Infant, Newborn, DiseasesPhase 3SUPPORTNCT00233324
Surfactant Positive Airway Pressure and Pulse Oximetry Trial
A Phase 3 study testing Surfactant, Continuous Positive Airway Pressure (CPAP) and Supplemental oxygen with target saturation of 85 to 89% in people with Infant, Newborn, Diseases and Other Preterm Infants, run by NICHD Neonatal Research Network at 22 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 24 to 27 weeks
- Conditions the study is for
- Infant, Newborn, Diseases, Other Preterm Infants, Infant, Small for Gestational Age
- What is being tested?
- Surfactant, Continuous Positive Airway Pressure (CPAP) and Supplemental oxygen with target saturation of 85 to 89%
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,316 participants
- Where
- 22 sitesUnited States
- Study dates
- Feb 2005to Aug 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 24 to 27 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
22 sites in 1 country.
22 sites in 1 country
United States22 sites
University of New Mexico
Albuquerque, New Mexico, 87131
Emory University
Atlanta, Georgia, 30303
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Tufts Medical Center
Boston, Massachusetts, 02111
Wake Forest University
Charlotte, North Carolina, 27157
Cincinnati Children's Medical Center
Cincinnati, Ohio, 45267
Case Western Reserve University, Rainbow Babies and Children's Hospital
Cleveland, Ohio, 44106
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75235
Wayne State University
Detroit, Michigan, 48201
RTI International
Durham, North Carolina, 27705
Duke University
Durham, North Carolina, 27710
University of Texas Health Science Center at Houston
Houston, Texas, 77030
Indiana University
Indianapolis, Indiana, 46202
University of Iowa
Iowa City, Iowa, 52242
University of Tennessee
Memphis, Tennessee, 38163
University of Miami
Miami, Florida, 33136
Yale University
New Haven, Connecticut, 06504
Stanford University
Palo Alto, California, 94304
Brown University, Women & Infants Hospital of Rhode Island
Providence, Rhode Island, 02905
University of Rochester
Rochester, New York, 14642
University of Utah
Salt Lake City, Utah, 84108
University of California at San Diego
San Diego, California, 92103-8774
About this study
Official title: Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT) in Extremely Low Birth Weight Infants
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.
Read the 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.
- Conditions
- Infant, Newborn, Diseases, Other Preterm Infants, Infant, Small for Gestational Age, Premature Birth, Bronchopulmonary Dysplasia, Retinopathy of Prematurity
- Being tested
- Surfactant, Continuous Positive Airway Pressure (CPAP), Supplemental oxygen with target saturation of 85 to 89%, Supplemental oxygen with target saturation of 91 to 95%
- Keywords
- 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
- Medical subject headings
- Infant, Newborn, Diseases, Premature Birth, Bronchopulmonary Dysplasia, Retinopathy of Prematurity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SurfactantDrug
Intubation and administration of surfactant by 1 hour of age.
Continuous Positive Airway Pressure (CPAP)Device
Also called CPAP
Continuous Positive Airway Pressure/Positive End Expiratory Pressure (CPAP/PEEP) begun in the delivery room and continuing in the NICU
Supplemental oxygen with target saturation of 85 to 89%Drug
Also called Low oxygen
Supplemental oxygen in the range of 85% to 89% until the infant is no longer requiring ventilatory support or oxygen
Supplemental oxygen with target saturation of 91 to 95%Drug
Also called High oxygen
Supplemental oxygen in the range of 91% to 95% until the infant is no longer requiring ventilatory support or oxygen.
