Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT)

NICHD Neonatal Research Network

Status and phase: Completed; Phase 3

Conditions: Retinopathy of Prematurity; Infant, Small for Gestational Age; Bronchopulmonary Dysplasia; Infant, Newborn, Diseases; Premature Birth; Other Preterm Infants

Treatments: 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%; Drug: Surfactant

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00233324

U10HD053109 (U.S. NIH Grant/Contract)

UL1RR024979 (U.S. NIH Grant/Contract)

U10HD021364 (U.S. NIH Grant/Contract)

NICHD-NRN-0033

U10HD027880 (U.S. NIH Grant/Contract)

U10HD036790 (U.S. NIH Grant/Contract)

U10HD027856 (U.S. NIH Grant/Contract)

U10HD053089 (U.S. NIH Grant/Contract)

U10HD027851 (U.S. NIH Grant/Contract)

U10HD040689 (U.S. NIH Grant/Contract)

UL1RR025008 (U.S. NIH Grant/Contract)

M01RR008084 (U.S. NIH Grant/Contract)

U10HD027871 (U.S. NIH Grant/Contract)

UL1RR024989 (U.S. NIH Grant/Contract)

UL1RR024139 (U.S. NIH Grant/Contract)

U10HD021373 (U.S. NIH Grant/Contract)

U10HD027853 (U.S. NIH Grant/Contract)

U10HD053119 (U.S. NIH Grant/Contract)

U10HD040521 (U.S. NIH Grant/Contract)

UL1RR024982 (U.S. NIH Grant/Contract)

U10HD040498 (U.S. NIH Grant/Contract)

M01RR000633 (U.S. NIH Grant/Contract)

U10HD040492 (U.S. NIH Grant/Contract)

M01RR000750 (U.S. NIH Grant/Contract)

U10HD021397 (U.S. NIH Grant/Contract)

U10HD053124 (U.S. NIH Grant/Contract)

UL1RR024128 (U.S. NIH Grant/Contract)

U10HD034216 (U.S. NIH Grant/Contract)

U10HD021385 (U.S. NIH Grant/Contract)

U10HD027904 (U.S. NIH Grant/Contract)

U10HD040461 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,316 patients

Sex: All

Ages: 24 to 27 weeks old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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1,316 participants in 4 patient groups

Surfactant and Low Oxygen

Experimental group

Description:

Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 85% to 89%

Treatment:

Drug: Surfactant

Drug: Supplemental oxygen with target saturation of 85 to 89%

Surfactant and High Oxygen

Experimental group

Description:

Administration of surfactant by endotracheal tube and supplemental oxygen with target saturationof 91% to 95%

Treatment:

Drug: Supplemental oxygen with target saturation of 91 to 95%

Drug: Surfactant

CPAP and Low Oxygen

Experimental group

Description:

Administration of continuous positive airway pressure (CPAP) and supplemental oxygen with target saturation of 85% to 89%

Treatment:

Drug: Supplemental oxygen with target saturation of 85 to 89%

Device: Continuous Positive Airway Pressure (CPAP)

CPAP and High Oxygen

Experimental group

Description:

Administration of continuous positive airway pressure (CPAP)and supplemental oxygen with target saturation of 91% to 95%

Treatment:

Drug: Supplemental oxygen with target saturation of 91 to 95%

Device: Continuous Positive Airway Pressure (CPAP)