SUPPORT: Surfactant Positive Airway Pressure and Pulse Oximetry Trial

• Sponsor: NICHD Neonatal Research Network (Other)
• Overall Status: Completed
• CT.gov ID: NCT00233324
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH), National Center for Research Resources (NCRR) (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
• Enrollment: 1,316
• Locations: 22
• Arms: 4
• Duration (Months): 138
• Patients Per Site: 59.8
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This study compared the use of continuous positive airway pressure initiated at birth with the early administration of surfactant administered through a tube in the windpipe within 1 hour of birth for premature infants born at 24 to 27 weeks gestation. In addition, these infants within 2 hours of birth, had a special pulse oximeter placed to continuously monitor their oxygen saturation in two different target ranges (85-89% or 91-95%). This study helped determine whether or not these two management strategies affect chronic lung disease and survival of premature infants.

Condition or Disease	Intervention/Treatment	Phase
Infant, Newborn, Diseases; Other Preterm Infants; Infant, Small for Gestational Age; Premature Birth; Bronchopulmonary Dysplasia; Retinopathy of Prematurity	Drug: Surfactant; Device: Continuous Positive Airway Pressure (CPAP); Drug: Supplemental oxygen with target saturation of 85 to 89%; Drug: Supplemental oxygen with target saturation of 91 to 95%	Phase 3

Detailed Description

Study subjects were infants of 24 0/7ths to 27 6/7th weeks at birth for which a decision has been made to provide full resuscitation as required. Infants 27 weeks or less gestation (completed weeks by best obstetric estimate) were enrolled because more than 80% of such infants in the Network are intubated, usually early in their neonatal course. The feasibility trial demonstrated that the five NICHD centers involved could reduce intubation in the delivery room to less than 50% of such infants if they are not intubated for surfactant. We excluded infants of 23 weeks or less in view of their extremely high mortality and morbidity, and their almost universal need for delivery room intubation for resuscitation. Secondary studies included: neuroimaging/MRI, growth, and breathing outcomes.

Strata: There were two randomization strata, infants of 24 0/7ths to 25 6/7ths weeks, and infants of 26 0/7ths-27 6/7ths weeks by best obstetrical estimate.

Randomization:

Randomization was stratified by gestational age group, occurred prior to delivery for consented deliveries, and was performed by utilizing specially prepared double-sealed envelopes. Deliveries were randomized as a unit, thus multiples, twins, triplets, etc. were randomized to the same arm of the trial.

Informed Consent:

Parents were approached prior to delivery for informed consent, and their infants enrolled at delivery.

Study Intervention: Mode of Ventilatory Support The intervention began after birth when the infant was given to the resuscitation team. The conduct of the resuscitation followed usual guidelines, and once stabilized, all Control infants in both strata received prophylactic/early surfactant (within one hour of age), whereas all Treatment infants were placed on CPAP/PEEP following stabilization, and were intubated only for resuscitation indications.

Pulse Oximeter Allocation:

Infants were randomized to receive either a high- or low-saturation of peripheral oxygen (SpO2) as monitored by a study oximeter immediately following NICU admission, with a maximum allowable delay of two hours following admission.

The SUPPORT Trial recruitment was temporarily paused on November 23, 2005 based on concern regarding pulse oximeter readings > 95% and due to concern regarding separation of the two arms of the oximetry portion of the study. Further analyses were performed which showed that infants on room air accounted for a significant portion of pulse oximetry saturations above 95%. Separation of the two groups was reanalyzed based on time spent in room air and the duration of time spent at individual SpO2 values, which both showed group differences. The trial was restarted on February 6, 2006.

Follow-up: Subjects will be seen for a follow-up visit at 18-22 months corrected age to look at neurodevelopment.

Extended follow-up: Subjects enrolled in the Neuroimaging/MRI secondary study will also be seen for a follow-up visit at 6-7 years to look at later school-age development. Subjects attending the 6-7 year follow-up visit will be invited to participate in this secondary study which will analyze the relationship of salivary cortisol and dehydroepiandrosterone (DHEA) to: (a) blood pressure and adiposity; (b) prenatal and postnatal growth; and (c) DNA methylation patterns.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1316 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT) in Extremely Low Birth Weight Infants
• Study Start Date: Feb 1, 2005
• Actual Primary Completion Date: Feb 1, 2009
• Actual Study Completion Date: Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Surfactant and Low Oxygen Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 85% to 89%	Drug: Surfactant; Intubation and administration of surfactant by 1 hour of age.; Drug: Supplemental oxygen with target saturation of 85 to 89%; Supplemental oxygen in the range of 85% to 89% until the infant is no longer requiring ventilatory support or oxygen; Other Names: Low oxygen
Experimental: Surfactant and High Oxygen Administration of surfactant by endotracheal tube and supplemental oxygen with target saturationof 91% to 95%	Drug: Surfactant; Intubation and administration of surfactant by 1 hour of age.; Drug: Supplemental oxygen with target saturation of 91 to 95%; Supplemental oxygen in the range of 91% to 95% until the infant is no longer requiring ventilatory support or oxygen.; Other Names: High oxygen
Experimental: CPAP and Low Oxygen Administration of continuous positive airway pressure (CPAP) and supplemental oxygen with target saturation of 85% to 89%	Device: Continuous Positive Airway Pressure (CPAP); Continuous Positive Airway Pressure/Positive End Expiratory Pressure (CPAP/PEEP) begun in the delivery room and continuing in the NICU; Other Names: CPAP ; Drug: Supplemental oxygen with target saturation of 85 to 89%; Supplemental oxygen in the range of 85% to 89% until the infant is no longer requiring ventilatory support or oxygen; Other Names: Low oxygen
Experimental: CPAP and High Oxygen Administration of continuous positive airway pressure (CPAP)and supplemental oxygen with target saturation of 91% to 95%	Device: Continuous Positive Airway Pressure (CPAP); Continuous Positive Airway Pressure/Positive End Expiratory Pressure (CPAP/PEEP) begun in the delivery room and continuing in the NICU; Other Names: CPAP ; Drug: Supplemental oxygen with target saturation of 91 to 95%; Supplemental oxygen in the range of 91% to 95% until the infant is no longer requiring ventilatory support or oxygen.; Other Names: High oxygen