| Study group | Role | What they receive |
|---|---|---|
| Surfactant and Low Oxygen | Experimental | Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 85% to 89% Receives: Drug: Surfactant; Drug: Supplemental oxygen with target saturation of 85 to 89% |
| Surfactant and High Oxygen | Experimental | Administration of surfactant by endotracheal tube and supplemental oxygen with target saturationof 91% to 95% Receives: Drug: Surfactant; Drug: Supplemental oxygen with target saturation of 91 to 95% |
| CPAP and Low Oxygen | Experimental | Administration of continuous positive airway pressure (CPAP) and supplemental oxygen with target saturation of 85% to 89% Receives: Device: Continuous Positive Airway Pressure (CPAP); Drug: Supplemental oxygen with target saturation of 85 to 89% |
| CPAP and High Oxygen | Experimental | Administration of continuous positive airway pressure (CPAP)and supplemental oxygen with target saturation of 91% to 95% Receives: Device: Continuous Positive Airway Pressure (CPAP); Drug: Supplemental oxygen with target saturation of 91 to 95% |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival Without Bronchopulmonary Dysplasia (BPD)
Measured: 36 weeks
Survival Without Severe Retinopathy of Prematurity (ROP) (Threshold Disease or the Need for Surgery)
Measured: 55 weeks
Secondary outcomes (17)
Death or Neurodevelopmental Impairment
Measured: 18-22 months
Duration of Mechanical Ventilation
The length in days that an individual was on mechanical ventilation which includes high frequency and conventional ventilation.
Measured: Entire NICU stay, up to 120 days
Survival Without Ventilation
Surviving the first 7 days of life without any need for ventilation by day 7
Measured: From birth through first 7 days of life.
Received Surfactant Treatment
Received any surfactant treatment.
Measured: From birth through 120 days of life.
Number of Participants With Air Leaks
Number of participants with air leaks including pnemothorax, pulmonary interstitial emphysema (PIE), and pneumopericardium.
Measured: From birth through first 14 days of life.
Physiological Bronchopulmonary Dysplasia
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.
Measured: 36 weeks post menstrual age.
Death
Participants who died by their follow-up visit at 18-22 months.
Measured: 18-22 months
Severe Intraventricular Hemorrhage (IVH)
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.
Measured: From birth through first 120 days of life.
Periventricular Leukomalacia (PVL)
Increased echogenicity or cysts in periventricular region.
Measured: From birth through first 120 days of life.
Threshold Retinopathy of Prematurity (ROP) Requiring Surgery
Diagnosis of retinopathy of prematurity which resulted in requiring surgery.
Measured: From birth through first 120 days of life.
Endotracheal Intubation
Insertion of a tube into the trachea to allow positive pressure ventilation for breathing.
Measured: Delivery Room, post-delivery
Duration of Oxygen Supplementation
The length of time in days that a participant had oxygen supplementation.
Measured: From birth through first 120 days of life.
Pulse Oximetry Values > 90%
Percentage of time spent above 90% oxygen saturation.
Measured: From birth through first 120 days of life.
Blindness in at Least One Eye
Blindness in at least one eye by 18-22 months of life.
Measured: 18-22 months
Received Postnatal Steroids
Participant received any doses or courses of systemic steroids to prevent or treat bronchopulmonary dysplasia/chronic lung disease.
Measured: From birth through first 120 days of life.
Necrotizing Enterocolitis (NEC)
Proven necrotizing enterocolitis (NEC) diagnosis using the Modified Bell's Staging Criteria for NEC.
Measured: From birth through first 120 days of life.
Cerebral Palsy
Incidence of cerebral palsy.
Measured: 18-22 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2005 (estimated)
- Study startFeb 2005
- Primary completionFeb 2009
- Study completionAug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for Infant, Newborn, DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 1,316 participants (actual)
Sponsor and investigators
- Lead sponsor
- NICHD Neonatal Research Network
- Sponsor type
- Research network
- Collaborators
- 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)
- Responsible party
- Sponsor
- Investigators
- Abbot R. Laptook, MD, Principal investigator, Brown University, Women & Infants Hospital of Rhode IslandMichele C. Walsh, MD MS, Principal investigator, Case Western Reserve University, Rainbow Babies and Children's HospitalRonald N. Goldberg, MD, Principal investigator, Duke UniversityBarbara J. Stoll, MD, Principal investigator, Emory UniversityBrenda B. Poindexter, MD MS, Principal investigator, Indiana UniversityAbhik Das, PhD, Principal investigator, RTI InternationalKrisa P. Van Meurs, MD, Principal investigator, Stanford UniversityIvan D. Frantz III, MD, Principal investigator, Tufts Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00233324
- Sponsor's protocol ID
- NICHD-NRN-0033
- Other IDs
- U10HD021364, U10HD021373, U10HD021385, U10HD027851, U10HD027853, U10HD027856, U10HD027871, U10HD027880
- Acronym
- SUPPORT
- Status last verified
- Apr 2019
- First submitted
- 3 Oct 2005
- Last updated
- 18 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Deuticke B. Monocarboxylate transport in red blood cells: kinetics and chemical modification. Methods Enzymol. 1989;173:300-29. doi: 10.1016/s0076-6879(89)73020-2. No abstract available.
