivery</description>
    <arm_group_label>Routine face mask application</arm_group_label>
    <arm_group_label>Selective face mask application</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Born before 32 weeks gestational age by best obstetric estimate&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Infants with major congenital anomalies&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>0 Minutes</minimum_age>
    <maximum_age>5 Minutes</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Colm PF O'Donnell, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Maternity Hospital; University College Dublin</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Colm PF O'Donnell, PhD</last_name>
    <phone>35316373100</phone>
    <phone_ext>3186</phone_ext>
    <email>codonnell@nmh.ie</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Lisa K McCarthy, PhD</last_name>
    <phone>35316373100</phone>
    <email>lmccarthy@nmh.ie</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>National Maternity Hospital</name>
      <address>
        <city>Dublin</city>
        <zip>D02 YH21</zip>
        <country>Ireland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Colm PF O'Donnell, PhD</last_name>
      <phone>35316373100</phone>
      <phone_ext>3186</phone_ext>
      <email>codonnell@nmh.ie</email>
    </contact>
    <contact_backup>
      <last_name>Lisa K McCarthy, PhD</last_name>
      <phone>35316373100</phone>
      <email>lmccarthy@nmh.ie</email>
    </contact_backup>
    <investigator>
      <last_name>Eoin M O Currain, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Ireland</country>
  </location_countries>
  <reference>
    <citation>Perlman JM, Wyllie J, Kattwinkel J, Wyckoff MH, Aziz K, Guinsburg R, Kim HS, Liley HG, Mildenhall L, Simon WM, Szyld E, Tamura M, Velaphi S; Neonatal Resuscitation Chapter Collaborators. Part 7: Neonatal Resuscitation: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Circulation. 2015 Oct 20;132(16 Suppl 1):S204-41. doi: 10.1161/CIR.0000000000000276. No abstract available.</citation>
    <PMID>26472855</PMID>
  </reference>
  <reference>
    <citation>O'Donnell CP, Kamlin CO, Davis PG, Morley CJ. Crying and breathing by extremely preterm infants immediately after birth. J Pediatr. 2010 May;156(5):846-7. doi: 10.1016/j.jpeds.2010.01.007. Epub 2010 Mar 16.</citation>
    <PMID>20236659</PMID>
  </reference>
  <reference>
    <citation>Murphy MC, McCarthy LK, O'Donnell CPF. Crying and breathing by new-born preterm infants after early or delayed cord clamping. Arch Dis Child Fetal Neonatal Ed. 2020 May;105(3):331-333. doi: 10.1136/archdischild-2018-316592. Epub 2019 May 13.</citation>
    <PMID>31085675</PMID>
  </reference>
  <reference>
    <citation>Katheria A, Arnell K, Brown M, Hassen K, Maldonado M, Rich W, Finer N. A pilot randomized controlled trial of EKG for neonatal resuscitation. PLoS One. 2017 Nov 3;12(11):e0187730. doi: 10.1371/journal.pone.0187730. eCollection 2017.</citation>
    <PMID>29099872</PMID>
  </reference>
  <reference>
    <citation>Kuypers KLAM, Lamberska T, Martherus T, Dekker J, Bohringer S, Hooper SB, Plavka R, Te Pas AB. The effect of a face mask for respiratory support on breathing in preterm infants at birth. Resuscitation. 2019 Nov;144:178-184. doi: 10.1016/j.resuscitation.2019.08.043. Epub 2019 Sep 12.</citation>
    <PMID>31521774</PMID>
  </reference>
  <reference>
    <citation>Murphy MC, McCarthy LK, O'Donnell CPF. Initiation of respiratory support for extremely preterm infants at birth. Arch Dis Child Fetal Neonatal Ed. 2021 Mar;106(2):208-210. doi: 10.1136/archdischild-2020-319798. Epub 2020 Aug 26.</citation>
    <PMID>32847832</PMID>
  </reference>
  <reference>
    <citation>Subramaniam P, Ho JJ, Davis PG. Prophylactic nasal continuous positive airway pressure for preventing morbidity and mortality in very preterm infants. Cochrane Database Syst Rev. 2016 Jun 14;(6):CD001243. doi: 10.1002/14651858.CD001243.pub3.</citation>
    <PMID>27315509</PMID>
  </reference>
  <reference>
    <citation>Sandri F, Ancora G, Lanzoni A, Tagliabue P, Colnaghi M, Ventura ML, Rinaldi M, Mondello I, Gancia P, Salvioli GP, Orzalesi M, Mosca F. Prophylactic nasal continuous positive airways pressure in newborns of 28-31 weeks gestation: multicentre randomised controlled clinical trial. Arch Dis Child Fetal Neonatal Ed. 2004 Sep;89(5):F394-8. doi: 10.1136/adc.2003.037010.</citation>
    <PMID>15321956</PMID>
  </reference>
  <reference>
    <citation>Goncalves-Ferri WA, Martinez FE, Caldas JP, Marba ST, Fekete S, Rugolo L, Tanuri C, Leone C, Sancho GA, Almeida MF, Guinsburg R. Application of continuous positive airway pressure in the delivery room: a multicenter randomized clinical trial. Braz J Med Biol Res. 2014 Feb;47(3):259-64. doi: 10.1590/1414-431X20133278. Epub 2014 Jan 29.</citation>