Outcome Measures

Primary Outcome Measures

1. Survival Without Bronchopulmonary Dysplasia (BPD) [36 weeks]

2. Survival Without Severe Retinopathy of Prematurity (ROP) (Threshold Disease or the Need for Surgery) [55 weeks]

Secondary Outcome Measures

1. Death or Neurodevelopmental Impairment [18-22 months]

2. Duration of Mechanical Ventilation [Entire NICU stay, up to 120 days]

   The length in days that an individual was on mechanical ventilation which includes high frequency and conventional ventilation.

3. Survival Without Ventilation [From birth through first 7 days of life.]

   Surviving the first 7 days of life without any need for ventilation by day 7

4. Received Surfactant Treatment [From birth through 120 days of life.]

   Received any surfactant treatment.

5. Number of Participants With Air Leaks [From birth through first 14 days of life.]

   Number of participants with air leaks including pnemothorax, pulmonary interstitial emphysema (PIE), and pneumopericardium.

6. Physiological Bronchopulmonary Dysplasia [36 weeks post menstrual age.]

   Infants who received support via ventilator or CPAP at 36 weeks PMA. Alternatively, infants who received low levels of supplemental oxygen (<30%) at 36 weeks PMA may have been eligible for a physiologic challenge in which there was an attempt to wean the infant to room air. Specifically, infants were eligible for the challenge if at 36 weeks PMA if they were receiving effective oxygen <27% and had majority saturation >90%, or they were receiving effective oxygen 27-30% and had majority saturation >96%, or they were receiving room air by nasal cannula. The challenge took place between 36 and 37 weeks PMA. Those who were not challenged because their level of support increased (support with CPAP or ventilation or increased oxygen) were considered to have BPD, as were those who failed the challenge.

7. Death [18-22 months]

   Participants who died by their follow-up visit at 18-22 months.

8. Severe Intraventricular Hemorrhage (IVH) [From birth through first 120 days of life.]

   There are four grades of intraventricular hemorrhage: Grade I - echodensity/hemorrhage is confied to the germinal matrix. Grade II - echodensity/hemorrhage in the lateral ventricle(s) without distention. Grade III - echodensity/hemorrhage in the lateral ventricle(s) with distention. Grade IV - echodense lesion in the parenchyma. Severe IVH is defined as having IVH grades of III or IV.

9. Periventricular Leukomalacia (PVL) [From birth through first 120 days of life.]

   Increased echogenicity or cysts in periventricular region.

10. Threshold Retinopathy of Prematurity (ROP) Requiring Surgery [From birth through first 120 days of life.]

    Diagnosis of retinopathy of prematurity which resulted in requiring surgery.

11. Endotracheal Intubation [Delivery Room, post-delivery]

    Insertion of a tube into the trachea to allow positive pressure ventilation for breathing.

12. Duration of Oxygen Supplementation [From birth through first 120 days of life.]

    The length of time in days that a participant had oxygen supplementation.

13. Pulse Oximetry Values > 90% [From birth through first 120 days of life.]

    Percentage of time spent above 90% oxygen saturation.

14. Blindness in at Least One Eye [18-22 months]

    Blindness in at least one eye by 18-22 months of life.

15. Received Postnatal Steroids [From birth through first 120 days of life.]

    Participant received any doses or courses of systemic steroids to prevent or treat bronchopulmonary dysplasia/chronic lung disease.

16. Necrotizing Enterocolitis (NEC) [From birth through first 120 days of life.]

    Proven necrotizing enterocolitis (NEC) diagnosis using the Modified Bell's Staging Criteria for NEC.

17. Cerebral Palsy [18-22 months]

    Incidence of cerebral palsy.

