Sustained Aeration of Infant Lungs Trial (SAIL)

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

Study Overview

• Status: Completed
• Conditions: Preterm Birth; Extreme Prematurity
• Intervention / Treatment: Procedure: Standard of Care; Procedure: Sustained Inflation

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.

• Study Type: Interventional
• Enrollment (Actual): 460
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Melbourne, Australia
    • Royal Women's Hospital
  • Queensland
    • Brisbane, Queensland, Australia, QLD 4101
      • Mater Mother's Hospital
• Austria
  • Feldkirch, Austria
    • Academic Teaching Hospital, Landeskrankenhaus Feldkirch
• Canada
  • Edmonton, Canada
    • Royal Alexandra Hospital,
• Germany
  • Freiburg, Germany
    • University of Freiburg
  • Ulm, Germany
    • Children's Hospital, University of Ulm
• Italy
  • Milan, Italy
    • Ospedale dei Bambini
• Korea, Republic of
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Children's Hospit
• Netherlands
  • Amsterdam, Netherlands
    • Emma Children's Hospital, AMC
  • Leiden, Netherlands
    • Leiden University Medical Center
• Singapore
  • Singapore, Singapore, 168753
    • KK Women's and Children's Hospital
• United States
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University
    • Sacramento, California, United States, 95817
      • University of California, Davis Children's Hospital
    • San Diego, California, United States, 92123
      • Sharp Mary Birch Hospital for Women & Newborns
  • Delaware
    • Newark, Delaware, United States, 19713
      • Christiana Care
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • North Carolina
    • Raleigh, North Carolina, United States, 27610
      • Wake Med Health
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Pennsylvania Hospital
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the Univerity of Pennsylvania
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Women & Infants Hospital of Rhode Island

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 5 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control Arm-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	Procedure: Standard of Care; Newborn Resuscitation Program (NRP) Guidelines using a standard PEEP/CPAP of 5-7 cm H2O as compared to the Sustained Inflation intervention
Experimental: Sustained Intervention; 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; The first sustained inflation will use inflation pressure of 20 cm H20 for 15 seconds

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: Haresh Kirpalani, BM, MSc, Children's Hospital of Philadelphia; Principal Investigator: Peter Davis, MD, FRAXP, Royal Women's Hospital, Melbourne, Australia; Principal Investigator: Helmut Hummler, MD, Children's Hospital, University of Ulm, Ulm Germany; Principal Investigator: Martin Keszler, MD, Women & Infants Hospital of Rhode Island, Providence, RI; Principal Investigator: GianLuca Lista, MD, Ospedale dei Bambini, Milan Italy; Principal Investigator: Arjan te_Pas, MD, Leiden University Medical Center, Leiden, Netherlands

Publications and helpful links

General Publications

• Foglia EE, Kirpalani H, Ratcliffe SJ, Davis PG, Thio M, Hummler H, Lista G, Cavigioli F, Schmolzer GM, Keszler M, Te Pas AB. Sustained Inflation Versus Intermittent Positive Pressure Ventilation for Preterm Infants at Birth: Respiratory Function and Vital Sign Measurements. J Pediatr. 2021 Dec;239:150-154.e1. doi: 10.1016/j.jpeds.2021.08.038. Epub 2021 Aug 25.
• Kirpalani H, Keszler M, Foglia EE, Davis P, Ratcliffe S. Considering the Validity of the SAIL Trial-A Navel Gazers Guide to the SAIL Trial. Front Pediatr. 2019 Nov 27;7:495. doi: 10.3389/fped.2019.00495. eCollection 2019.
• Kirpalani H, Ratcliffe SJ, Keszler M, Davis PG, Foglia EE, Te Pas A, Fernando M, Chaudhary A, Localio R, van Kaam AH, Onland W, Owen LS, Schmolzer GM, Katheria A, Hummler H, Lista G, Abbasi S, Klotz D, Simma B, Nadkarni V, Poulain FR, Donn SM, Kim HS, Park WS, Cadet C, Kong JY, Smith A, Guillen U, Liley HG, Hopper AO, Tamura M; SAIL Site Investigators. Effect of Sustained Inflations vs Intermittent Positive Pressure Ventilation on Bronchopulmonary Dysplasia or Death Among Extremely Preterm Infants: The SAIL Randomized Clinical Trial. JAMA. 2019 Mar 26;321(12):1165-1175. doi: 10.1001/jama.2019.1660.
• Foglia EE, Te Pas AB. Sustained Lung Inflation: Physiology and Practice. Clin Perinatol. 2016 Dec;43(4):633-646. doi: 10.1016/j.clp.2016.07.002.
• Foglia EE, Owen LS, Thio M, Ratcliffe SJ, Lista G, Te Pas A, Hummler H, Nadkarni V, Ades A, Posencheg M, Keszler M, Davis P, Kirpalani H. Sustained Aeration of Infant Lungs (SAIL) trial: study protocol for a randomized controlled trial. Trials. 2015 Mar 15;16:95. doi: 10.1186/s13063-015-0601-9.

Study record dates

Study Major Dates

• Study Start (Actual): August 27, 2014
• Primary Completion (Actual): February 15, 2018
• Study Completion (Actual): March 23, 2020

Study Registration Dates

• First Submitted: May 8, 2014
• First Submitted That Met QC Criteria: May 13, 2014
• First Posted (Estimate): May 15, 2014

Study Record Updates

• Last Update Posted (Actual): April 6, 2023
• Last Update Submitted That Met QC Criteria: April 4, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Continuous positive airway pressure (CPAP); Neonatal resuscitation; Delivery Room; Extreme Low Gestational Age Newborn (ELGAN); Positive pressure ventilation (PPV); Sustained inflation
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth
• Other Study ID Numbers: 819208; 1U01HD072906-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED