Routine Or Selective Application of a Face Mask for Preterm Infants at Birth: the ROSA Trial (ROSA)
Primary Purpose
Infant, Premature, Diseases, Continuous Positive Airway Pressure, Positive-Pressure Respiration
Status
Recruiting
Phase
Not Applicable
Locations
Ireland
Study Type
Interventional
Intervention
Face mask application for CPAP and/or PPV delivery
Sponsored by
About this trial
This is an interventional treatment trial for Infant, Premature, Diseases
Eligibility Criteria
Inclusion Criteria:
- Born before 32 weeks gestational age by best obstetric estimate
Exclusion Criteria:
- Infants with major congenital anomalies
Sites / Locations
- National Maternity HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Routine face mask application
Selective face mask application
Arm Description
Routine application of a face mask shortly after birth to deliver continuous positive airway pressure (CPAP)
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
Outcomes
Primary Outcome Measures
The proportion of participants who receive face mask PPV in the delivery room DR
The proportion of participants who receive face mask positive pressure ventilation (PPV) in the delivery room (DR)
Secondary Outcome Measures
The proportion of participants who receive face mask CPAP in the first 5 minutes of life
The proportion of participants who receive face mask (continuous positive airway pressure) CPAP in the first 5 minutes of life
The proportion of participants who receive face mask PPV in the first 5 minutes of life
The proportion of participants who receive face mask PPV in the first 5 minutes of life
HR at 5 minutes of life
Heart rate (HR) at 5 minutes of life
SpO2 at 5 minutes of life
Oxygen saturation (SpO2) at 5 minutes of life
The proportion of participants who receive face mask CPAP in the DR
The proportion of participants who receive face mask CPAP in the DR
Duration of PPV in the DR
Duration of PPV in the DR
The proportion of participants who are intubated in the DR
The proportion of participants who are intubated in the DR
The proportion of participants who receive chest compressions in the DR
The proportion of participants who receive chest compressions in the DR
The proportion of participants who receive volume in the DR
The proportion of participants who receive volume in the DR
The proportion of participants who receive adrenaline in the DR
The proportion of participants who receive adrenaline in the DR
Maximum FiO2 in the DR
Maximum fraction of inspired oxygen (FiO2) in the DR
Apgar score at 5 minutes
Apgar score at 5 minutes (scale 0 -10, higher scores indicate better outcome)
Apgar score at 10 minutes
Apgar score at 10 minutes (scale 0 -10, higher scores indicate better outcome)
Respiratory support in transport to NICU
Respiratory support in transport to the neonatal intensive care unit (NICU)
The proportion of participants who receive NCPAP in NICU
The proportion of participants who receive nasal CPAP in NICU
The proportion of participants who receive endotracheal ventilation in NICU
The proportion of participants who receive endotracheal ventilation in NICU
The proportion of participants who receive surfactant treatment
The proportion of participants who receive surfactant treatment
The proportion of participants who have a pneumothorax drained
The proportion of participants who have a pneumothorax drained
The proportion of participants who survive free of BPD
The proportion of participants who are alive and not receiving respiratory support or supplemental oxygen on day 28 of life
The proportion of participants who receive survive free of CLD
The proportion of participants who are alive and not receiving respiratory support or supplemental oxygen at 36 weeks corrected age
The proportion of participants who receive postnatal steroids
The proportion of participants who receive postnatal steroids
The proportion of participants who receive home oxygen therapy
The proportion of participants who receive home oxygen therapy
The proportion of participants who die before hospital discharge
The proportion of participants who die before hospital discharge
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04500353
Brief Title
Routine Or Selective Application of a Face Mask for Preterm Infants at Birth: the ROSA Trial
Acronym
ROSA
Official Title
A Randomised Trial of Routine or Selective Application of a Face Mask for Preterm Infants at Birth
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 11, 2020 (Actual)
Primary Completion Date
December 31, 2022 (Anticipated)
Study Completion Date
March 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University College Dublin
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Detailed Description
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:
Giving positive pressure ventilation (PPV) to babies who have a HR < 100bpm, gasping or apnoea
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infant, Premature, Diseases, Continuous Positive Airway Pressure, Positive-Pressure Respiration, Resuscitation, Respiratory Distress Syndrome, Newborn
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Randomised parallel group study
Masking
None (Open Label)
Masking Description
Masking of caregivers not feasible due to the nature of the intervention
Allocation
Randomized
Enrollment
200 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Routine face mask application
Arm Type
Active Comparator
Arm Description
Routine application of a face mask shortly after birth to deliver continuous positive airway pressure (CPAP)
Arm Title
Selective face mask application
Arm Type
Experimental
Arm 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(s)
Face mask application for CPAP and/or PPV delivery
Intervention Description
Face mask application for CPAP and/or PPV delivery
Primary Outcome Measure Information:
Title
The proportion of participants who receive face mask PPV in the delivery room DR
Description
The proportion of participants who receive face mask positive pressure ventilation (PPV) in the delivery room (DR)
Time Frame
Within 30 minutes of birth
Secondary Outcome Measure Information:
Title
The proportion of participants who receive face mask CPAP in the first 5 minutes of life
Description
The proportion of participants who receive face mask (continuous positive airway pressure) CPAP in the first 5 minutes of life
Time Frame
5 minutes
Title
The proportion of participants who receive face mask PPV in the first 5 minutes of life
Description
The proportion of participants who receive face mask PPV in the first 5 minutes of life
Time Frame
5 minutes
Title
HR at 5 minutes of life
Description
Heart rate (HR) at 5 minutes of life
Time Frame
5 minutes
Title
SpO2 at 5 minutes of life