Other Outcome Measures

1. Apgar Scores at 5 Minutes [5 minutes after birth.]

   Apgar stands for "Appearance, Pulse, Grimace, Activity, and Respiration" and scores range from 1 (worst) to 10 (best) indicating a baby's condition 5 minutes after birth.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 24 Weeks to 27 Weeks
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Infants with a minimal gestational age of 24 weeks 0 days to 27 completed weeks (up to 27 6/7ths) by best obstetrical estimate

• Infants who will receive full resuscitation as necessary, i.e., no parental request or physician decision to forego resuscitation

• Infants whose parents/legal guardians have provided consent for enrollment, or

• Infants without known major congenital malformations

Exclusion Criteria:

• Any infant transported to the center after delivery

• Infants whose parents/legal guardians refuse consent

• Infants born during a time when the research apparatus/study personnel are not available

• Infants < 24 weeks 0 days or > 28 weeks 0 days, completed weeks of gestation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	Stanford University	Palo Alto	California	United States	94304
3	University of California at San Diego	San Diego	California	United States	92103-8774
4	Yale University	New Haven	Connecticut	United States	06504
5	University of Miami	Miami	Florida	United States	33136
6	Emory University	Atlanta	Georgia	United States	30303
7	Indiana University	Indianapolis	Indiana	United States	46202
8	University of Iowa	Iowa City	Iowa	United States	52242
9	Tufts Medical Center	Boston	Massachusetts	United States	02111
10	Wayne State University	Detroit	Michigan	United States	48201
11	University of New Mexico	Albuquerque	New Mexico	United States	87131
12	University of Rochester	Rochester	New York	United States	14642
13	Wake Forest University	Charlotte	North Carolina	United States	27157
14	RTI International	Durham	North Carolina	United States	27705
15	Duke University	Durham	North Carolina	United States	27710
16	Cincinnati Children's Medical Center	Cincinnati	Ohio	United States	45267
17	Case Western Reserve University, Rainbow Babies and Children's Hospital	Cleveland	Ohio	United States	44106
18	Brown University, Women & Infants Hospital of Rhode Island	Providence	Rhode Island	United States	02905
19	University of Tennessee	Memphis	Tennessee	United States	38163
20	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas	United States	75235
21	University of Texas Health Science Center at Houston	Houston	Texas	United States	77030
22	University of Utah	Salt Lake City	Utah	United States	84108

Sponsors and Collaborators

• NICHD Neonatal Research Network
• National Heart, Lung, and Blood Institute (NHLBI)
• National Center for Research Resources (NCRR)
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Principal Investigator: Abbot R. Laptook, MD, Brown University, Women & Infants Hospital of Rhode Island
• Principal Investigator: Michele C. Walsh, MD MS, Case Western Reserve University, Rainbow Babies and Children's Hospital
• Principal Investigator: Ronald N. Goldberg, MD, Duke University
• Principal Investigator: Barbara J. Stoll, MD, Emory University
• Principal Investigator: Brenda B. Poindexter, MD MS, Indiana University
• Principal Investigator: Abhik Das, PhD, RTI International
• Principal Investigator: Krisa P. Van Meurs, MD, Stanford University
• Principal Investigator: Ivan D. Frantz III, MD, Tufts Medical Center
• Principal Investigator: Neil N. Finer, MD, University of California, San Diego
• Principal Investigator: Kurt Schibler, MD, Children's Hospital Medical Center, Cincinnati
• Principal Investigator: Waldemar A. Carlo, MD, University of Alabama at Birmingham
• Principal Investigator: Edward F. Bell, MD, University of Iowa
• Principal Investigator: Kristi L. Watterberg, MD, University of New Mexico
• Principal Investigator: Pablo J. Sanchez, MD, University of Texas, Southwestern Medical Center at Dallas
• Principal Investigator: Kathleen A. Kennedy, MD MPH, The University of Texas Health Science Center, Houston
• Principal Investigator: Roger G. Faix, MD, University of Utah
• Principal Investigator: Seetha Shankaran, MD, Wayne State University
• Principal Investigator: Richard A. Ehrenkranz, MD, Yale University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• NICHD Neonatal Research Network site
• NICHD Pregnancy & Perinatology Branch

Publications

• Deuticke B. Monocarboxylate transport in red blood cells: kinetics and chemical modification. Methods Enzymol. 1989;173:300-29.

• Responsible Party: NICHD Neonatal Research Network
• ClinicalTrials.gov Identifier: NCT00233324
• Other Study ID Numbers: NICHD-NRN-0033; U10HD021364; U10HD021373; U10HD021385; U10HD027851; U10HD027853; U10HD027856; U10HD027871; U10HD027880; U10HD027904; U10HD034216; U10HD036790; U10HD040461; U10HD040492; U10HD040689; U10HD053089; U10HD053109; U10HD053119; U10HD053124; UL1RR024128; UL1RR024139; UL1RR024979; UL1RR024982; UL1RR024989; UL1RR025008; M01RR000633; M01RR000750; M01RR008084; U10HD021397; U10HD040521; U10HD040498
• First Posted: Oct 5, 2005
• Last Update Posted: Apr 18, 2019
• Last Verified: Apr 1, 2019

