Delivery Room Management Trial of Premature Infants at High Risk of Respiratory Distress Syndrome

Study Overview
=================
Brief Summary
-----------------
The best mode of delivery room stabilization for premature infants at high risk for respiratory distress syndrome is unknown. The protocol evaluates the impact of three distinct methods of post-delivery stabilization and subsequent early respiratory care on chronic lung disease and survival in premature infants at high risk for respiratory distress syndrome.

Detailed Description
-----------------
The Delivery room management of premature infants at high risk of respiratory distress syndrome protocol compares three distinct methods of post-delivery stabilization and subsequent early respiratory care on chronic lung disease and survival in premature infants at high risk of respiratory distress syndrome. The three approaches to post-delivery care include: Intubation, prophylactic surfactant administration shortly after delivery, and subsequent stabilization on ventilator support. Early stabilization on nasal continuous positive airway pressure (NCPAP) with selective intubation and surfactant administration for clinical indications. Intubation, prophylactic surfactant administration shortly after delivery and rapid extubation to nasal CPAP. The primary null hypothesis for this study is that no difference will be found in chronic lung disease and/or mortality at 36 weeks adjusted age in premature infants at high risk of RDS, depending on the method of post-delivery stabilization. The study is a randomized, multicenter trial conducted at participating Vermont Oxford Network Centers. Participating centers will demonstrate competency in the use of nasal CPAP by successfully completing a web-based, educational program and utilizing nasal CPAP in a minimum of 20 infants in their NICU. Infants likely to be delivered to women presenting to a participating Vermont Oxford Network Center at high risk of premature delivery at gestational age 26 + 0 to 29 + 6 weeks will be eligible for inclusion. Specific inclusion criteria that must be met prior to randomization include: imminent delivery no potentially life-threatening congenital anomaly or genetic syndrome no known lung maturity antenatal steroid status known written and informed consent obtained prior to delivery. Exclusion criteria will include: stillborn infants (Apgar score of 0 at one minute of age) or infants noted to have a potentially life-threatening congenital anomaly or genetic syndrome noted immediately after delivery. Eligible infants will have consent obtained prior to delivery. They will be stratified into two groups: 26 + 0 to 27 + 6 weeks gestation and 28 + 0 to 29 + 6 weeks gestation. Shortly before delivery, infants will be randomized to one of the three stabilization strategies detailed below: Intubation, prophylactic surfactant administration shortly after delivery, and subsequent stabilization on ventilator support (PS group). Early stabilization on nasal continuous positive airway pressure (NCPAP) with selected intubation and surfactant administration for clinical indications (NCPAP group). Intubation, prophylactic surfactant administration shortly after delivery, and rapid extubation to nasal CPAP (ISX group). Infants requiring intubation for respiratory failure during this study (in any of the three groups) may be stabilized on either conventional or high-frequency ventilation. Specific criteria regarding target ranges for blood gases and indications for extubation, subsequent surfactant dosing, management of extubation, and criteria for reintubation, are all detailed in the protocol. The primary outcome measure is chronic lung disease (defined as documented requirement for supplemental oxygen or respiratory support) or mortality at 36 weeks adjusted age. Secondary outcome measures include a variety of clinical outcomes, as well as issues regarding duration of hospital stay and other resource utilization. Long-term outcomes will be measured by a health care questionnaire at two years of age. A sample size of over 895 infants will be required to demonstrate a 25% reduction in the risk of chronic lung disease at 36 weeks adjusted age.

Official Title
-----------------
Delivery Room Management of Premature Infants at High Risk of Respiratory Distress Syndrome

Conditions
-----------------
Respiratory Distress Syndrome, Newborn

Intervention / Treatment
-----------------
* Drug: PS Group
* Device: NCPAP Group
* Drug: ISX Group


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Infants likely to be delivered to women presenting to a participating Vermont Oxford Network Center at high risk of premature delivery at gestational age 26 + 0 to 29 + 6 weeks will be eligible for inclusion. Specific inclusion criteria that must be met prior to randomization include: Imminent delivery No potentially life-threatening congenital anomaly or genetic syndrome No known lung maturity Antenatal steroid status known Written, informed consent obtained (on admission or prior to delivery). Exclusion Criteria: Stillborn (Apgar score of 0 at one minute of age) Noted to have a potentially life-threatening congenital anomaly or genetic syndrome noted immediately after delivery.

Ages Eligible for Study
-----------------
Minimum Age: 26 Weeks
Maximum Age: 29 Weeks

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PS Group<br>Intubation, prophylactic surfactant administration shortly after delivery, and subsequent stabilization on ventilator support. | Drug: PS Group<br>* Intubation, prophylactic surfactant administration shortly after delivery, and subsequent stabilization on ventilator support.<br>* Other names: Prophylactic Surfactant Group;|
| Experimental: NCPAP Group<br>Early stabilization on nasal continuous positive airway pressure (NCPAP) with selected intubation and surfactant administration for clinical indications. | Device: NCPAP Group<br>* Early stabilization on nasal continuous positive airway pressure (NCPAP) with selected intubation and surfactant administration for clinical indications.<br>* Other names: Nasal CPAP group;|
| Experimental: ISX Group<br>Intubation, prophylactic surfactant administration shortly after delivery, and rapid extubation to nasal CPAP. | Drug: ISX Group<br>* Intubation, prophylactic surfactant administration shortly after delivery, and rapid extubation to nasal CPAP.<br>* Other names: Intubation, Surfactant Administration, Extubation to Nasal CPAP. ENSURE.;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death or Chronic Lung Disease |  | at 36 weeks postmenstrual age | 
| Death |  | 36 weeks adjusted age | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Prematurity, respiratory distress syndrome, surfactant, nasal continuous positive airway pressure