PubMed 2674614SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network; Carlo WA, Finer NN, Walsh MC, Rich W, Gantz MG, Laptook AR, Yoder BA, Faix RG, Das A, Poole WK, Schibler K, Newman NS, Ambalavanan N, Frantz ID 3rd, Piazza AJ, Sanchez PJ, Morris BH, Laroia N, Phelps DL, Poindexter BB, Cotten CM, Van Meurs KP, Duara S, Narendran V, Sood BG, O'Shea TM, Bell EF, Ehrenkranz RA, Watterberg KL, Higgins RD. Target ranges of oxygen saturation in extremely preterm infants. N Engl J Med. 2010 May 27;362(21):1959-69. doi: 10.1056/NEJMoa0911781. Epub 2010 May 16.
PubMed 20472937SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network; Finer NN, Carlo WA, Walsh MC, Rich W, Gantz MG, Laptook AR, Yoder BA, Faix RG, Das A, Poole WK, Donovan EF, Newman NS, Ambalavanan N, Frantz ID 3rd, Buchter S, Sanchez PJ, Kennedy KA, Laroia N, Poindexter BB, Cotten CM, Van Meurs KP, Duara S, Narendran V, Sood BG, O'Shea TM, Bell EF, Bhandari V, Watterberg KL, Higgins RD. Early CPAP versus surfactant in extremely preterm infants. N Engl J Med. 2010 May 27;362(21):1970-9. doi: 10.1056/NEJMoa0911783. Epub 2010 May 16.
PubMed 20472939Rich WD, Auten KJ, Gantz MG, Hale EC, Hensman AM, Newman NS, Finer NN; National Institute of Child Health and Human Development Neonatal Research Network. Antenatal consent in the SUPPORT trial: challenges, costs, and representative enrollment. Pediatrics. 2010 Jul;126(1):e215-21. doi: 10.1542/peds.2009-3353. Epub 2010 Jun 29.
PubMed 20587676Di Fiore JM, Walsh M, Wrage L, Rich W, Finer N, Carlo WA, Martin RJ; SUPPORT Study Group of Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Low oxygen saturation target range is associated with increased incidence of intermittent hypoxemia. J Pediatr. 2012 Dec;161(6):1047-52. doi: 10.1016/j.jpeds.2012.05.046. Epub 2012 Jun 26.
PubMed 22738947Rich W, Finer NN, Gantz MG, Newman NS, Hensman AM, Hale EC, Auten KJ, Schibler K, Faix RG, Laptook AR, Yoder BA, Das A, Shankaran S; SUPPORT and Generic Database Subcommittees of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Enrollment of extremely low birth weight infants in a clinical research study may not be representative. Pediatrics. 2012 Mar;129(3):480-4. doi: 10.1542/peds.2011-2121. Epub 2012 Feb 27.
PubMed 22371462Ambalavanan N, Carlo WA, Wrage LA, Das A, Laughon M, Cotten CM, Kennedy KA, Laptook AR, Shankaran S, Walsh MC, Higgins RD; SUPPORT Study Group of the NICHD Neonatal Research Network. PaCO2 in surfactant, positive pressure, and oxygenation randomised trial (SUPPORT). Arch Dis Child Fetal Neonatal Ed. 2015 Mar;100(2):F145-9. doi: 10.1136/archdischild-2014-306802. Epub 2014 Nov 25.
PubMed 25425651Navarrete CT, Wrage LA, Carlo WA, Walsh MC, Rich W, Gantz MG, Das A, Schibler K, Newman NS, Piazza AJ, Poindexter BB, Shankaran S, Sanchez PJ, Morris BH, Frantz ID 3rd, Van Meurs KP, Cotten CM, Ehrenkranz RA, Bell EF, Watterberg KL, Higgins RD, Duara S; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Growth Outcomes of Preterm Infants Exposed to Different Oxygen Saturation Target Ranges from Birth. J Pediatr. 2016 Sep;176:62-68.e4. doi: 10.1016/j.jpeds.2016.05.070. Epub 2016 Jun 22.