• Keywords provided by NICHD Neonatal Research Network: NICHD Neonatal Research Network; Extremely Low Birth Weight (ELBW); Very Low Birth Weight (VLBW); Prematurity; Mechanical ventilation; Surfactant; Intubation; Neurodevelopmental impairment; Pulse oximetry; Oxygen saturation; Positive-Pressure Respiration
• Additional relevant MeSH terms: Bronchopulmonary Dysplasia; Retinopathy of Prematurity; Premature Birth; Infant, Newborn, Diseases; Birth Weight; Pulmonary Surfactants

Study Results

Participant Flow

Recruitment Details	3546 infants assessed for eligibility from 3127 pregnancies. 2230 were excluded for not meeting eligibility criteria or parental permission was not granted or other reasons.
Pre-assignment Detail	235 did not meet eligiblity criteria 125 did not have personnel or equipment available 699 were eligible did not have consent sought 344 were eligible but parent or guardian was not available 748 were eligible but parent or guardian denied permission to enroll 68 were eligible and had permission but were not randomized 11 had other reasons

Arm/Group Title	Early Surfactant and Lower Range Oxygen	Early Surfactant and Higher Range Oxygen	CPAP and Lower Range Oxygen	CPAP and Higher Range Oxygen
Arm/Group Description	Early Surfactant and 85-89% target oxygen saturation	Early Surfactant and 91-95% target oxygen saturation	Continuous Positive Airway Pressure (CPAP) and 85-89% target oxygen saturation	Continuous Positive Airway Pressure (CPAP) and 91-95% target oxygen saturation
Period Title: Main Study
STARTED	318	335	336	327
COMPLETED	250	275	274	280
NOT COMPLETED	68	60	62	47
Period Title: Main Study
STARTED	250	275	274	280
COMPLETED	237	261	256	269
NOT COMPLETED	13	14	18	11

Baseline Characteristics

Arm/Group Title	CPAP and Lower Range Oxygen	CPAP and Higher Range Oxygen	Early Surfactant and Lower Range Oxygen	Early Surfactant and Higher Range Oxygen	Total
Arm/Group Description	Continuous Positive Airway Pressure/Positive End Expiratory Pressure (CPAP/PEEP) begun in the delivery room and continuing in the NICU and oxygen administered in lower range (85-90%)	Continuous Positive Airway Pressure/Positive End Expiratory Pressure (CPAP/PEEP) begun in the delivery room and continuing in the NICU and oxygen adminstered in higher range (91-95%)	Intubation and administration of surfactant by 1 hour of age and oxygen adminstered in lower range (85-90%)	Intubation and administration of surfactant by 1 hour of age and oxygen adminstered in higher range (91-95%)	Total of all reporting groups
Overall Participants	336	327	318	335	1316
Age, Customized (participants) [Number]
>23 weeks and <28 weeks gestational age	336 100%	327 100%	318 100%	335 100%	1316 100%
Sex: Female, Male (Count of Participants)
Female	172 51.2%	149 45.6%	141 44.3%	142 42.4%	604 45.9%
Male	164 48.8%	178 54.4%	177 55.7%	193 57.6%	712 54.1%
Region of Enrollment (participants) [Number]
United States	336 100%	327 100%	318 100%	335 100%	1316 100%

Outcome Measures

1. Primary Outcome

Title	Survival Without Bronchopulmonary Dysplasia (BPD)
Time Frame	36 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CPAP	Surfactant
Arm/Group Description	Continuous Positive Airway Pressure/Positive End Expiratory Pressure (CPAP/PEEP) begun in the delivery room and continuing in the NICU	Intubation and administration of surfactant by 1 hour of age
Measure Participants	663	653
Number [Participants]	346 103%	320 97.9%

2. Primary Outcome

Title	Survival Without Severe Retinopathy of Prematurity (ROP) (Threshold Disease or the Need for Surgery)
Time Frame	55 weeks

Outcome Measure Data

Analysis Population Description

49 infants in the lower oxygen saturation group and 46 infants in the higher oxygen saturation group that had unknown retinopathy of prematurity outcome

Arm/Group Title	Lower Oxygen Saturation Target	Higher Oxygen Saturation Target
Arm/Group Description	SpO2 range (85% to 89%) until the infant is no longer requiring ventilatory support or oxygen.	SpO2 range (91% to 95%) until the infant is no longer requiring ventilatory support or oxygen.
Measure Participants	605	616
Number [participants]	434 129.2%	418 127.8%

3. Secondary Outcome

Title	Death or Neurodevelopmental Impairment
Time Frame	18-22 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CPAP	Surfactant	Lower Oxygen Saturation Target	Higher Oxygen Saturation Target
Arm/Group Description	Continuous Positive Airway Pressure/Positive End Expiratory Pressure (CPAP/PEEP) begun in the delivery room and continuing in the NICU	Intubation and administration of surfactant by 1 hour of age	SpO2 range (85% to 89%) until the infant is no longer requiring ventilatory support or oxygen.	SpO2 range (91% to 95%) until the infant is no longer requiring ventilatory support or oxygen.
Measure Participants	621	613	612	622
Number [participants]	173 51.5%	183 56%	185 58.2%	171 51%

4. Secondary Outcome

Title	Duration of Mechanical Ventilation
Description	The length in days that an individual was on mechanical ventilation which includes high frequency and conventional ventilation.
Time Frame	Entire NICU stay, up to 120 days

Outcome Measure Data

Analysis Population Description

1078 participants survived to discharge and they all had information available for regarding use of mechanical ventilation.

