Sustained Aeration of Infant Lungs Trial

Study Overview
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Brief Summary
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This study is a 2-arm randomized, controlled, multi-center clinical trial to determine which of two strategies at birth are best to optimally aerate the lung of preterm infants. Specifically we will determine in 600 infants of 23-26 weeks gestational age (GA) requiring respiratory support at birth which of two lung opening strategies - either a standard PEEP/CPAP of 5-7 cm H2O in the delivery room (DR), as compared to early lung recruitment using Sustained Inflation (SI) in the DR, will result in a lower rate of the combined endpoint of death or bronchopulmonary dysplasia (BPD) at 36 weeks gestational age. Hypotheses: Early lung recruitment with SI superimposed upon standard PEEP/CPAP in the DR will reduce the need for mechanical ventilation in the first seven days of life, and reduce need for surfactant use; and A policy of DR SI on standard PEEP/CPAP recruitment will confer better outcomes at 36 weeks post-menstrual age (PMA) than standard PEEP/CPAP

Detailed Description
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The SAIL trial aims to provide evidence for changing policy or standard of care. The context of this trial is an unacceptable rate of poor long-term outcomes of preterm infants born as Extremely Low Gestational Age Newborns (ELGAN) <1000 g birthweight (BW), but especially for those born between 23-26 weeks' gestational age (GA). Such infants are the most vulnerable and immature in all organ systems, including the lungs and the brain. These infants are at high risk of death and bronchopulmonary dysplasia (BPD) during their initial hospitalization, neurodevelopmental impairment (NDI) and pulmonary problems in infancy and childhood. The SAIL trial focuses on facilitating the difficult transition of these most vulnerable infants from a liquid filled in-utero lung to an ex-utero air-filled lung. Sustained Inflation (SI) is a promising delivery room (DR) intervention, with evidence of short-term efficacy with minimal risk of additional harm beyond current standard accepted Newborn Resuscitation Program (NRP) Guidelines. This protocol proposes a fully informed consenting procedure. We propose to evaluate the impact of a SI in the DR on the need for mechanical ventilation in the first week of life which would also impact mortality rates and the incidence and severity of BPD.

Official Title
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Sustained Aeration of Infant Lungs Trial

Conditions
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Preterm Birth, Extreme Prematurity

Intervention / Treatment
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* Procedure: Sustained Inflation
* Procedure: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Gestational age (GA) at least 23 weeks but less than 27 completed weeks by best obstetrical estimate Requiring resuscitation/respiratory intervention at birth -apneic, labored breathing, gasping (as defined in NRP 2011 AAP 6th Edition p.45) Exclusion Criteria: Considered non-viable by the attending neonatologist Refusal of antenatal informed consent Known major anomalies, pulmonary hypoplasia Mothers who are unable to consent for their medical care and who do not have a surrogate guardian will not be approached for consent

