Surfactant Positive Airway Pressure and Pulse Oximetry Trial

Premature Birth Clinical Trial

— SUPPORT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00233324
• Other study ID #: NICHD-NRN-0033
• Secondary ID: U10HD021364U10HD
• Status: Completed
• Phase: Phase 3
• Start date: February 2005
• Est. completion date: August 2016

Study information

• Verified date: April 2019
• Source: NICHD Neonatal Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 1316
• Est. completion date: August 2016
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 24 Weeks to 27 Weeks

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Surfactant
Intubation and administration of surfactant by 1 hour of age.

Device:
• 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

Drug:
• Supplemental oxygen with target saturation of 85 to 89%
Supplemental oxygen in the range of 85% to 89% until the infant is no longer requiring ventilatory support or oxygen
• Supplemental oxygen with target saturation of 91 to 95%
Supplemental oxygen in the range of 91% to 95% until the infant is no longer requiring ventilatory support or oxygen.

Locations

Country	Name	City	State
United States	University of New Mexico	Albuquerque	New Mexico
United States	Emory University	Atlanta	Georgia
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Tufts Medical Center	Boston	Massachusetts
United States	Wake Forest University	Charlotte	North Carolina
United States	Cincinnati Children's Medical Center	Cincinnati	Ohio
United States	Case Western Reserve University, Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas
United States	Wayne State University	Detroit	Michigan
United States	Duke University	Durham	North Carolina
United States	RTI International	Durham	North Carolina
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of Iowa	Iowa City	Iowa
United States	University of Tennessee	Memphis	Tennessee
United States	University of Miami	Miami	Florida
United States	Yale University	New Haven	Connecticut
United States	Stanford University	Palo Alto	California
United States	Brown University, Women & Infants Hospital of Rhode Island	Providence	Rhode Island
United States	University of Rochester	Rochester	New York
United States	University of Utah	Salt Lake City	Utah
United States	University of California at San Diego	San Diego	California

Sponsors (4)

Lead Sponsor	Collaborator
NICHD Neonatal Research Network	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Center for Research Resources (NCRR), National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (10)

Ambalavanan N, Carlo WA, Wrage LA, Das A, Laughon M, Cotten CM, Kennedy KA, Laptook AR, Shankaran S, Walsh MC, Higgins RD; SUPPORT Study Group of the NICHD Neonatal Research Network. PaCO2 in surfactant, positive pressure, and oxygenation randomised trial — View Citation

Deuticke B. Monocarboxylate transport in red blood cells: kinetics and chemical modification. Methods Enzymol. 1989;173:300-29. — View Citation

Di Fiore JM, Walsh M, Wrage L, Rich W, Finer N, Carlo WA, Martin RJ; SUPPORT Study Group of Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Low oxygen saturation target range is associated with in — View Citation

Navarrete CT, Wrage LA, Carlo WA, Walsh MC, Rich W, Gantz MG, Das A, Schibler K, Newman NS, Piazza AJ, Poindexter BB, Shankaran S, Sánchez PJ, Morris BH, Frantz ID 3rd, Van Meurs KP, Cotten CM, Ehrenkranz RA, Bell EF, Watterberg KL, Higgins RD, Duara S; E — View Citation

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 Deve — View Citation

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 — View Citation

Stevens TP, Finer NN, Carlo WA, Szilagyi PG, Phelps DL, Walsh MC, Gantz MG, Laptook AR, Yoder BA, Faix RG, Newman JE, Das A, Do BT, Schibler K, Rich W, Newman NS, Ehrenkranz RA, Peralta-Carcelen M, Vohr BR, Wilson-Costello DE, Yolton K, Heyne RJ, Evans PW — View Citation

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, — View Citation

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, — View Citation

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, — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Apgar Scores at 5 Minutes	Apgar stands for "Appearance, Pulse, Grimace, Activity, and Respiration" and scores range from 1 (worst) to 10 (best) indicating a baby's condition 5 minutes after birth.	5 minutes after birth.
Primary	Survival Without Bronchopulmonary Dysplasia (BPD)		36 weeks
Primary	Survival Without Severe Retinopathy of Prematurity (ROP) (Threshold Disease or the Need for Surgery)		55 weeks
Secondary	Death or Neurodevelopmental Impairment		18-22 months
Secondary	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
Secondary	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.
Secondary	Received Surfactant Treatment	Received any surfactant treatment.	From birth through 120 days of life.
Secondary	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.
Secondary	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.
Secondary	Death	Participants who died by their follow-up visit at 18-22 months.	18-22 months
Secondary	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.
Secondary	Periventricular Leukomalacia (PVL)	Increased echogenicity or cysts in periventricular region.	From birth through first 120 days of life.
Secondary	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.
Secondary	Endotracheal Intubation	Insertion of a tube into the trachea to allow positive pressure ventilation for breathing.	Delivery Room, post-delivery
Secondary	Duration of Oxygen Supplementation	The length of time in days that a participant had oxygen supplementation.	From birth through first 120 days of life.
Secondary	Pulse Oximetry Values > 90%	Percentage of time spent above 90% oxygen saturation.	From birth through first 120 days of life.
Secondary	Blindness in at Least One Eye	Blindness in at least one eye by 18-22 months of life.	18-22 months
Secondary	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.
Secondary	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.
Secondary	Cerebral Palsy	Incidence of cerebral palsy.	18-22 months

External Links

•   NICHD Neonatal Research Network site
•   NICHD Pregnancy & Perinatology Branch