Surfactant Positive Airway Pressure and Pulse Oximetry Trial
Condition: Infant, Newborn, Diseases; Other Preterm Infants; Infant, Small for Gestational Age; Premature Birth; Bronchopulmonary Dysplasia; Retinopathy of Prematurity
MeSH terms: Bronchopulmonary Dysplasia; Retinopathy of Prematurity; Premature Birth; Infant, Newborn, Diseases; Birth Weight
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): Surfactant; Continuous Positive Airway Pressure (CPAP); Supplemental oxygen with target saturation of 85 to 89%; Supplemental oxygen with target saturation of 91 to 95%
Intervention type(s): Drug; Device; Drug; Drug
Intervention description(s): Intubation and administration of surfactant by 1 hour of age.; Continuous Positive Airway Pressure/Positive End Expiratory Pressure (CPAP/PEEP) begun in the delivery room and continuing in the NICU; Supplemental oxygen in the range of 85% to 89% until the infant is no longer requiring ventilatory support or oxygen; Supplemental oxygen in the range of 91% to 95% until the infant is no longer requiring ventilatory support or oxygen.
Other intervention name(s): CPAP; Low oxygen; High oxygen
Intervention MeSH terms: Pulmonary Surfactants
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Primary purpose: Treatment
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