Sustained Aeration of Infant Lungs Trial

ID: NCT02139800
Status: Active, not recruiting
Phase: N/A
Start Date: August 27, 2014
First Submitted: May 08, 2014
Last Updated: February 14, 2018
Results: N/A
Sponsors & Collaborators: University of Pennsylvania, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Location: Australia, Austria, Canada, Germany, Italy, Korea, Republic of, Netherlands, Singapore, United States
Conditions: Preterm Birth, Extreme Prematurity
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Study Description

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.
Condition or disease Intervention/treatment Phase

Extreme Prematurity

Preterm Birth

Procedure: Sustained Inflation
Other Names
Procedure: Standard of Care
Other Names
N/A

Tracking Information

First Submitted DateMay 08, 2014
Last Update Posted DateFebruary 14, 2018
Actual Start DateAugust 27, 2014
Anticipated Completion DateMarch 01, 2020
Actual Primary Completion DateNovember 23, 2017
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Combined outcome of death or bronchopulmonary dysplasia [Time Frame: 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.

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Oxygen profile over first 24 hours post delivery room using hourly FiO2 records [Time Frame: First 24 hours post delivery]

  • Oxygen profile with highest FiO2 level up to 48 hours [Time Frame: 48 hours of life]

    Highest FiO2 level recorded during the first 48 hours post DR

  • Heart rate in the Delivery Room (DR) [Time Frame: First 30 seconds of life in DR]

    Categorical variable with 3 levels: <60, 60-100, >100

  • Detailed status on departure from the Delivery room (DR) [Time Frame: 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 [Time Frame: First 48 hours of life]

    Circulatory support post-delivery room

  • Need for intubation in delivery room or by 24 hours of age [Time Frame: First 30 seconds to 24 hours of life]

  • Pressure-volume characteristics in the Delivery room (DR) [Time Frame: Expected average 30 minutes]

  • Chest x-ray reports showing pneumothorax or new chest drains in the first 48 hours of life [Time Frame: First 48 hours of life]

  • Duration of any chest drain in-situ post-DR [Time Frame: During hospitalization - up to 36 weeks Post Menstrual Age (PMA)]

  • 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 [Time Frame: 48 hours to 10 days]

  • Chest x-ray between days 7-10 [Time Frame: First 7-10 days of life]

  • Death or need for positive pressure ventilation at 7 days [Time Frame: First 7 days of life]

  • Highest FiO2 and Area under the FiO2 curve for the first week of life [Time Frame: First 7 days of life]

  • Pneumothorax and pulmonary interstitial emphysema (PIE) [Time Frame: First 10 days of life]

  • Survival to discharge home without BPD, retinopathy of prematurity (grades 3 & 4), or significant brain abnormalities on head ultrasound [Time Frame: Expected discharge between 36 - 40 weeks PMA]

  • Duration of respiratory support (ventilation, CPAP, supplemental oxygen) [Time Frame: During hospitalization - up to 36 weeks Post Menstrual Age (PMA)]

  • Death in hospital [Time Frame: During expected hospitalization 23 - 40 weeks PMA]

  • Retinopathy of prematurity (ROP) stage 3 or greater requiring treatment [Time Frame: 36 weeks]

  • Use of postnatal steroids for treatment of BPD [Time Frame: During hospitalization - up to 36 weeks Post Menstrual Age (PMA)]

  • Length of hospital stay [Time Frame: Average discharge between 36 - 40 weeks PMA]

  • Neurodevelopmental and respiratory outcome at 22-26 months corrected gestational age [Time Frame: 22-26 months corrected gestational age]

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleSustained Aeration of Infant Lungs Trial
Official TitleSustained Aeration of Infant Lungs Trial
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.

Study TypeInterventional
Study PhaseN/A
Estimated Enrollment
460
Allocation
Randomized
Interventional Model
Parallel Assignment
Masking
None (Open Label)
Primary Purpose
Treatment
Conditions
Extreme Prematurity
Preterm Birth
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Procedure: Sustained Inflation

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

Other Names
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

Other Names
Study Groups/Cohorts
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

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

Study Arms
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

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
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

Recruitment Information

Recruitment Status:Active, not recruiting
Enrollment460
Completion DateMarch 01, 2020
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
GenderAll
Age23 Weeks to 26 Weeks
Accepts Healthy VolunteersNo
Contacts
Not Available
Listed Location Countries
Australia
Austria
Canada
Germany
Italy
Korea, Republic of
Netherlands
Singapore
United States

Administrative Information

NCT Number:NCT02139800
Other Study ID Numbers
819208
1U01HD072906-01A1
Has Data Monitoring CommitteeYes
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
University of Pennsylvania
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Principal Investigator
Arjan te_Pas, MD
Leiden University Medical Center, Leiden, Netherlands
Principal Investigator
GianLuca Lista, MD
Ospedale dei Bambini, Milan Italy
Principal Investigator
Haresh Kirpalani, BM, MSc
Children's Hospital of Philadelphia
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
Peter Davis, MD, FRAXP
Royal Women's Hospital, Melbourne, Australia