Arm/Group Title	Surfactant and Low Oxygen	Surfactant and High Oxygen	CPAP and Low Oxygen	CPAP and High Oxygen
Arm/Group Description	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 85% to 89%	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 91% to 95%	Administration of continuous positive airway pressure (CPAP) and supplemental oxygen with target saturation of 85% to 89%	Administration of continuous positive airway pressure (CPAP) and supplemental oxygen with target saturation of 91% to 95%
Measure Participants	249	275	274	280
Median (Inter-Quartile Range) [days]	11	13	7	11.5

5. Secondary Outcome

Title	Survival Without Ventilation
Description	Surviving the first 7 days of life without any need for ventilation by day 7
Time Frame	From birth through first 7 days of life.

Outcome Measure Data

Analysis Population Description

1307 participants had known survival and ventilation statuses. 9 participants were excluded due to unknown ventilation status from birth through 7 days of life: 6 infants in the lower oxygen group, 3 infants in the high oxygen group.

Arm/Group Title	Surfactant and Low Oxygen	Surfactant and High Oxygen	CPAP and Low Oxygen	CPAP and High Oxygen
Arm/Group Description	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 85% to 89%	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 91% to 95%	Administration of continuous positive airway pressure (CPAP) and supplemental oxygen with target saturation of 85% to 89%	Administration of continuous positive airway pressure (CPAP)and supplemental oxygen with target saturation of 91% to 95%
Measure Participants	317	335	331	324
Count of Participants [Participants]	161 47.9%	157 48%	190 59.7%	172 51.3%

6. Secondary Outcome

Title	Received Surfactant Treatment
Description	Received any surfactant treatment.
Time Frame	From birth through 120 days of life.

Outcome Measure Data

Analysis Population Description

1312 participants had known surfactant treatment. 4 were excluded due to unknown surfactant treatment: 2 infants in the low oxygen group, 2 infants in the high oxygen group.

Arm/Group Title	Surfactant and Low Oxygen	Surfactant and High Oxygen	CPAP and Low Oxygen	CPAP and High Oxygen
Arm/Group Description	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 85% to 89%	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 91% to 95%	Administration of continuous positive airway pressure (CPAP) and supplemental oxygen with target saturation of 85% to 89%	Administration of continuous positive airway pressure (CPAP)and supplemental oxygen with target saturation of 91% to 95%
Measure Participants	317	335	335	325
Count of Participants [Participants]	159 47.3%	176 53.8%	42 13.2%	51 15.2%

7. Secondary Outcome

Title	Number of Participants With Air Leaks
Description	Number of participants with air leaks including pnemothorax, pulmonary interstitial emphysema (PIE), and pneumopericardium.
Time Frame	From birth through first 14 days of life.

Outcome Measure Data

Analysis Population Description

All 1316 participants had data on incidence of air leaks.

Arm/Group Title	Surfactant and Low Oxygen	Surfactant and High Oxygen	CPAP and Low Oxygen	CPAP and High Oxygen
Arm/Group Description	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 85% to 89%	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 91% to 95%	Administration of continuous positive airway pressure (CPAP) and supplemental oxygen with target saturation of 85% to 89%	Administration of continuous positive airway pressure (CPAP)and supplemental oxygen with target saturation of 91% to 95%
Measure Participants	318	335	336	327
Count of Participants [Participants]	26 7.7%	22 6.7%	25 7.9%	20 6%

8. Secondary Outcome

Title	Physiological Bronchopulmonary Dysplasia
Description	Infants who received support via ventilator or CPAP at 36 weeks PMA. Alternatively, infants who received low levels of supplemental oxygen (<30%) at 36 weeks PMA may have been eligible for a physiologic challenge in which there was an attempt to wean the infant to room air. Specifically, infants were eligible for the challenge if at 36 weeks PMA if they were receiving effective oxygen <27% and had majority saturation >90%, or they were receiving effective oxygen 27-30% and had majority saturation >96%, or they were receiving room air by nasal cannula. The challenge took place between 36 and 37 weeks PMA. Those who were not challenged because their level of support increased (support with CPAP or ventilation or increased oxygen) were considered to have BPD, as were those who failed the challenge.
Time Frame	36 weeks post menstrual age.

Outcome Measure Data

Analysis Population Description

1108 participants survived to 36 weeks and had BPD information. 208 participants did not survive to 36 weeks and were excluded: 114 from the low oxygen group, 94 from the high oxygen group.

