Sustained Aeration of Infant Lungs Trial

NCT ID: NCT02139800

Last Updated: 2023-04-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 460 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-08-27
• Study Completion Date: 2020-03-23

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.

Conditions

Preterm Birth; Extreme Prematurity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Standard of Care

Intervention Type: PROCEDURE

Newborn Resuscitation Program (NRP) Guidelines using a standard PEEP/CPAP of 5-7 cm H2O as compared to the Sustained Inflation intervention

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

Group Type: EXPERIMENTAL

Sustained Inflation

Intervention Type: PROCEDURE

The first sustained inflation will use inflation pressure of 20 cm H20 for 15 seconds

Interventions

Sustained Inflation

The first sustained inflation will use inflation pressure of 20 cm H20 for 15 seconds

Intervention Type: 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

Intervention Type: PROCEDURE

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

• Minimum Eligible Age: 23 Weeks
• Maximum Eligible Age: 26 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Haresh Kirpalani, BM, MSc

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Peter Davis, MD, FRAXP

Role: PRINCIPAL_INVESTIGATOR

Royal Women's Hospital, Melbourne, Australia

Helmut Hummler, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital, University of Ulm, Ulm Germany

Martin Keszler, MD

Role: PRINCIPAL_INVESTIGATOR

Women & Infants Hospital of Rhode Island, Providence, RI

GianLuca Lista, MD

Role: PRINCIPAL_INVESTIGATOR

Ospedale dei Bambini, Milan Italy

Arjan te_Pas, MD

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center, Leiden, Netherlands

Locations

Loma Linda University

Loma Linda, California, United States

University of California, Davis Children's Hospital

Sacramento, California, United States

Sharp Mary Birch Hospital for Women & Newborns

San Diego, California, United States

Christiana Care

Newark, Delaware, United States

University of Michigan

Ann Arbor, Michigan, United States

Wake Med Health

Raleigh, North Carolina, United States

Hospital of the Univerity of Pennsylvania

Philadelphia, Pennsylvania, United States

Pennsylvania Hospital

Philadelphia, Pennsylvania, United States

Women & Infants Hospital of Rhode Island

Providence, Rhode Island, United States

Mater Mother's Hospital

Brisbane, Queensland, Australia

Royal Women's Hospital

Melbourne, , Australia

Academic Teaching Hospital, Landeskrankenhaus Feldkirch

Feldkirch, , Austria

Royal Alexandra Hospital,

Edmonton, , Canada

University of Freiburg

Freiburg im Breisgau, , Germany

Children's Hospital, University of Ulm

Ulm, , Germany

Ospedale dei Bambini

Milan, , Italy

Emma Children's Hospital, AMC

Amsterdam, , Netherlands

Leiden University Medical Center

Leiden, , Netherlands

KK Women's and Children's Hospital

Singapore, , Singapore

Seoul National University Children's Hospit

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Countries

United States; Australia; Austria; Canada; Germany; Italy; Netherlands; Singapore; South Korea

References

Owen LS, Foglia EE, Ratcliffe SJ, Simma B, Katheria AC, Te Pas A, Onland W, van Kaam AH, Keszler M, Kirpalani H, Davis PG. Alternative consent processes in a neonatal resuscitation trial (SAIL): secondary analysis of an open-label, international, multicentre, randomised trial. Lancet Child Adolesc Health. 2025 Oct;9(10):698-706. doi: 10.1016/S2352-4642(25)00185-3. Epub 2025 Aug 12.

Reference Type: DERIVED

PMID: 40816312 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34453917 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31828052 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30912836 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27837749 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25872563 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

1U01HD072906-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

819208

Identifier Type: -

Identifier Source: org_study_id