PubMed 27344218Stevens TP, Finer NN, Carlo WA, Szilagyi PG, Phelps DL, Walsh MC, Gantz MG, Laptook AR, Yoder BA, Faix RG, Newman JE, Das A, Do BT, Schibler K, Rich W, Newman NS, Ehrenkranz RA, Peralta-Carcelen M, Vohr BR, Wilson-Costello DE, Yolton K, Heyne RJ, Evans PW, Vaucher YE, Adams-Chapman I, McGowan EC, Bodnar A, Pappas A, Hintz SR, Acarregui MJ, Fuller J, Goldstein RF, Bauer CR, O'Shea TM, Myers GJ, Higgins RD; SUPPORT Study Group of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Respiratory outcomes of the surfactant positive pressure and oximetry randomized trial (SUPPORT). J Pediatr. 2014 Aug;165(2):240-249.e4. doi: 10.1016/j.jpeds.2014.02.054. Epub 2014 Apr 13.
PubMed 24725582Vaucher YE, Peralta-Carcelen M, Finer NN, Carlo WA, Gantz MG, Walsh MC, Laptook AR, Yoder BA, Faix RG, Das A, Schibler K, Rich W, Newman NS, Vohr BR, Yolton K, Heyne RJ, Wilson-Costello DE, Evans PW, Goldstein RF, Acarregui MJ, Adams-Chapman I, Pappas A, Hintz SR, Poindexter B, Dusick AM, McGowan EC, Ehrenkranz RA, Bodnar A, Bauer CR, Fuller J, O'Shea TM, Myers GJ, Higgins RD; SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network. Neurodevelopmental outcomes in the early CPAP and pulse oximetry trial. N Engl J Med. 2012 Dec 27;367(26):2495-504. doi: 10.1056/NEJMoa1208506.
PubMed 23268664Hintz SR, Bann CM, Vohr BR, McGowan EC, Vaucher YE, Fuller MG, Das A, Wilson-Costello DE, Garey DM, Sibley CK, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Neonatal Neuroimaging Among Children Born Extremely Preterm and Motor Coordination Impairment at School-Age. J Pediatr. 2025 Oct;285:114704. doi: 10.1016/j.jpeds.2025.114704. Epub 2025 Jun 24.
PubMed 40571094Lowe J, Bann CM, Dempsey AG, Fuller J, Taylor HG, Gustafson KE, Watson VE, Vohr BR, Das A, Shankaran S, Yolton K, Ball MB, Hintz SR; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Do Bayley-III Composite Scores at 18-22 Months Corrected Age Predict Full-Scale IQ at 6-7 Years in Children Born Extremely Preterm? J Pediatr. 2023 Dec;263:113700. doi: 10.1016/j.jpeds.2023.113700. Epub 2023 Aug 26.
PubMed 37640232Lowe J, Fuller JF, Dempsey AG, Do B, Bann CM, Das A, Gustafson KE, Vohr BR, Hintz SR, Watterberg KL; SUPPORT NEURO School-Age Study Subcommittee of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Cortisol awakening response and developmental outcomes at 6-7 years in children born extremely preterm. Pediatr Res. 2023 Feb;93(3):689-695. doi: 10.1038/s41390-022-02113-9. Epub 2022 Jun 17.
PubMed 35715492Duncan AF, Bann CM, Dempsey AG, Adams-Chapman I, Heyne R, Hintz SR; Eunice Kennedy Shriver National Institute of Child Health and Development Neonatal Research Network. Neuroimaging and Bayley-III correlates of early hand function in extremely preterm children. J Perinatol. 2019 Mar;39(3):488-496. doi: 10.1038/s41372-019-0314-0. Epub 2019 Jan 28.
PubMed 30692613Duncan AF, Bann CM, Dempsey A, Peralta-Carcelen M, Hintz S; Eunice Kennedy Shriver National Institute of Child Health and Development Neonatal Research Network. Behavioral Deficits at 18-22 Months of Age Are Associated with Early Cerebellar Injury and Cognitive and Language Performance in Children Born Extremely Preterm. J Pediatr. 2019 Jan;204:148-156.e4. doi: 10.1016/j.jpeds.2018.08.059. Epub 2018 Oct 3.