Arm/Group Title	Surfactant and Low Oxygen	Surfactant and High Oxygen	CPAP and Low Oxygen	CPAP and High Oxygen
Arm/Group Description	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 85% to 89%	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 91% to 95%	Administration of continuous positive airway pressure (CPAP) and supplemental oxygen with target saturation of 85% to 89%	Administration of continuous positive airway pressure (CPAP)and supplemental oxygen with target saturation of 91% to 95%
Measure Participants	258	281	282	287
Count of Participants [Participants]	102 30.4%	117 35.8%	103 32.4%	120 35.8%

9. Secondary Outcome

Title	Death
Description	Participants who died by their follow-up visit at 18-22 months.
Time Frame	18-22 months

Outcome Measure Data

Analysis Population Description

1281 participants with confirmed deaths or survivals by follow-up. 35 were excluded due to incomplete follow-up visits: 21 in low oxygen group, 14 in high oxygen group.

Arm/Group Title	Surfactant and Low Oxygen	Surfactant and High Oxygen	CPAP and Low Oxygen	CPAP and High Oxygen
Arm/Group Description	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 85% to 89%	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 91% to 95%	Administration of continuous positive airway pressure (CPAP) and supplemental oxygen with target saturation of 85% to 89%	Administration of continuous positive airway pressure (CPAP)and supplemental oxygen with target saturation of 91% to 95%
Measure Participants	310	328	323	320
Count of Participants [Participants]	73 21.7%	67 20.5%	67 21.1%	51 15.2%

10. Secondary Outcome

Title	Severe Intraventricular Hemorrhage (IVH)
Description	There are four grades of intraventricular hemorrhage: Grade I - echodensity/hemorrhage is confied to the germinal matrix. Grade II - echodensity/hemorrhage in the lateral ventricle(s) without distention. Grade III - echodensity/hemorrhage in the lateral ventricle(s) with distention. Grade IV - echodense lesion in the parenchyma. Severe IVH is defined as having IVH grades of III or IV.
Time Frame	From birth through first 120 days of life.

Outcome Measure Data

Analysis Population Description

1270 participants had known IVH grades. 46 were excluded due to unknown IVH status: 24 infants from the low oxygen group, 22 infants from high oxygen group.

Arm/Group Title	Surfactant and Low Oxygen	Surfactant and High Oxygen	CPAP and Low Oxygen	CPAP and High Oxygen
Arm/Group Description	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 85% to 89%	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 91% to 95%	Administration of continuous positive airway pressure (CPAP) and supplemental oxygen with target saturation of 85% to 89%	Administration of continuous positive airway pressure (CPAP)and supplemental oxygen with target saturation of 91% to 95%
Measure Participants	307	321	323	319
Count of Participants [Participants]	34 10.1%	38 11.6%	49 15.4%	43 12.8%

11. Secondary Outcome

Title	Periventricular Leukomalacia (PVL)
Description	Increased echogenicity or cysts in periventricular region.
Time Frame	From birth through first 120 days of life.

Outcome Measure Data

Analysis Population Description

1272 participants had known PVL statuses. 44 were excluded due to unknown PVL status: 23 infants in the low oxygen group, 21 infants in the high oxygen group.

Arm/Group Title	Surfactant and Low Oxygen	Surfactant and High Oxygen	CPAP and Low Oxygen	CPAP and High Oxygen
Arm/Group Description	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 85% to 89%	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 91% to 95%	Administration of continuous positive airway pressure (CPAP) and supplemental oxygen with target saturation of 85% to 89%	Administration of continuous positive airway pressure (CPAP)and supplemental oxygen with target saturation of 91% to 95%
Measure Participants	307	322	324	319
Count of Participants [Participants]	10 3%	16 4.9%	14 4.4%	14 4.2%

12. Secondary Outcome

Title	Threshold Retinopathy of Prematurity (ROP) Requiring Surgery
Description	Diagnosis of retinopathy of prematurity which resulted in requiring surgery.
Time Frame	From birth through first 120 days of life.

Outcome Measure Data

Analysis Population Description

997 surviving participants with ROP data were included. 319 total participants were excluded due to death (N=224) or missing ROP data (N=95): 171 in the low oxygen group, 148 in the high oxygen group.

Arm/Group Title	Surfactant and Low Oxygen	Surfactant and High Oxygen	CPAP and Low Oxygen	CPAP and High Oxygen
Arm/Group Description	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 85% to 89%	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 91% to 95%	Administration of continuous positive airway pressure (CPAP) and supplemental oxygen with target saturation of 85% to 89%	Administration of continuous positive airway pressure (CPAP)and supplemental oxygen with target saturation of 91% to 95%
Measure Participants	230	250	253	264
Count of Participants [Participants]	19 5.7%	44 13.5%	17 5.3%	47 14%

13. Secondary Outcome

Title	Endotracheal Intubation
Description	Insertion of a tube into the trachea to allow positive pressure ventilation for breathing.
Time Frame	Delivery Room, post-delivery

Outcome Measure Data

Analysis Population Description

1312 participants had non-missing data on whether they experienced endotracheal intubation. 4 participants were excluded due to missing information: 2 infants in the low oxygen group, 2 infants in the high oxygen group.