    <PMID>24554040</PMID>
  </reference>
  <reference>
    <citation>Chernick V, Avery ME. Response of premature infants with periodic breathing to ventilatory stimuli. J Appl Physiol. 1966 Mar;21(2):434-40. doi: 10.1152/jappl.1966.21.2.434. No abstract available.</citation>
    <PMID>5949048</PMID>
  </reference>
  <reference>
    <citation>Dolfin T, Duffty P, Wilkes D, England S, Bryan H. Effects of a face mask and pneumotachograph on breathing in sleeping infants. Am Rev Respir Dis. 1983 Dec;128(6):977-9. doi: 10.1164/arrd.1983.128.6.977.</citation>
    <PMID>6650989</PMID>
  </reference>
  <reference>
    <citation>Fleming PJ, Levine MR, Goncalves A. Changes in respiratory pattern resulting from the use of a facemask to record respiration in newborn infants. Pediatr Res. 1982 Dec;16(12):1031-4. doi: 10.1203/00006450-198212000-00013.</citation>
    <PMID>7155672</PMID>
  </reference>
  <reference>
    <citation>Ramet J, Praud JP, D'Allest AM, Dehan M, Gaultier C. Trigeminal airstream stimulation. Maturation-related cardiac and respiratory responses during REM sleep in human infants. Chest. 1990 Jul;98(1):92-6. doi: 10.1378/chest.98.1.92.</citation>
    <PMID>2361419</PMID>
  </reference>
  <reference>
    <citation>van Vonderen JJ, Kleijn TA, Schilleman K, Walther FJ, Hooper SB, te Pas AB. Compressive force applied to a manikin's head during mask ventilation. Arch Dis Child Fetal Neonatal Ed. 2012 Jul;97(4):F254-8. doi: 10.1136/archdischild-2011-300336. Epub 2011 Dec 5.</citation>
    <PMID>22147285</PMID>
  </reference>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>July 24, 2020</study_first_submitted>
  <study_first_submitted_qc>August 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 5, 2020</study_first_posted>
  <last_update_submitted>May 17, 2022</last_update_submitted>
  <last_update_submitted_qc>May 17, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 18, 2022</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>Respiratory Distress Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
    <mesh_term>Infant, Premature, Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Anonymised data will be shared for studies approved by the chief and principal investigators</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Data will be available after the primary report of the study has been published and will be available for 5 years</ipd_time_frame>
    <ipd_access_criteria>Requests for data that are accompanied by a protocol that describes the nature and purpose of the study, the data that is required and how it will be analysed will be considered by the chief and principal investigators. Studies that are determined not to be contrary to partcipants' interests; and to be consistent with the purpose for which consent was given for the original study and methodologically sound may be approved</ipd_access_criteria>
  </patient_data>
  <!-- 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/NCT04500353
org study id: ROSA.01
nct id: NCT04500353
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
International guidelines recommend giving positive pressure ventilation (PPV) by face mask to
      newborns who do not breathe or have a slow heart rate at birth. Preterm infants are at high
      risk of developing respiratory distress syndrome (RDS) and many are treated with continuous
      positive airway pressure (CPAP) in the neonatal intensive care unit (NICU). Though the
      majority of preterm infants breathe spontaneously at birth, many clinicians routinely apply a
      face mask to preterm infants shortly after birth in the delivery room (DR) to give them CPAP.
      However, applying a face mask may inhibit spontaneous breathing in newborns. In this study,
      premature babies will be randomly assigned to have a face mask routinely applied for CPAP
      shortly after birth; or to have a face mask selectively applied only for PPV if they are not
      breathing or have a slow heart beat in the first 5 minutes of life, or for CPAP if they have
      signs of respiratory distress after 5 minutes. The investigators will determine whether fewer
      participants who have the mask selectively applied receive PPV in the DR.
Newly born babies have fluid-filled lungs that they must quickly aerate after birth. Compared
      to infants born at term, preterm babies have greater difficulty in establishing and
      maintaining aeration of their lungs; this leaves them at increased risk of developing
      respiratory distress syndrome (RDS). Infants who develop RDS are treated with nasal
      continuous positive airway pressure (CPAP), and may progress to treatment with surfactant and
      mechanical ventilation, in the Neonatal Intensive Care Unit (NICU).

