Clinical trial NCT02139800: Sustained Aeration of Infant Lungs Trial
Official title: Sustained Aeration of Infant Lungs Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Preterm Birth
Extreme Prematurity
Keywords: Neonatal resuscitation
Extreme Low Gestational Age Newborn (ELGAN)
Delivery Room
Continuous positive airway pressure (CPAP)
Positive pressure ventilation (PPV)
Sustained inflation
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2014-05-15
Enrollment: 460
Sex: ALL
Minimum age (years): 23
Maximum age (years): 26
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Combined Outcome of Death or Bronchopulmonary Dysplasia
timeFrame: 36 weeks
Secondary outcomes:
measure: Oxygen Profile Over First 24 Hours
timeFrame: First 24 hours post delivery
measure: Oxygen Profile With Highest FiO2 Level up to 48 Hours
timeFrame: 48 hours of life
measure: Heart Rate in the Delivery Room (DR)
timeFrame: First 30 seconds of life in DR
measure: Detailed Status on Departure From the Delivery Room (DR)
timeFrame: Resuscitation time will vary - 1 to 30 minutes
measure: Use of Inotropes on Arrival in NICU
timeFrame: First 48 hours of life
measure: Need for Intubation in Delivery Room
timeFrame: First 30 seconds to 24 hours of life
measure: Pressure-volume Characteristics in the Delivery Room (DR)
timeFrame: Expected average 30 minutes
measure: Pneumothorax or New Chest Drains in the First 48 Hours of Life
timeFrame: First 48 hours of life
measure: Duration of Any Chest Drain In-situ Post-DR
timeFrame: During hospitalization - up to 36 weeks Post Menstrual Age (PMA)
measure: Intraventricular Hemorrhage by All Grades
timeFrame: 48 hours to 10 days
measure: Chest X-ray Between Days 7-10
timeFrame: First 7-10 days of life
measure: Death or Need for Positive Pressure Ventilation
timeFrame: First 7 days of life
measure: Highest FiO2 and Area Under the FiO2 Curve for the First Week of Life
timeFrame: First 7 days of life
measure: Pneumothorax and Pulmonary Interstitial Emphysema (PIE)
timeFrame: First 10 days of life
measure: Survival to Discharge Home Without BPD, Retinopathy of Prematurity (Grades 3 & 4), or Significant Brain Abnormalities on Head Ultrasound
timeFrame: Expected discharge between 36 - 40 weeks PMA
measure: Duration of Respiratory Support (Ventilation, CPAP, Supplemental Oxygen)
timeFrame: During hospitalization - up to 36 weeks Post Menstrual Age (PMA)
measure: Death in Hospital
timeFrame: During expected hospitalization 23 - 40 weeks PMA
measure: Retinopathy of Prematurity (ROP) Stage 3 or Greater Requiring Treatment
timeFrame: 36 weeks
measure: Use of Postnatal Steroids for Treatment of BPD
timeFrame: During hospitalization - up to 36 weeks Post Menstrual Age (PMA)
measure: Length of Hospital Stay
timeFrame: Average discharge between 36 - 40 weeks PMA
measure: Neurodevelopmental and Respiratory Outcome at 22-26 Months Corrected Gestational Age
timeFrame: 22-26 months corrected gestational age
Other outcomes:
Locations:
city: Loma Linda
country: United States
facility: Loma Linda University
state: California
city: Sacramento
country: United States
facility: University of California, Davis Children's Hospital
state: California
city: San Diego
country: United States
facility: Sharp Mary Birch Hospital for Women & Newborns
state: California
city: Newark
country: United States
facility: Christiana Care
state: Delaware
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Raleigh
country: United States
facility: Wake Med Health
state: North Carolina
city: Philadelphia
country: United States
facility: Hospital of the Univerity of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Pennsylvania Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Women & Infants Hospital of Rhode Island
state: Rhode Island
city: Brisbane
country: Australia
facility: Mater Mother's Hospital
state: Queensland
city: Melbourne
country: Australia
facility: Royal Women's Hospital
city: Feldkirch
country: Austria
facility: Academic Teaching Hospital, Landeskrankenhaus Feldkirch
city: Edmonton
country: Canada
facility: Royal Alexandra Hospital,
city: Freiburg
country: Germany
facility: University of Freiburg
city: Ulm
country: Germany
facility: Children's Hospital, University of Ulm
city: Milan
country: Italy
facility: Ospedale dei Bambini
city: Seoul
country: Korea, Republic of
facility: Seoul National University Children's Hospit
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Amsterdam
country: Netherlands
facility: Emma Children's Hospital, AMC
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Singapore
country: Singapore
facility: KK Women's and Children's Hospital
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Haresh Kirpalani, BM, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal Women's Hospital, Melbourne, Australia
name: Peter Davis, MD, FRAXP
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital, University of Ulm, Ulm Germany
name: Helmut Hummler, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Women & Infants Hospital of Rhode Island, Providence, RI
name: Martin Keszler, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale dei Bambini, Milan Italy
name: GianLuca Lista, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Leiden University Medical Center, Leiden, Netherlands
name: Arjan te_Pas, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.