Arm/Group Title	Surfactant and Low Oxygen	Surfactant and High Oxygen	CPAP and Low Oxygen	CPAP and High Oxygen
Arm/Group Description	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 85% to 89%	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 91% to 95%	Administration of continuous positive airway pressure (CPAP) and supplemental oxygen with target saturation of 85% to 89%	Administration of continuous positive airway pressure (CPAP)and supplemental oxygen with target saturation of 91% to 95%
Measure Participants	317	335	335	325
Count of Participants [Participants]	294 87.5%	315 96.3%	110 34.6%	117 34.9%

14. Secondary Outcome

Title	Duration of Oxygen Supplementation
Description	The length of time in days that a participant had oxygen supplementation.
Time Frame	From birth through first 120 days of life.

Outcome Measure Data

Analysis Population Description

1078 participants survived to discharge and they all had information available regarding the duration of their oxygen supplementation.

Arm/Group Title	Surfactant and Low Oxygen	Surfactant and High Oxygen	CPAP and Low Oxygen	CPAP and High Oxygen
Arm/Group Description	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 85% to 89%	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 91% to 95%	Administration of continuous positive airway pressure (CPAP) and supplemental oxygen with target saturation of 85% to 89%	Administration of continuous positive airway pressure (CPAP)and supplemental oxygen with target saturation of 91% to 95%
Measure Participants	249	275	274	280
Median (Inter-Quartile Range) [days]	46	60	43	59

15. Secondary Outcome

Title	Pulse Oximetry Values > 90%
Description	Percentage of time spent above 90% oxygen saturation.
Time Frame	From birth through first 120 days of life.

Outcome Measure Data

Analysis Population Description

90 were excluded due to incomplete data: 48 from the low oxygen saturation group and 42 from the high oxygen saturation group.

Arm/Group Title	Surfactant and Low Oxygen	Surfactant and High Oxygen	CPAP and Low Oxygen	CPAP and High Oxygen
Arm/Group Description	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 85% to 89%	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 91% to 95%	Administration of continuous positive airway pressure (CPAP) and supplemental oxygen with target saturation of 85% to 89%	Administration of continuous positive airway pressure (CPAP)and supplemental oxygen with target saturation of 91% to 95%
Measure Participants	302	314	304	306
Median (Inter-Quartile Range) [percentage of time]	62	76	63	77

16. Secondary Outcome

Title	Blindness in at Least One Eye
Description	Blindness in at least one eye by 18-22 months of life.
Time Frame	18-22 months

Outcome Measure Data

Analysis Population Description

990 participants survived and were seen at the 18-22 month follow-up. 326 were excluded: 175 in the low oxygen group, 151 in the high oxygen group.

Arm/Group Title	Surfactant and Low Oxygen	Surfactant and High Oxygen	CPAP and Low Oxygen	CPAP and High Oxygen
Arm/Group Description	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 85% to 89%	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 91% to 95%	Administration of continuous positive airway pressure (CPAP) and supplemental oxygen with target saturation of 85% to 89%	Administration of continuous positive airway pressure (CPAP)and supplemental oxygen with target saturation of 91% to 95%
Measure Participants	225	254	254	257
Count of Participants [Participants]	4 1.2%	3 0.9%	1 0.3%	5 1.5%

17. Secondary Outcome

Title	Received Postnatal Steroids
Description	Participant received any doses or courses of systemic steroids to prevent or treat bronchopulmonary dysplasia/chronic lung disease.
Time Frame	From birth through first 120 days of life.

Outcome Measure Data

Analysis Population Description

1280 participants had information regarding whether they received postnatal steroids. 36 participants were excluded due to missing data: 18 infants in the low oxygen group, 18 infants in the high oxygen group.

Arm/Group Title	Surfactant and Low Oxygen	Surfactant and High Oxygen	CPAP and Low Oxygen	CPAP and High Oxygen
Arm/Group Description	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 85% to 89%	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 91% to 95%	Administration of continuous positive airway pressure (CPAP) and supplemental oxygen with target saturation of 85% to 89%	Administration of continuous positive airway pressure (CPAP)and supplemental oxygen with target saturation of 91% to 95%
Measure Participants	308	323	328	321
Count of Participants [Participants]	42 12.5%	41 12.5%	19 6%	28 8.4%

18. Secondary Outcome

Title	Necrotizing Enterocolitis (NEC)
Description	Proven necrotizing enterocolitis (NEC) diagnosis using the Modified Bell's Staging Criteria for NEC.
Time Frame	From birth through first 120 days of life.

Outcome Measure Data

Analysis Population Description

1290 participants had known NEC statuses. 26 were excluded due to missing NEC data: 13 infants in the low oxygen group, 13 infants in the high oxygen group.