      The Neonatal Task Force of the International Liaison Committee on Resuscitation (ILCOR) makes
      recommendations on the treatment of infants at birth. ILCOR recommends assessing the
      breathing and heart rate (HR) of all newborns, and:

        1. Giving positive pressure ventilation (PPV) to babies who have a HR < 100bpm, gasping or
           apnoea

        2. Considering giving CPAP to babies who have laboured breathing or persistent cyanosis

      Most preterm infants breathe spontaneously at birth. Despite this, the majority of preterm
      infants have a facemask applied for respiratory support immediately after birth, usually
      before the HR has been determined. Clinicians presumably do this to give early support to
      infants they believe are at high risk of developing RDS in an attempt to prevent or lessen
      the severity of the disease.

      There is little evidence that giving preterm infants prophylactic nasal CPAP may be superior
      to supportive care with oxygen. A study that compared nasopharyngeal CPAP to supportive care
      with oxygen performed before antenatal steroids were routinely given found no difference in
      the rate of development of RDS with the application of CPAP. Two more recent studies did not
      show that early application of nasal CPAP reduced the rate of intubation or treatment with
      surfactant. In these studies CPAP was given by nasal prongs and was started at 15 - 30
      minutes of life, not immediately with a facemask. There is no evidence that facemask CPAP
      immediately after birth prevents or reduces the severity of RDS.

      Application of a face mask has been demonstrated to inhibit spontaneous breathing in many
      term infants. Cold gas flow, such as that provided by a T-piece, can inhibit spontaneous
      breathing in term infants. Application of a face mask for breathing support appears to
      inhibit breathing in a greater proportion of preterm infants. Considerable force is applied
      to the head when face mask PPV is given to a mannequin in the supine position.

      Routinely applying a face mask for respiratory support may be unnecessary in many premature
      babies. It may inhibit their spontaneous breathing and result in them receiving facemask PPV
      more frequently in the DR. It may also affect how well they breathe in the first day of life
      and increase the rate of treatment with nasal CPAP in the NICU.

      METHODS

      RANDOMISATION AND GROUP ASSIGNMENT Participants will be randomly assigned to "SELECTIVE" or
      "ROUTINE" groups in a 1:1 ratio. The group assignment schedule will be generated in blocks of
      4 using a random number table, and will be stratified by gestational age (23 - 27, 28 -
      31+6). It will be kept on a concealed from investigators and treating clinicians. Group
      assignment will be written on cards and placed in sequentially numbered, sealed, opaque
      envelopes. Infants of multiple gestations will be randomised as individuals.

      The envelopes will be contained in 2 boxes for GA strata and kept in the NICU. The next
      envelope in the sequence will be taken from the appropriate box and brought to the DR, where
      it will be opened just before delivery.

      MASKING It is not possible to mask caregivers to group assignment.

      INTERVENTIONS

      ALL INFANTS Infants in both groups will have their umbilical cord clamped at or after 1
      minute of age; they will not have a mask applied for respiratory support during this time.
      Infants will then be transferred to resuscitaire, placed supine under radiant heat and have a
      hat applied. All infants will be placed in polyethylene bag. A pulse oximeter will be placed
      on the right wrist.