PubMed 30292492
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT) in Extremely Low Birth Weight Infants
- ClinicalTrials.gov ID
- NCT00233324
- Acronym / sponsor ID
- SUPPORT / NICHD-NRN-0033
- Conditions
- Infant, Newborn, Diseases, Other Preterm Infants, Infant, Small for Gestational Age, Premature Birth, Bronchopulmonary Dysplasia, Retinopathy of Prematurity
- Keywords
- NICHD Neonatal Research Network, Extremely Low Birth Weight (ELBW), Very Low Birth Weight (VLBW), Prematurity, Mechanical ventilation, Surfactant, Intubation, Neurodevelopmental impairment
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,316 participants (actual)
- Lead sponsor
- NICHD Neonatal Research NetworkResearch network
- Collaborators
- 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)
- Study start
- Feb 2005
- Primary completion
- Feb 2009 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 5 Oct 2005 (estimated)
- Results
- Posted 5 Dec 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Surfactant and Low Oxygen | Experimental | Drug: Surfactant, Drug: Supplemental oxygen with target saturation of 85 to 89%Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 85% to 89% |
| Surfactant and High Oxygen | Experimental | Drug: Surfactant, Drug: Supplemental oxygen with target saturation of 91 to 95%Administration of surfactant by endotracheal tube and supplemental oxygen with target saturationof 91% to 95% |
| CPAP and Low Oxygen | Experimental | Device: Continuous Positive Airway Pressure (CPAP), Drug: Supplemental oxygen with target saturation of 85 to 89%Administration of continuous positive airway pressure (CPAP) and supplemental oxygen with target saturation of 85% to 89% |
| CPAP and High Oxygen | Experimental | Device: Continuous Positive Airway Pressure (CPAP), Drug: Supplemental oxygen with target saturation of 91 to 95%Administration of continuous positive airway pressure (CPAP)and supplemental oxygen with target saturation of 91% to 95% |
Who may qualify
- Ages
- 24 to 27 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SurfactantIntubation and administration of surfactant by 1 hour of age. | Drug | Surfactant and High Oxygen, Surfactant and Low Oxygen |
| Continuous Positive Airway Pressure (CPAP)Also: CPAPContinuous Positive Airway Pressure/Positive End Expiratory Pressure (CPAP/PEEP) begun in the delivery room and continuing in the NICU | Device | CPAP and High Oxygen, CPAP and Low Oxygen |
| Supplemental oxygen with target saturation of 85 to 89%Also: Low oxygenSupplemental oxygen in the range of 85% to 89% until the infant is no longer requiring ventilatory support or oxygen | Drug | CPAP and Low Oxygen, Surfactant and Low Oxygen |
| Supplemental oxygen with target saturation of 91 to 95%Also: High oxygenSupplemental oxygen in the range of 91% to 95% until the infant is no longer requiring ventilatory support or oxygen. | Drug | CPAP and High Oxygen, Surfactant and High Oxygen |
Primary outcome
Survival Without Bronchopulmonary Dysplasia (BPD)
Time frame: 36 weeks
Survival Without Severe Retinopathy of Prematurity (ROP) (Threshold Disease or the Need for Surgery)
Time frame: 55 weeks
17 secondary outcomes
Death or Neurodevelopmental Impairment
Time frame: 18-22 months
Duration of Mechanical Ventilation
Time frame: Entire NICU stay, up to 120 days
Survival Without Ventilation
Time frame: From birth through first 7 days of life.
Received Surfactant Treatment
Time frame: From birth through 120 days of life.
Number of Participants With Air Leaks
Time frame: From birth through first 14 days of life.
Physiological Bronchopulmonary Dysplasia
Time frame: 36 weeks post menstrual age.
Death
Time frame: 18-22 months
Severe Intraventricular Hemorrhage (IVH)
Time frame: From birth through first 120 days of life.
Periventricular Leukomalacia (PVL)
Time frame: From birth through first 120 days of life.
Threshold Retinopathy of Prematurity (ROP) Requiring Surgery
Time frame: From birth through first 120 days of life.