Arm/Group Title	Surfactant and Low Oxygen	Surfactant and High Oxygen	CPAP and Low Oxygen	CPAP and High Oxygen
Arm/Group Description	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 85% to 89%	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 91% to 95%	Administration of continuous positive airway pressure (CPAP) and supplemental oxygen with target saturation of 85% to 89%	Administration of continuous positive airway pressure (CPAP)and supplemental oxygen with target saturation of 91% to 95%
Measure Participants	311	325	330	324
Count of Participants [Participants]	36 10.7%	27 8.3%	40 12.6%	43 12.8%

19. Secondary Outcome

Title	Cerebral Palsy
Description	Incidence of cerebral palsy.
Time Frame	18-22 months

Outcome Measure Data

Analysis Population Description

990 participants survived and were seen at the 18-22 month follow-up. 326 were excluded: 175 in the low oxygen group, 151 in the high oxygen group.

Arm/Group Title	Surfactant and Low Oxygen	Surfactant and High Oxygen	CPAP and Low Oxygen	CPAP and High Oxygen
Arm/Group Description	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 85% to 89%	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 91% to 95%	Administration of continuous positive airway pressure (CPAP) and supplemental oxygen with target saturation of 85% to 89%	Administration of continuous positive airway pressure (CPAP)and supplemental oxygen with target saturation of 91% to 95%
Measure Participants	225	254	254	257
Count of Participants [Participants]	17 5.1%	17 5.2%	26 8.2%	24 7.2%

20. Other Pre-specified Outcome

Title	Apgar Scores at 5 Minutes
Description	Apgar stands for "Appearance, Pulse, Grimace, Activity, and Respiration" and scores range from 1 (worst) to 10 (best) indicating a baby's condition 5 minutes after birth.
Time Frame	5 minutes after birth.

Outcome Measure Data

Analysis Population Description

All 1316 participants had APGAR scores at 5 minutes.

Arm/Group Title	Surfactant and Low Oxygen	Surfactant and High Oxygen	CPAP and Low Oxygen	CPAP and High Oxygen
Arm/Group Description	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 85% to 89%	Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 91% to 95%	Administration of continuous positive airway pressure (CPAP) and supplemental oxygen with target saturation of 85% to 89%	Administration of continuous positive airway pressure (CPAP)and supplemental oxygen with target saturation of 91% to 95%
Measure Participants	318	335	336	327
Median (Inter-Quartile Range) [scores on a scale]	7	7	7	7

Adverse Events

Arm/Group Title	Surfactant and Lower Range Oxygen		Surfactant and Higher Range Oxygen		CPAP and Lower Range Oxygen		CPAP and Higher Range Oxygen
Arm/Group Description	Early Surfactant and 85-89% target oxygen saturation		Early Surfactant and 91-95% target oxygen saturation		Continuous Positive Airway Pressure (CPAP) and 85-89% target oxygen saturation		Continuous Positive Airway Pressure (CPAP) and 91-95% target oxygen saturation
All Cause Mortality
	Surfactant and Lower Range Oxygen		Surfactant and Higher Range Oxygen		CPAP and Lower Range Oxygen		CPAP and Higher Range Oxygen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Surfactant and Lower Range Oxygen		Surfactant and Higher Range Oxygen		CPAP and Lower Range Oxygen		CPAP and Higher Range Oxygen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	204/318 (64.2%)		227/335 (67.8%)		231/336 (68.8%)		224/327 (68.5%)
Cardiac disorders
Chest compressions or drugs in the delivery room	22/318 (6.9%)		24/335 (7.2%)		19/333 (5.7%)		17/327 (5.2%)
Patent Ductus Aretriosus	151/311 (48.6%)		160/325 (49.2%)		156/330 (47.3%)		164/323 (50.8%)
Gastrointestinal disorders
Necrotizing enterocolitis	36/311 (11.6%)		27/325 (8.3%)		40/330 (12.1%)		43/324 (13.3%)
General disorders
Death	68/318 (21.4%)		60/335 (17.9%)		62/336 (18.5%)		47/327 (14.4%)
Nervous system disorders
Intraventricular hemorrhage (IVH) Grade 3 or 4	34/307 (11.1%)		38/321 (11.8%)		49/323 (15.2%)		43/319 (13.5%)
Respiratory, thoracic and mediastinal disorders
Air leak during initial 14 days	26/318 (8.2%)		22/335 (6.6%)		25/336 (7.4%)		20/327 (6.1%)
Pulmonary Hemorrhage	24/311 (7.7%)		21/325 (6.5%)		20/330 (6.1%)		13/324 (4%)
Nasal Breakdown	0/318 (0%)		1/335 (0.3%)		0/336 (0%)		1/327 (0.3%)
Other (Not Including Serious) Adverse Events
	Surfactant and Lower Range Oxygen		Surfactant and Higher Range Oxygen		CPAP and Lower Range Oxygen		CPAP and Higher Range Oxygen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/318 (1.3%)		5/335 (1.5%)		11/336 (3.3%)		7/327 (2.1%)
General disorders
Any other non-serious adverse event	0/318 (0%)		2/335 (0.6%)		1/336 (0.3%)		1/327 (0.3%)
Respiratory, thoracic and mediastinal disorders
Nasal Breakdown	4/318 (1.3%)		3/335 (0.9%)		10/336 (3%)		6/327 (1.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.