      A T-piece device (Neopuff, Fisher & Paykel Healthcare, Auckland NZ; or Dräger Resuscitaire
      (Drager healthcare, Lübeck, Germany) and round face mask (Fisher & Paykel Healthcare,
      Auckland NZ) of appropriate size for the baby will be used to give respiratory support to
      infants in both groups. The T-piece will have gas flow set at 8 - 10 L/min, with settings
      PEEP 6cmH2O, and PIP 25cmH2O. There will be an air/oxygen blender in the circuit and the FiO2
      will be initially set at 30%. The FiO2 will not be adjusted before 5 minutes of age.

      SELECTIVE GROUP Infants assigned to the "SELECTIVE" group will be placed supine to breathe
      spontaneously. If SpO2 < 70% at 5 minutes and their respiratory effort is good, they will be
      given give free flow oxygen (i.e. the mask will be placed in front of, but not directly in
      contact with, the infant's face). The FiO2 may be increased at 1 minute intervals thereafter,
      aiming for SpO2 ≥ 90% at 10 minutes of life.

      Infants in the "SELECTIVE" group will have mask PPV if they are apnoeic or have HR < 100bpm
      at any time in the DR. Clinicians may consider applying facemask to give CPAP if the infants
      breathing is laboured (i.e. there are signs of respiratory distress - grunting,
      intercostal/subcostal/sternal recessions) after 5 minutes of age.

      ROUTINE GROUP Infants assigned to the "ROUTINE" group will be placed supine on the
      resuscitaire and have facemask CPAP applied as soon as possible after they arrive. If SpO2 <
      70% at 5 minutes, the FiO2 may be increased at 1 minute intervals, aiming for SpO2 ≥ 90% at
      10 minutes of life.

      Infants in the "ROUTINE" group will have facemask PPV if they are apnoeic or have HR < 100bpm
      at any time in the DR. Mask respiratory support may be withdrawn as and when desired by
      clinical staff.

      RESUCE TREATMENT All other treatments - i.e. endotracheal intubation for PPV, chest
      compressions, adrenaline, volume - w ill be given at the discretion of the treating
      clinicians and in accordance with ILCOR recommendations.

