Clinical trial NCT00233324: Surfactant Positive Airway Pressure and Pulse Oximetry Trial
Official title: Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT) in Extremely Low Birth Weight Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
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
Pulse oximetry
Oxygen saturation
Positive-Pressure Respiration
Lead sponsor: NICHD Neonatal Research Network
Sponsor class: NETWORK
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: National Center for Research Resources (NCRR)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2005-10-05
Enrollment: 1316
Sex: ALL
Minimum age (years): 24
Maximum age (years): 27
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Survival Without Bronchopulmonary Dysplasia (BPD)
timeFrame: 36 weeks
measure: Survival Without Severe Retinopathy of Prematurity (ROP) (Threshold Disease or the Need for Surgery)
timeFrame: 55 weeks
Secondary outcomes:
measure: Death or Neurodevelopmental Impairment
timeFrame: 18-22 months
measure: Duration of Mechanical Ventilation
timeFrame: Entire NICU stay, up to 120 days
measure: Survival Without Ventilation
timeFrame: From birth through first 7 days of life.
measure: Received Surfactant Treatment
timeFrame: From birth through 120 days of life.
measure: Number of Participants With Air Leaks
timeFrame: From birth through first 14 days of life.
measure: Physiological Bronchopulmonary Dysplasia
timeFrame: 36 weeks post menstrual age.
measure: Death
timeFrame: 18-22 months
measure: Severe Intraventricular Hemorrhage (IVH)
timeFrame: From birth through first 120 days of life.
measure: Periventricular Leukomalacia (PVL)
timeFrame: From birth through first 120 days of life.
measure: Threshold Retinopathy of Prematurity (ROP) Requiring Surgery
timeFrame: From birth through first 120 days of life.
measure: Endotracheal Intubation
timeFrame: Delivery Room, post-delivery
measure: Duration of Oxygen Supplementation
timeFrame: From birth through first 120 days of life.
measure: Pulse Oximetry Values > 90%
timeFrame: From birth through first 120 days of life.
measure: Blindness in at Least One Eye
timeFrame: 18-22 months
measure: Received Postnatal Steroids
timeFrame: From birth through first 120 days of life.
measure: Necrotizing Enterocolitis (NEC)
timeFrame: From birth through first 120 days of life.
measure: Cerebral Palsy
timeFrame: 18-22 months
Other outcomes:
measure: Apgar Scores at 5 Minutes
timeFrame: 5 minutes after birth.
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: San Diego
country: United States
facility: University of California at San Diego
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Charlotte
country: United States
facility: Wake Forest University
state: North Carolina
city: Durham
country: United States
facility: RTI International
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve University, Rainbow Babies and Children's Hospital
state: Ohio
city: Providence
country: United States
facility: Brown University, Women & Infants Hospital of Rhode Island
state: Rhode Island
city: Memphis
country: United States
facility: University of Tennessee
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center at Dallas
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: Brown University, Women & Infants Hospital of Rhode Island
name: Abbot R. Laptook, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Case Western Reserve University, Rainbow Babies and Children's Hospital
name: Michele C. Walsh, MD MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Ronald N. Goldberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Emory University
name: Barbara J. Stoll, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Indiana University
name: Brenda B. Poindexter, MD MS
role: PRINCIPAL_INVESTIGATOR
affiliation: RTI International
name: Abhik Das, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Krisa P. Van Meurs, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tufts Medical Center
name: Ivan D. Frantz III, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Diego
name: Neil N. Finer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital Medical Center, Cincinnati
name: Kurt Schibler, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alabama at Birmingham
name: Waldemar A. Carlo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Iowa
name: Edward F. Bell, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of New Mexico
name: Kristi L. Watterberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas, Southwestern Medical Center at Dallas
name: Pablo J. Sanchez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The University of Texas Health Science Center, Houston
name: Kathleen A. Kennedy, MD MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Utah
name: Roger G. Faix, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wayne State University
name: Seetha Shankaran, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale University
name: Richard A. Ehrenkranz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: SUPPORT 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.
citation: SUPPORT 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.
citation: Rich 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.
citation: Di 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.
citation: Rich 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.
citation: Ambalavanan 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.
citation: Navarrete 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.
citation: Stevens 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.
citation: Vaucher 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.
citation: Lowe 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.
citation: Duncan 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.
citation: Duncan 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.
citation: Chawla S, Natarajan G, Shankaran S, Carper B, Brion LP, Keszler M, Carlo WA, Ambalavanan N, Gantz MG, Das A, Finer N, Goldberg RN, Cotten CM, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Markers of Successful Extubation in Extremely Preterm Infants, and Morbidity After Failed Extubation. J Pediatr. 2017 Oct;189:113-119.e2. doi: 10.1016/j.jpeds.2017.04.050. Epub 2017 Jun 7.
citation: Di Fiore JM, Martin RJ, Li H, Morris N, Carlo WA, Finer N, Walsh M; SUPPORT Study Group of the Eunice Kennedy Shriver National Institute of Child Health, and Human Development Neonatal Research Network. Patterns of Oxygenation, Mortality, and Growth Status in the Surfactant Positive Pressure and Oxygen Trial Cohort. J Pediatr. 2017 Jul;186:49-56.e1. doi: 10.1016/j.jpeds.2017.01.057. Epub 2017 Mar 6.
citation: Hintz SR, Barnes PD, Bulas D, Slovis TL, Finer NN, Wrage LA, Das A, Tyson JE, Stevenson DK, Carlo WA, Walsh MC, Laptook AR, Yoder BA, Van Meurs KP, Faix RG, Rich W, Newman NS, Cheng H, Heyne RJ, Vohr BR, Acarregui MJ, Vaucher YE, Pappas A, Peralta-Carcelen M, Wilson-Costello DE, Evans PW, Goldstein RF, Myers GJ, Poindexter BB, McGowan EC, Adams-Chapman I, Fuller J, Higgins RD; SUPPORT Study Group of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Neuroimaging and neurodevelopmental outcome in extremely preterm infants. Pediatrics. 2015 Jan;135(1):e32-42. doi: 10.1542/peds.2014-0898. Epub 2014 Dec 1.
citation: LeVan JM, Brion LP, Wrage LA, Gantz MG, Wyckoff MH, Sanchez PJ, Heyne R, Jaleel M, Finer NN, Carlo WA, Das A, Stoll BJ, Higgins RD; Eunice Kennedy Shriver NICHD Neonatal Research Network. Change in practice after the Surfactant, Positive Pressure and Oxygenation Randomised Trial. Arch Dis Child Fetal Neonatal Ed. 2014 Sep;99(5):F386-90. doi: 10.1136/archdischild-2014-306057. Epub 2014 May 29.