Sustained Aeration of Infant Lungs Trial
- Conditions
- Preterm BirthExtreme Prematurity
- Interventions
- Procedure: Standard of CareProcedure: Sustained Inflation
- Registration Number
- NCT02139800
- Lead Sponsor
- University of Pennsylvania
- Brief Summary
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:
1. 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
2. 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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 460
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Control Arm-Standard of care Standard of Care 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 Sustained Intervention Sustained Inflation 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
- Primary Outcome Measures
Name Time Method Combined Outcome of Death or Bronchopulmonary Dysplasia 36 weeks 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.
- Secondary Outcome Measures
Name Time Method Duration of Any Chest Drain In-situ Post-DR During hospitalization - up to 36 weeks Post Menstrual Age (PMA) Duration of any chest drain in-situ post-DR during hospitalization - up to 36 weeks Post Menstrual Age (PMA)
Death or Need for Positive Pressure Ventilation First 7 days of life Death or need for positive pressure ventilation during the first 7 days of life
Highest FiO2 and Area Under the FiO2 Curve for the First Week of Life First 7 days of life Highest FiO2 and Area under the FiO2 curve during the first 7 days of life
Pneumothorax or New Chest Drains in the First 48 Hours of Life First 48 hours of life Chest x-ray reports showing pneumothorax or new chest drains in the first 48 hours of life
Death in Hospital During expected hospitalization 23 - 40 weeks PMA Death in hospital during expected hospitalization of 23-40 weeks PMA
Heart Rate in the Delivery Room (DR) First 30 seconds of life in DR Categorical variable with 3 levels: \<60, 60-100, \>100
Need for Intubation in Delivery Room First 30 seconds to 24 hours of life Need for intubation in delivery room during the first 30 seconds to 24 hours of age
Intraventricular Hemorrhage by All Grades 48 hours to 10 days 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
Chest X-ray Between Days 7-10 First 7-10 days of life Chest x-ray between the first 7-10 days of life
Pneumothorax and Pulmonary Interstitial Emphysema (PIE) First 10 days of life Pneumothorax and pulmonary interstitial emphysema (PIE) during the first 10 days of life
Retinopathy of Prematurity (ROP) Stage 3 or Greater Requiring Treatment 36 weeks Retinopathy of prematurity (ROP) stage 3 or greater requiring treatment at 36 weeks
Oxygen Profile Over First 24 Hours First 24 hours post delivery Oxygen profile over first 24 hours post delivery room using hourly FiO2 records
Survival to Discharge Home Without BPD, Retinopathy of Prematurity (Grades 3 & 4), or Significant Brain Abnormalities on Head Ultrasound Expected discharge between 36 - 40 weeks PMA 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
Neurodevelopmental and Respiratory Outcome at 22-26 Months Corrected Gestational Age 22-26 months corrected gestational age Neurodevelopmental and respiratory outcome at 22-26 months corrected gestational age
Oxygen Profile With Highest FiO2 Level up to 48 Hours 48 hours of life Highest FiO2 level recorded during the first 48 hours post DR
Detailed Status on Departure From the Delivery Room (DR) Resuscitation time will vary - 1 to 30 minutes Type of respiratory support (CPAP, PPV) and Fraction of Inspired Oxygen (FiO2) on departure from DR
Use of Inotropes on Arrival in NICU First 48 hours of life Circulatory support post-delivery room
Pressure-volume Characteristics in the Delivery Room (DR) Expected average 30 minutes Pressure-volume characteristics in the Delivery room (DR) expected within 30 minutes
Duration of Respiratory Support (Ventilation, CPAP, Supplemental Oxygen) During hospitalization - up to 36 weeks Post Menstrual Age (PMA) Duration of respiratory support (ventilation, CPAP, supplemental oxygen) during hospitalization upto 36 weeks Post Menstrual Age (PMA)
Use of Postnatal Steroids for Treatment of BPD During hospitalization - up to 36 weeks Post Menstrual Age (PMA) Use of postnatal steroids for treatment of BPD during hospitalization up to 36 weeks Post Menstrual Age (PMA)
Length of Hospital Stay Average discharge between 36 - 40 weeks PMA Length of hospital stay with average discharge between 36-40 weeks PMA
Trial Locations
- Locations (21)
Sharp Mary Birch Hospital for Women & Newborns
🇺🇸San Diego, California, United States
KK Women's and Children's Hospital
🇸🇬Singapore, Singapore
Women & Infants Hospital of Rhode Island
🇺🇸Providence, Rhode Island, United States
University of California, Davis Children's Hospital
🇺🇸Sacramento, California, United States
Loma Linda University
🇺🇸Loma Linda, California, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Christiana Care
🇺🇸Newark, Delaware, United States
Wake Med Health
🇺🇸Raleigh, North Carolina, United States
Royal Women's Hospital
🇦🇺Melbourne, Australia
Hospital of the Univerity of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Mater Mother's Hospital
🇦🇺Brisbane, Queensland, Australia
Academic Teaching Hospital, Landeskrankenhaus Feldkirch
🇦🇹Feldkirch, Austria
Pennsylvania Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Royal Alexandra Hospital,
🇨🇦Edmonton, Canada
University of Freiburg
🇩🇪Freiburg, Germany
Children's Hospital, University of Ulm
🇩🇪Ulm, Germany
Seoul National University Children's Hospit
🇰🇷Seoul, Korea, Republic of
Ospedale dei Bambini
🇮🇹Milan, Italy
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Emma Children's Hospital, AMC
🇳🇱Amsterdam, Netherlands
Leiden University Medical Center
🇳🇱Leiden, Netherlands