      SAMPLE SIZE ESTIMATION To show a reduction in the proportion of babies receiving PPV with
      routine application from 60% to 40% with selective application with 80% power and α of 0.05,
      the investigators need to recruit 200 infants.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomised parallel group study
primary purpose: Treatment
masking: None (Open Label)
masking description: Masking of caregivers not feasible due to the nature of the intervention
measure: The proportion of participants who receive face mask PPV in the delivery room DR
time frame: Within 30 minutes of birth
description: The proportion of participants who receive face mask positive pressure ventilation (PPV) in the delivery room (DR)
measure: The proportion of participants who receive face mask CPAP in the first 5 minutes of life
time frame: 5 minutes
description: The proportion of participants who receive face mask (continuous positive airway pressure) CPAP in the first 5 minutes of life
measure: The proportion of participants who receive face mask PPV in the first 5 minutes of life
time frame: 5 minutes
description: The proportion of participants who receive face mask PPV in the first 5 minutes of life
measure: HR at 5 minutes of life
time frame: 5 minutes
description: Heart rate (HR) at 5 minutes of life
measure: SpO2 at 5 minutes of life
time frame: 5 minutes
description: Oxygen saturation (SpO2) at 5 minutes of life
measure: The proportion of participants who receive face mask CPAP in the DR
time frame: Within 30 minutes of birth
description: The proportion of participants who receive face mask CPAP in the DR
measure: Duration of PPV in the DR
time frame: Within 30 minutes of birth
description: Duration of PPV in the DR
measure: The proportion of participants who are intubated in the DR
time frame: Within 30 minutes of birth
description: The proportion of participants who are intubated in the DR
measure: The proportion of participants who receive chest compressions in the DR
time frame: Within 30 minutes of birth
description: The proportion of participants who receive chest compressions in the DR
measure: The proportion of participants who receive volume in the DR
time frame: Within 30 minutes of birth
description: The proportion of participants who receive volume in the DR
measure: The proportion of participants who receive adrenaline in the DR
time frame: Within 30 minutes of birth
description: The proportion of participants who receive adrenaline in the DR
measure: Maximum FiO2 in the DR
time frame: Within 20 minutes of birth
description: Maximum fraction of inspired oxygen (FiO2) in the DR
measure: Apgar score at 5 minutes
time frame: 5 minutes
description: Apgar score at 5 minutes (scale 0 -10, higher scores indicate better outcome)
measure: Apgar score at 10 minutes
time frame: 10 minutes
description: Apgar score at 10 minutes (scale 0 -10, higher scores indicate better outcome)
measure: Respiratory support in transport to NICU
time frame: Within 45 minutes of birth
description: Respiratory support in transport to the neonatal intensive care unit (NICU)
measure: The proportion of participants who receive NCPAP in NICU
time frame: Within one month
description: The proportion of participants who receive nasal CPAP in NICU
measure: The proportion of participants who receive endotracheal ventilation in NICU
time frame: Within one month
description: The proportion of participants who receive endotracheal ventilation in NICU
measure: The proportion of participants who receive surfactant treatment
time frame: Within one month
description: The proportion of participants who receive surfactant treatment
measure: The proportion of participants who have a pneumothorax drained
time frame: Within one month
description: The proportion of participants who have a pneumothorax drained
measure: The proportion of participants who survive free of BPD
time frame: Day 28 of life
description: The proportion of participants who are alive and not receiving respiratory support or supplemental oxygen on day 28 of life
measure: The proportion of participants who receive survive free of CLD
time frame: 36 weeks corrected
description: The proportion of participants who are alive and not receiving respiratory support or supplemental oxygen at 36 weeks corrected age
measure: The proportion of participants who receive postnatal steroids
time frame: Through study completion, an average of 2-3 months in survivors
description: The proportion of participants who receive postnatal steroids
measure: The proportion of participants who receive home oxygen therapy
time frame: Through study completion, an average of 2-3 months in survivors
description: The proportion of participants who receive home oxygen therapy
measure: The proportion of participants who die before hospital discharge
time frame: Through study completion, an average of 2-3 months in survivors
description: The proportion of participants who die before hospital discharge
arm group label: Routine face mask application
arm group type: Active Comparator
description: Routine application of a face mask shortly after birth to deliver continuous positive airway pressure (CPAP)
arm group label: Selective face mask application
arm group type: Experimental
description: Selective application of a face mask to give positive pressure ventilation (PPV) for apnoea or bradycardia [heart rate (HR) < 100 beats per minute (bpm)] at any time in the delivery room (DR); or to give CPAP for signs of respiratory distress after 5 minutes of life
