Surfactant Positive Airway Pressure and Pulse Oximetry Trial
- Conditions
- Other Preterm InfantsInfant, Small for Gestational AgePremature BirthRetinopathy of PrematurityInfant, Newborn, DiseasesBronchopulmonary Dysplasia
- Interventions
- Drug: SurfactantDevice: Continuous Positive Airway Pressure (CPAP)Drug: Supplemental oxygen with target saturation of 91 to 95%Drug: Supplemental oxygen with target saturation of 85 to 89%
- Registration Number
- NCT00233324
- Lead Sponsor
- NICHD Neonatal Research Network
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1316
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Surfactant and High Oxygen Surfactant Administration of surfactant by endotracheal tube and supplemental oxygen with target saturationof 91% to 95% Surfactant and High Oxygen Supplemental oxygen with target saturation of 91 to 95% Administration of surfactant by endotracheal tube and supplemental oxygen with target saturationof 91% to 95% CPAP and Low Oxygen Continuous Positive Airway Pressure (CPAP) Administration of continuous positive airway pressure (CPAP) and supplemental oxygen with target saturation of 85% to 89% Surfactant and Low Oxygen Supplemental oxygen with target saturation of 85 to 89% Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 85% to 89% CPAP and High Oxygen Continuous Positive Airway Pressure (CPAP) Administration of continuous positive airway pressure (CPAP)and supplemental oxygen with target saturation of 91% to 95% Surfactant and Low Oxygen Surfactant Administration of surfactant by endotracheal tube and supplemental oxygen with target saturation of 85% to 89% CPAP and Low Oxygen Supplemental oxygen with target saturation of 85 to 89% Administration of continuous positive airway pressure (CPAP) and supplemental oxygen with target saturation of 85% to 89% CPAP and High Oxygen Supplemental oxygen with target saturation of 91 to 95% Administration of continuous positive airway pressure (CPAP)and supplemental oxygen with target saturation of 91% to 95%
- Primary Outcome Measures
Name Time Method 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
Name Time Method Death 18-22 months Participants who died by their follow-up visit at 18-22 months.
Periventricular Leukomalacia (PVL) From birth through first 120 days of life. Increased echogenicity or cysts in periventricular region.
Threshold Retinopathy of Prematurity (ROP) Requiring Surgery From birth through first 120 days of life. Diagnosis of retinopathy of prematurity which resulted in requiring surgery.
Death or Neurodevelopmental Impairment 18-22 months Duration of Mechanical Ventilation Entire NICU stay, up to 120 days The length in days that an individual was on mechanical ventilation which includes high frequency and conventional ventilation.
Survival Without Ventilation From birth through first 7 days of life. Surviving the first 7 days of life without any need for ventilation by day 7
Received Surfactant Treatment From birth through 120 days of life. Received any surfactant treatment.
Number of Participants With Air Leaks From birth through first 14 days of life. Number of participants with air leaks including pnemothorax, pulmonary interstitial emphysema (PIE), and pneumopericardium.
Physiological Bronchopulmonary Dysplasia 36 weeks post menstrual age. 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.
Severe Intraventricular Hemorrhage (IVH) From birth through first 120 days of life. 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.
Endotracheal Intubation Delivery Room, post-delivery Insertion of a tube into the trachea to allow positive pressure ventilation for breathing.
Duration of Oxygen Supplementation From birth through first 120 days of life. The length of time in days that a participant had oxygen supplementation.
Pulse Oximetry Values > 90% From birth through first 120 days of life. Percentage of time spent above 90% oxygen saturation.
Blindness in at Least One Eye 18-22 months Blindness in at least one eye by 18-22 months of life.
Received Postnatal Steroids From birth through first 120 days of life. Participant received any doses or courses of systemic steroids to prevent or treat bronchopulmonary dysplasia/chronic lung disease.
Necrotizing Enterocolitis (NEC) From birth through first 120 days of life. Proven necrotizing enterocolitis (NEC) diagnosis using the Modified Bell's Staging Criteria for NEC.
Cerebral Palsy 18-22 months Incidence of cerebral palsy.
Trial Locations
- Locations (22)
University of California at San Diego
🇺🇸San Diego, California, United States
University of Miami
🇺🇸Miami, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Case Western Reserve University, Rainbow Babies and Children's Hospital
🇺🇸Cleveland, Ohio, United States
University of Texas Health Science Center at Houston
🇺🇸Houston, Texas, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Wayne State University
🇺🇸Detroit, Michigan, United States
Yale University
🇺🇸New Haven, Connecticut, United States
University of Rochester
🇺🇸Rochester, New York, United States
University of New Mexico
🇺🇸Albuquerque, New Mexico, United States
Cincinnati Children's Medical Center
🇺🇸Cincinnati, Ohio, United States
Duke University
🇺🇸Durham, North Carolina, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Wake Forest University
🇺🇸Charlotte, North Carolina, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
RTI International
🇺🇸Durham, North Carolina, United States
Brown University, Women & Infants Hospital of Rhode Island
🇺🇸Providence, Rhode Island, United States
University of Tennessee
🇺🇸Memphis, Tennessee, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
University of Texas Southwestern Medical Center at Dallas
🇺🇸Dallas, Texas, United States
Stanford University
🇺🇸Palo Alto, California, United States