Endotracheal Intubation
Time frame: Delivery Room, post-delivery
Duration of Oxygen Supplementation
Time frame: From birth through first 120 days of life.
Pulse Oximetry Values > 90%
Time frame: From birth through first 120 days of life.
Blindness in at Least One Eye
Time frame: 18-22 months
Received Postnatal Steroids
Time frame: From birth through first 120 days of life.
Necrotizing Enterocolitis (NEC)
Time frame: From birth through first 120 days of life.
Cerebral Palsy
Time frame: 18-22 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 2674614Deuticke B. Monocarboxylate transport in red blood cells: kinetics and chemical modification. Methods Enzymol. 1989;173:300-29. doi: 10.1016/s0076-6879(89)73020-2. No abstract available.
- Results publication: PubMed 20472937SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network; Carlo WA, Finer NN, Walsh MC, Rich W, Gantz MG, Laptook AR, Yoder BA, Faix RG, Das A, Poole WK, Schibler K, Newman NS, Ambalavanan N, Frantz ID 3rd, Piazza AJ, Sanchez PJ, Morris BH, Laroia N, Phelps DL, Poindexter BB, Cotten CM, Van Meurs KP, Duara S, Narendran V, Sood BG, O'Shea TM, Bell EF, Ehrenkranz RA, Watterberg KL, Higgins RD. Target ranges of oxygen saturation in extremely preterm infants. N Engl J Med. 2010 May 27;362(21):1959-69. doi: 10.1056/NEJMoa0911781. Epub 2010 May 16.
- Results publication: PubMed 20472939SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network; Finer NN, Carlo WA, Walsh MC, Rich W, Gantz MG, Laptook AR, Yoder BA, Faix RG, Das A, Poole WK, Donovan EF, Newman NS, Ambalavanan N, Frantz ID 3rd, Buchter S, Sanchez PJ, Kennedy KA, Laroia N, Poindexter BB, Cotten CM, Van Meurs KP, Duara S, Narendran V, Sood BG, O'Shea TM, Bell EF, Bhandari V, Watterberg KL, Higgins RD. Early CPAP versus surfactant in extremely preterm infants. N Engl J Med. 2010 May 27;362(21):1970-9. doi: 10.1056/NEJMoa0911783. Epub 2010 May 16.
- Results publication: PubMed 20587676Rich WD, Auten KJ, Gantz MG, Hale EC, Hensman AM, Newman NS, Finer NN; National Institute of Child Health and Human Development Neonatal Research Network. Antenatal consent in the SUPPORT trial: challenges, costs, and representative enrollment. Pediatrics. 2010 Jul;126(1):e215-21. doi: 10.1542/peds.2009-3353. Epub 2010 Jun 29.
- Results publication: PubMed 22738947Di Fiore JM, Walsh M, Wrage L, Rich W, Finer N, Carlo WA, Martin RJ; SUPPORT Study Group of Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Low oxygen saturation target range is associated with increased incidence of intermittent hypoxemia. J Pediatr. 2012 Dec;161(6):1047-52. doi: 10.1016/j.jpeds.2012.05.046. Epub 2012 Jun 26.
- Results publication: PubMed 22371462Rich W, Finer NN, Gantz MG, Newman NS, Hensman AM, Hale EC, Auten KJ, Schibler K, Faix RG, Laptook AR, Yoder BA, Das A, Shankaran S; SUPPORT and Generic Database Subcommittees of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Enrollment of extremely low birth weight infants in a clinical research study may not be representative. Pediatrics. 2012 Mar;129(3):480-4. doi: 10.1542/peds.2011-2121. Epub 2012 Feb 27.
- Results publication: PubMed 25425651Ambalavanan N, Carlo WA, Wrage LA, Das A, Laughon M, Cotten CM, Kennedy KA, Laptook AR, Shankaran S, Walsh MC, Higgins RD; SUPPORT Study Group of the NICHD Neonatal Research Network. PaCO2 in surfactant, positive pressure, and oxygenation randomised trial (SUPPORT). Arch Dis Child Fetal Neonatal Ed. 2015 Mar;100(2):F145-9. doi: 10.1136/archdischild-2014-306802. Epub 2014 Nov 25.