intervention type: Other
intervention name: Face mask application for CPAP and/or PPV delivery
description: Face mask application for CPAP and/or PPV delivery
arm group label: Routine face mask application
arm group label: Selective face mask application
criteria: 
gender: All
minimum age: 0 Minutes
maximum age: 5 Minutes
healthy volunteers: No
last name: Colm PF O'Donnell, PhD
role: Principal Investigator
affiliation: National Maternity Hospital; University College Dublin
last name: Colm PF O'Donnell, PhD
phone: 35316373100
phone ext: 3186
email: codonnell@nmh.ie
last name: Lisa K McCarthy, PhD
phone: 35316373100
email: lmccarthy@nmh.ie
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: Ireland
citation: Perlman JM, Wyllie J, Kattwinkel J, Wyckoff MH, Aziz K, Guinsburg R, Kim HS, Liley HG, Mildenhall L, Simon WM, Szyld E, Tamura M, Velaphi S; Neonatal Resuscitation Chapter Collaborators. Part 7: Neonatal Resuscitation: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Circulation. 2015 Oct 20;132(16 Suppl 1):S204-41. doi: 10.1161/CIR.0000000000000276. No abstract available.
PMID: 26472855
citation: O'Donnell CP, Kamlin CO, Davis PG, Morley CJ. Crying and breathing by extremely preterm infants immediately after birth. J Pediatr. 2010 May;156(5):846-7. doi: 10.1016/j.jpeds.2010.01.007. Epub 2010 Mar 16.
PMID: 20236659
citation: Murphy MC, McCarthy LK, O'Donnell CPF. Crying and breathing by new-born preterm infants after early or delayed cord clamping. Arch Dis Child Fetal Neonatal Ed. 2020 May;105(3):331-333. doi: 10.1136/archdischild-2018-316592. Epub 2019 May 13.
PMID: 31085675
citation: Katheria A, Arnell K, Brown M, Hassen K, Maldonado M, Rich W, Finer N. A pilot randomized controlled trial of EKG for neonatal resuscitation. PLoS One. 2017 Nov 3;12(11):e0187730. doi: 10.1371/journal.pone.0187730. eCollection 2017.
PMID: 29099872
citation: Kuypers KLAM, Lamberska T, Martherus T, Dekker J, Bohringer S, Hooper SB, Plavka R, Te Pas AB. The effect of a face mask for respiratory support on breathing in preterm infants at birth. Resuscitation. 2019 Nov;144:178-184. doi: 10.1016/j.resuscitation.2019.08.043. Epub 2019 Sep 12.
PMID: 31521774
citation: Murphy MC, McCarthy LK, O'Donnell CPF. Initiation of respiratory support for extremely preterm infants at birth. Arch Dis Child Fetal Neonatal Ed. 2021 Mar;106(2):208-210. doi: 10.1136/archdischild-2020-319798. Epub 2020 Aug 26.
PMID: 32847832
citation: Subramaniam P, Ho JJ, Davis PG. Prophylactic nasal continuous positive airway pressure for preventing morbidity and mortality in very preterm infants. Cochrane Database Syst Rev. 2016 Jun 14;(6):CD001243. doi: 10.1002/14651858.CD001243.pub3.
PMID: 27315509
citation: Sandri F, Ancora G, Lanzoni A, Tagliabue P, Colnaghi M, Ventura ML, Rinaldi M, Mondello I, Gancia P, Salvioli GP, Orzalesi M, Mosca F. Prophylactic nasal continuous positive airways pressure in newborns of 28-31 weeks gestation: multicentre randomised controlled clinical trial. Arch Dis Child Fetal Neonatal Ed. 2004 Sep;89(5):F394-8. doi: 10.1136/adc.2003.037010.
PMID: 15321956
citation: Goncalves-Ferri WA, Martinez FE, Caldas JP, Marba ST, Fekete S, Rugolo L, Tanuri C, Leone C, Sancho GA, Almeida MF, Guinsburg R. Application of continuous positive airway pressure in the delivery room: a multicenter randomized clinical trial. Braz J Med Biol Res. 2014 Feb;47(3):259-64. doi: 10.1590/1414-431X20133278. Epub 2014 Jan 29.
PMID: 24554040
citation: Chernick V, Avery ME. Response of premature infants with periodic breathing to ventilatory stimuli. J Appl Physiol. 1966 Mar;21(2):434-40. doi: 10.1152/jappl.1966.21.2.434. No abstract available.
PMID: 5949048
citation: Dolfin T, Duffty P, Wilkes D, England S, Bryan H. Effects of a face mask and pneumotachograph on breathing in sleeping infants. Am Rev Respir Dis. 1983 Dec;128(6):977-9. doi: 10.1164/arrd.1983.128.6.977.
PMID: 6650989
citation: Fleming PJ, Levine MR, Goncalves A. Changes in respiratory pattern resulting from the use of a facemask to record respiration in newborn infants. Pediatr Res. 1982 Dec;16(12):1031-4. doi: 10.1203/00006450-198212000-00013.
PMID: 7155672
citation: Ramet J, Praud JP, D'Allest AM, Dehan M, Gaultier C. Trigeminal airstream stimulation. Maturation-related cardiac and respiratory responses during REM sleep in human infants. Chest. 1990 Jul;98(1):92-6. doi: 10.1378/chest.98.1.92.
PMID: 2361419
citation: van Vonderen JJ, Kleijn TA, Schilleman K, Walther FJ, Hooper SB, te Pas AB. Compressive force applied to a manikin's head during mask ventilation. Arch Dis Child Fetal Neonatal Ed. 2012 Jul;97(4):F254-8. doi: 10.1136/archdischild-2011-300336. Epub 2011 Dec 5.
PMID: 22147285
responsible party type: Sponsor
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Infant, Premature, Diseases
sharing ipd: Yes
ipd description: Anonymised data will be shared for studies approved by the chief and principal investigators
ipd info type: Study Protocol
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Data will be available after the primary report of the study has been published and will be available for 5 years
ipd access criteria: Requests for data that are accompanied by a protocol that describes the nature and purpose of the study, the data that is required and how it will be analysed will be considered by the chief and principal investigators. Studies that are determined not to be contrary to partcipants' interests; and to be consistent with the purpose for which consent was given for the original study and methodologically sound may be approved