Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT)

• Survival without bronchopulmonary dysplasia (BPD) [ Time Frame: 36 weeks ] [ Designated as safety issue: Yes ]
• Survival without severe Retinopathy of Prematurity (ROP) (threshold disease or the need for surgery) [ Time Frame: 55 weeks ] [ Designated as safety issue: Yes ]

• 1. survival without BPD at 36 weeks
• 2. survival without the occurrence of threshold ROP and/or the need for surgical intervention
• 3. Mortality/Neurodevelopmental outcome at 18-22 months corrected age

• Apgar score [ Time Frame: 5 minutes ] [ Designated as safety issue: Yes ]
• Death or neurodevelopmental impairment [ Time Frame: 18-22 months ] [ Designated as safety issue: Yes ]
• Duration of mechanical ventilation [ Time Frame: During entire NICU stay ] [ Designated as safety issue: Yes ]
• Survival without ventilation [ Time Frame: By day 7 ] [ Designated as safety issue: Yes ]
• Received surfactant treatment [ Time Frame: 120 days ] [ Designated as safety issue: Yes ]
• Incidence of air leaks [ Time Frame: 120 days ] [ Designated as safety issue: Yes ]
• Bronchopulmonary Disease (using the physiologic definition of BPD) [ Time Frame: 36 weeks ] [ Designated as safety issue: Yes ]
• Death [ Time Frame: 18-22 months ] [ Designated as safety issue: Yes ]
• Severe intraventricular hemorrhage (IVH) [ Time Frame: 120 days ] [ Designated as safety issue: Yes ]
• Periventricular leukomalacia (PVL) [ Time Frame: 120 days ] [ Designated as safety issue: Yes ]
• Threshold ROP requiring surgery [ Time Frame: 120 days ] [ Designated as safety issue: Yes ]
• Endotracheal intubation [ Time Frame: Before 10 minutes of age ] [ Designated as safety issue: Yes ]
• Duration of oxygen supplementation [ Time Frame: 120 days ] [ Designated as safety issue: Yes ]
• Pulse oximetry values > 90% [ Time Frame: 120 days ] [ Designated as safety issue: Yes ]
• Blindness in at least one eye [ Time Frame: 18-22 months ] [ Designated as safety issue: Yes ]
• Received postnatal steroids [ Time Frame: 120 days ] [ Designated as safety issue: Yes ]
• Necrotizing enterocolitis (NEC) [ Time Frame: 120 days ] [ Designated as safety issue: Yes ]
• Cerebral palsy [ Time Frame: 18-22 months ] [ Designated as safety issue: Yes ]

• endotracheal intubation before 10 minutes of age
• duration of mechanical ventilation
• surfactant treatment
• air leaks
• intubation
• duration of oxygen supplementation
• oximetry values > 90%
• blindness of at least one eye at 18-22 month
• use of postnatal steroids
• the physiologic definition of BPD
• necrotizing enterocolitis (NEC)
• IVH and severe IVH
• periventricular leukomalacia
• cerebral palsy

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.

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.

• Infant, Newborn
• Infant, Low Birth Weight
• Infant, Small for Gestational Age
• Infant, Premature
• Bronchopulmonary Dysplasia
• Retinopathy of Prematurity
• Continuous Positive Airway Pressure

• Procedure: Early surfactant
  Intubation and administration of surfactant by 1 hour of age.
• Procedure: 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
• Procedure: Target oxygen saturation of 85-89%
  SpO2 range (85% to 89%) until the infant is no longer requiring ventilatory support or oxygen.
• Procedure: Target oxygen saturation of 91-85%
  SpO2 range (91% to 95%) until the infant is no longer requiring ventilatory support or oxygen.

• Active Comparator: Surfactant and Low Oxygen
  Early Surfactant and 85-89% target oxygen saturation
  Interventions:

  • Procedure: Early surfactant
  • Procedure: Target oxygen saturation of 85-89%
• Active Comparator: Surfactant and High Oxygen
  Early Surfactant and 91-95% target oxygen saturation
  Interventions:

  • Procedure: Early surfactant
  • Procedure: Target oxygen saturation of 91-85%
• Active Comparator: CPAP and Low Oxygen
  CPAP and 85-89% target oxygen saturation
  Interventions:

  • Procedure: Continuous Positive Airway Pressure (CPAP)
  • Procedure: Target oxygen saturation of 85-89%
• Active Comparator: CPAP and High Oxygen
  CPAP and 91-95% target oxygen saturation
  Interventions:

  • Procedure: Continuous Positive Airway Pressure (CPAP)
  • Procedure: Target oxygen saturation of 91-85%

• 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, Sánchez 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. Epub 2010 May 16.
• 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, Sánchez 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. Epub 2010 May 16.
• 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. Epub 2010 Jun 29.
• Di Fiore JM, Walsh M, Wrage L, Rich W, Finer N, Carlo WA, Martin RJ; SUPPORT Study Group of the 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):1047-1052.e1. doi: 10.1016/j.jpeds.2012.05.046. Epub 2012 Jun 26.
• 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. Epub 2012 Feb 27.
• 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.

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

• National Heart, Lung, and Blood Institute (NHLBI)
• National Center for Research Resources (NCRR)