Description
Oxygen saturation (SpO2) at 5 minutes of life
Time Frame
5 minutes
Title
The proportion of participants who receive face mask CPAP in the DR
Description
The proportion of participants who receive face mask CPAP in the DR
Time Frame
Within 30 minutes of birth
Title
Duration of PPV in the DR
Description
Duration of PPV in the DR
Time Frame
Within 30 minutes of birth
Title
The proportion of participants who are intubated in the DR
Description
The proportion of participants who are intubated in the DR
Time Frame
Within 30 minutes of birth
Title
The proportion of participants who receive chest compressions in the DR
Description
The proportion of participants who receive chest compressions in the DR
Time Frame
Within 30 minutes of birth
Title
The proportion of participants who receive volume in the DR
Description
The proportion of participants who receive volume in the DR
Time Frame
Within 30 minutes of birth
Title
The proportion of participants who receive adrenaline in the DR
Description
The proportion of participants who receive adrenaline in the DR
Time Frame
Within 30 minutes of birth
Title
Maximum FiO2 in the DR
Description
Maximum fraction of inspired oxygen (FiO2) in the DR
Time Frame
Within 20 minutes of birth
Title
Apgar score at 5 minutes
Description
Apgar score at 5 minutes (scale 0 -10, higher scores indicate better outcome)
Time Frame
5 minutes
Title
Apgar score at 10 minutes
Description
Apgar score at 10 minutes (scale 0 -10, higher scores indicate better outcome)
Time Frame
10 minutes
Title
Respiratory support in transport to NICU
Description
Respiratory support in transport to the neonatal intensive care unit (NICU)
Time Frame
Within 45 minutes of birth
Title
The proportion of participants who receive NCPAP in NICU
Description
The proportion of participants who receive nasal CPAP in NICU
Time Frame
Within one month
Title
The proportion of participants who receive endotracheal ventilation in NICU
Description
The proportion of participants who receive endotracheal ventilation in NICU
Time Frame
Within one month
Title
The proportion of participants who receive surfactant treatment
Description
The proportion of participants who receive surfactant treatment
Time Frame
Within one month
Title
The proportion of participants who have a pneumothorax drained
Description
The proportion of participants who have a pneumothorax drained
Time Frame
Within one month
Title
The proportion of participants who survive free of BPD
Description
The proportion of participants who are alive and not receiving respiratory support or supplemental oxygen on day 28 of life
Time Frame
Day 28 of life
Title
The proportion of participants who receive survive free of CLD
Description
The proportion of participants who are alive and not receiving respiratory support or supplemental oxygen at 36 weeks corrected age
Time Frame
36 weeks corrected
Title
The proportion of participants who receive postnatal steroids
Description
The proportion of participants who receive postnatal steroids
Time Frame
Through study completion, an average of 2-3 months in survivors
Title
The proportion of participants who receive home oxygen therapy
Description
The proportion of participants who receive home oxygen therapy
Time Frame
Through study completion, an average of 2-3 months in survivors
Title
The proportion of participants who die before hospital discharge
Description
The proportion of participants who die before hospital discharge
Time Frame
Through study completion, an average of 2-3 months in survivors
10. Eligibility
Sex
All
Minimum Age & Unit of Time
0 Minutes
Maximum Age & Unit of Time
5 Minutes
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Born before 32 weeks gestational age by best obstetric estimate
Exclusion Criteria:
Infants with major congenital anomalies
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Colm PF O'Donnell, PhD
Phone
35316373100
Ext
3186
Email
codonnell@nmh.ie
First Name & Middle Initial & Last Name or Official Title & Degree
Lisa K McCarthy, PhD
Phone
35316373100
Email
lmccarthy@nmh.ie
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Colm PF O'Donnell, PhD
Organizational Affiliation
National Maternity Hospital; University College Dublin
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Maternity Hospital
City
Dublin
ZIP/Postal Code
D02 YH21
Country
Ireland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Colm PF O'Donnell, PhD
Phone
35316373100
Ext
3186
Email
codonnell@nmh.ie
First Name & Middle Initial & Last Name & Degree
Lisa K McCarthy, PhD
Phone
35316373100
Email
lmccarthy@nmh.ie
First Name & Middle Initial & Last Name & Degree
Eoin M O Currain, PhD
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Anonymised data will be shared for studies approved by the chief and principal investigators
IPD Sharing Time Frame
Data will be available after the primary report of the study has been published and will be available for 5 years
IPD Sharing 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
Citations:
PubMed Identifier
26472855
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.
Results Reference
background
PubMed Identifier
20236659
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.
Results Reference
background
PubMed Identifier
31085675
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.
Results Reference
background
PubMed Identifier
29099872
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.
Results Reference
background
PubMed Identifier
31521774
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.
Results Reference
background
PubMed Identifier
32847832
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.
Results Reference
background
PubMed Identifier
27315509
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.
Results Reference
background
PubMed Identifier
15321956
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.
Results Reference
background
PubMed Identifier
24554040
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.
Results Reference
background
PubMed Identifier
5949048
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.
Results Reference
background
PubMed Identifier
6650989
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.
Results Reference
background
PubMed Identifier
7155672
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.
Results Reference
background
PubMed Identifier
2361419
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.
Results Reference
background
PubMed Identifier
22147285
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.
Results Reference
background
Learn more about this trial
Routine Or Selective Application of a Face Mask for Preterm Infants at Birth: the ROSA Trial
We'll reach out to this number within 24 hrs