- Results publication: PubMed 27344218Navarrete CT, Wrage LA, Carlo WA, Walsh MC, Rich W, Gantz MG, Das A, Schibler K, Newman NS, Piazza AJ, Poindexter BB, Shankaran S, Sanchez PJ, Morris BH, Frantz ID 3rd, Van Meurs KP, Cotten CM, Ehrenkranz RA, Bell EF, Watterberg KL, Higgins RD, Duara S; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Growth Outcomes of Preterm Infants Exposed to Different Oxygen Saturation Target Ranges from Birth. J Pediatr. 2016 Sep;176:62-68.e4. doi: 10.1016/j.jpeds.2016.05.070. Epub 2016 Jun 22.
- Results publication: PubMed 24725582Stevens TP, Finer NN, Carlo WA, Szilagyi PG, Phelps DL, Walsh MC, Gantz MG, Laptook AR, Yoder BA, Faix RG, Newman JE, Das A, Do BT, Schibler K, Rich W, Newman NS, Ehrenkranz RA, Peralta-Carcelen M, Vohr BR, Wilson-Costello DE, Yolton K, Heyne RJ, Evans PW, Vaucher YE, Adams-Chapman I, McGowan EC, Bodnar A, Pappas A, Hintz SR, Acarregui MJ, Fuller J, Goldstein RF, Bauer CR, O'Shea TM, Myers GJ, Higgins RD; SUPPORT Study Group of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Respiratory outcomes of the surfactant positive pressure and oximetry randomized trial (SUPPORT). J Pediatr. 2014 Aug;165(2):240-249.e4. doi: 10.1016/j.jpeds.2014.02.054. Epub 2014 Apr 13.
- Results publication: PubMed 23268664Vaucher YE, Peralta-Carcelen M, Finer NN, Carlo WA, Gantz MG, Walsh MC, Laptook AR, Yoder BA, Faix RG, Das A, Schibler K, Rich W, Newman NS, Vohr BR, Yolton K, Heyne RJ, Wilson-Costello DE, Evans PW, Goldstein RF, Acarregui MJ, Adams-Chapman I, Pappas A, Hintz SR, Poindexter B, Dusick AM, McGowan EC, Ehrenkranz RA, Bodnar A, Bauer CR, Fuller J, O'Shea TM, Myers GJ, Higgins RD; SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network. Neurodevelopmental outcomes in the early CPAP and pulse oximetry trial. N Engl J Med. 2012 Dec 27;367(26):2495-504. doi: 10.1056/NEJMoa1208506.
- Derived from this study: PubMed 40571094Hintz SR, Bann CM, Vohr BR, McGowan EC, Vaucher YE, Fuller MG, Das A, Wilson-Costello DE, Garey DM, Sibley CK, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Neonatal Neuroimaging Among Children Born Extremely Preterm and Motor Coordination Impairment at School-Age. J Pediatr. 2025 Oct;285:114704. doi: 10.1016/j.jpeds.2025.114704. Epub 2025 Jun 24.
- Derived from this study: PubMed 37640232Lowe J, Bann CM, Dempsey AG, Fuller J, Taylor HG, Gustafson KE, Watson VE, Vohr BR, Das A, Shankaran S, Yolton K, Ball MB, Hintz SR; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Do Bayley-III Composite Scores at 18-22 Months Corrected Age Predict Full-Scale IQ at 6-7 Years in Children Born Extremely Preterm? J Pediatr. 2023 Dec;263:113700. doi: 10.1016/j.jpeds.2023.113700. Epub 2023 Aug 26.
- NICHD Neonatal Research Network siteLink provided by the sponsor.
- NICHD Pregnancy \& Perinatology BranchLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Abbot R. Laptook, MD principal investigator
Brown University, Women & Infants Hospital of Rhode Island
Michele C. Walsh, MD MS principal investigator
Case Western Reserve University, Rainbow Babies and Children's Hospital
Ronald N. Goldberg, MD principal investigator
Duke University
22 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Surfactant, Continuous Positive Airway Pressure (CPAP) and Supplemental oxygen with target saturation of 85 to 89% in people with Infant, Newborn, Diseases and Other Preterm Infants, run by NICHD Neonatal Research Network at 22 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Dec 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival Without Bronchopulmonary Dysplasia (BPD) (time frame: 36 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00233324, which also lists 19 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2019.