Surfactant Positive Airway Pressure and Pulse Oximetry Trial

Study Overview
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Brief Summary
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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
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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.

Official Title
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Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT) in Extremely Low Birth Weight Infants

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

Intervention / Treatment
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* Drug: Surfactant
* 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%


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 24 Weeks
Maximum Age: 27 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Surfactant and Low Oxygen<br>Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 85% to 89% | Drug: Surfactant<br>* Intubation and administration of surfactant by 1 hour of age.<br>Drug: Supplemental oxygen with target saturation of 85 to 89%<br>* Supplemental oxygen in the range of 85% to 89% until the infant is no longer requiring ventilatory support or oxygen<br>* Other names: Low oxygen;|
| Experimental: Surfactant and High Oxygen<br>Administration of surfactant by endotracheal tube and supplemental oxygen with target saturationof 91% to 95% | Drug: Surfactant<br>* Intubation and administration of surfactant by 1 hour of age.<br>Drug: Supplemental oxygen with target saturation of 91 to 95%<br>* Supplemental oxygen in the range of 91% to 95% until the infant is no longer requiring ventilatory support or oxygen.<br>* Other names: High oxygen;|
| Experimental: CPAP and Low Oxygen<br>Administration of continuous positive airway pressure (CPAP) and supplemental oxygen with target saturation of 85% to 89% | Device: Continuous Positive Airway Pressure (CPAP)<br>* Continuous Positive Airway Pressure/Positive End Expiratory Pressure (CPAP/PEEP) begun in the delivery room and continuing in the NICU<br>* Other names: CPAP;Drug: Supplemental oxygen with target saturation of 85 to 89%<br>* Supplemental oxygen in the range of 85% to 89% until the infant is no longer requiring ventilatory support or oxygen<br>* Other names: Low oxygen;|
| Experimental: CPAP and High Oxygen<br>Administration of continuous positive airway pressure (CPAP)and supplemental oxygen with target saturation of 91% to 95% | Device: Continuous Positive Airway Pressure (CPAP)<br>* Continuous Positive Airway Pressure/Positive End Expiratory Pressure (CPAP/PEEP) begun in the delivery room and continuing in the NICU<br>* Other names: CPAP;Drug: Supplemental oxygen with target saturation of 91 to 95%<br>* Supplemental oxygen in the range of 91% to 95% until the infant is no longer requiring ventilatory support or oxygen.<br>* Other names: High oxygen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival Without Bronchopulmonary Dysplasia (BPD) |  | 36 weeks | 
| Survival Without Severe Retinopathy of Prematurity (ROP) (Threshold Disease or the Need for Surgery) |  | 55 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death or Neurodevelopmental Impairment |  | 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. | 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 | From birth through first 7 days of life. | 
| Received Surfactant Treatment | Received any surfactant treatment. | 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. | 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. | 36 weeks post menstrual age. | 
| Death | Participants who died by their follow-up visit at 18-22 months. | 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. | From birth through first 120 days of life. | 
| Periventricular Leukomalacia (PVL) | Increased echogenicity or cysts in periventricular region. | 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. | From birth through first 120 days of life. | 
| Endotracheal Intubation | Insertion of a tube into the trachea to allow positive pressure ventilation for breathing. | Delivery Room, post-delivery | 
| Duration of Oxygen Supplementation | The length of time in days that a participant had oxygen supplementation. | From birth through first 120 days of life. | 
| Pulse Oximetry Values > 90% | Percentage of time spent above 90% oxygen saturation. | 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. | 18-22 months | 
| Received Postnatal Steroids | Participant received any doses or courses of systemic steroids to prevent or treat bronchopulmonary dysplasia/chronic lung disease. | 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. | From birth through first 120 days of life. | 
| Cerebral Palsy | Incidence of cerebral palsy. | 18-22 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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