Ages Eligible for Study
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Minimum Age: 23 Weeks
Maximum Age: 26 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control Arm-Standard of care<br>Control Arm-Respiratory support using Standard of Care positive-end expiratory pressure/continuous positive airway pressure (PEEP/CPAP) of 5-7 cm H2O compared to Sustained Inflation intervention | Procedure: Standard of Care<br>* Newborn Resuscitation Program (NRP) Guidelines using a standard PEEP/CPAP of 5-7 cm H2O as compared to the Sustained Inflation intervention<br>|
| Experimental: Sustained Intervention<br>Administer delivery room respiratory support using a Sustained Inflation (SI) intervention and expiratory pressure/continuous positive airway pressure (PEEP/CPAP) of 5-7 cm H2O | Procedure: Sustained Inflation<br>* The first sustained inflation will use inflation pressure of 20 cm H20 for 15 seconds<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined Outcome of Death or Bronchopulmonary Dysplasia | To determine in infants born at 23-26 weeks gestational age requiring respiratory support at birth, which of two treatment strategies when compared, results in a lower rate of the combined endpoint of death or bronchopulmonary dysplasia. | 36 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxygen Profile Over First 24 Hours | Oxygen profile over first 24 hours post delivery room using hourly FiO2 records | First 24 hours post delivery | 
| Oxygen Profile With Highest FiO2 Level up to 48 Hours | Highest FiO2 level recorded during the first 48 hours post DR | 48 hours of life | 
| Heart Rate in the Delivery Room (DR) | Categorical variable with 3 levels: <60, 60-100, >100 | First 30 seconds of life in DR | 
| Detailed Status on Departure From the Delivery Room (DR) | Type of respiratory support (CPAP, PPV) and Fraction of Inspired Oxygen (FiO2) on departure from DR | Resuscitation time will vary - 1 to 30 minutes | 
| Use of Inotropes on Arrival in NICU | Circulatory support post-delivery room | First 48 hours of life | 
| Need for Intubation in Delivery Room | Need for intubation in delivery room during the first 30 seconds to 24 hours of age | First 30 seconds to 24 hours of life | 
| Pressure-volume Characteristics in the Delivery Room (DR) | Pressure-volume characteristics in the Delivery room (DR) expected within 30 minutes | Expected average 30 minutes | 
| Pneumothorax or New Chest Drains in the First 48 Hours of Life | Chest x-ray reports showing pneumothorax or new chest drains in the first 48 hours of life | First 48 hours of life | 
| Duration of Any Chest Drain In-situ Post-DR | Duration of any chest drain in-situ post-DR during hospitalization - up to 36 weeks Post Menstrual Age (PMA) | During hospitalization - up to 36 weeks Post Menstrual Age (PMA) | 
| Intraventricular Hemorrhage by All Grades | Head ultrasound and/or MRI findings of intraventricular hemorrhage by all grades focusing on grades 3 and 4 by 48 hour and by day 10 | 48 hours to 10 days | 
| Chest X-ray Between Days 7-10 | Chest x-ray between the first 7-10 days of life | First 7-10 days of life | 
| Death or Need for Positive Pressure Ventilation | Death or need for positive pressure ventilation during the first 7 days of life | First 7 days of life | 
| Highest FiO2 and Area Under the FiO2 Curve for the First Week of Life | Highest FiO2 and Area under the FiO2 curve during the first 7 days of life | First 7 days of life | 
| Pneumothorax and Pulmonary Interstitial Emphysema (PIE) | Pneumothorax and pulmonary interstitial emphysema (PIE) during the first 10 days of life | First 10 days of life | 
| Survival to Discharge Home Without BPD, Retinopathy of Prematurity (Grades 3 & 4), or Significant Brain Abnormalities on Head Ultrasound | Survival to discharge home without BPD, retinopathy of prematurity (grades 3 & 4), or significant brain abnormalities on head ultrasound with an expected discharge between 36-40 weeks PMA | Expected discharge between 36 - 40 weeks PMA | 
| Duration of Respiratory Support (Ventilation, CPAP, Supplemental Oxygen) | Duration of respiratory support (ventilation, CPAP, supplemental oxygen) during hospitalization upto 36 weeks Post Menstrual Age (PMA) | During hospitalization - up to 36 weeks Post Menstrual Age (PMA) | 
| Death in Hospital | Death in hospital during expected hospitalization of 23-40 weeks PMA | During expected hospitalization 23 - 40 weeks PMA | 
| Retinopathy of Prematurity (ROP) Stage 3 or Greater Requiring Treatment | Retinopathy of prematurity (ROP) stage 3 or greater requiring treatment at 36 weeks | 36 weeks | 
| Use of Postnatal Steroids for Treatment of BPD | Use of postnatal steroids for treatment of BPD during hospitalization up to 36 weeks Post Menstrual Age (PMA) | During hospitalization - up to 36 weeks Post Menstrual Age (PMA) | 
| Length of Hospital Stay | Length of hospital stay with average discharge between 36-40 weeks PMA | Average discharge between 36 - 40 weeks PMA | 
| Neurodevelopmental and Respiratory Outcome at 22-26 Months Corrected Gestational Age | Neurodevelopmental and respiratory outcome at 22-26 months corrected gestational age | 22-26 months corrected gestational age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neonatal resuscitation, Extreme Low Gestational Age Newborn (ELGAN), Delivery Room, Continuous positive airway pressure (CPAP), Positive pressure ventilation (PPV), Sustained inflation