Study of Room Air Versus 60% Oxygen for Resuscitation of Premature Infants (PRESOX)

The Premature Infants Resuscitated With Oxygen or Air (PRESOX) Trial

The most appropriate initial oxygen concentration for the resuscitation of the extremely low birth weight infant has not been established using large well designed, randomized, blinded, prospective trials and the level of oxygen utilized by practitioners in this situation is highly variable. This proposed trial will use targeted oxygen saturation levels over the first 15 to 20 minutes of life to compare a low and a higher initial oxygen level for the resuscitation of such infants, and will be large enough to evaluate short term outcomes of survival without oxygen at 36 weeks and survival without retinopathy of prematurity, and the long term outcome of survival without significant neurodevelopmental impairment at 2 years of age. Such information is urgently required to provide an evidence basis for the initial oxygen concentration for resuscitation of these very preterm infants.

Study Overview

• Status: Terminated
• Conditions: Extreme Prematurity - Less Than 28 Weeks
• Intervention / Treatment: Other: Neonatal Resuscitation

Detailed Description

The Premature Infants Resuscitated with Oxygen or Air (PRESOX) trial, is a prospective randomized clinical trial of extremely premature infants that will assess the use of a low and high oxygen concentration for the initial resuscitation. The hypothesis is that infants resuscitated with a lower oxygen concentration at birth will have a increase in survival without bronchopulmonary dysplasia (BPD) or retinopathy of prematurity (ROP) during their initial hospitalization, and will have a increase in survival without neurodevelopmental impairments.

Previous studies of mostly term newborn infants have demonstrated that initial resuscitation with room air compared to 100% oxygen resulted in improved outcomes and an overall decrease in mortality. The analysis of these studies demonstrated that the reduction in mortality was very significant in the preterm infants that had been included in these trials. A number of small clinical trials have now demonstrated that it is feasible to treat very preterm infants with lower versus higher concentrations of oxygen while carefully monitoring their oxygen saturation in the minutes following delivery. As review of the previous observations demonstrated that there was a reduction in death using lower oxygen concentration, it is imperative that a large study of preterm infants be conducted to determine if a lower compared to a higher oxygen concentration for the initial resuscitation will lead to improved short and longer term outcomes including survival without neurodevelopmental disability.

The PRESOX trial will randomize infants from 23 weeks gestation to 28 weeks gestation who require resuscitation at birth to receive either room air or 60% oxygen. Oxygen saturation will be monitored from the first minute of life and the initial oxygen concentration will be titrated using a unique purpose built device which will track the oxygen saturation (SpO2) within the chosen target limits. The targets chosen allow the infants oxygen saturation to follow the increase seen in normal preterm infants who do not require resuscitation. Following resuscitation the infants will be transferred to the Neonatal Intensive Care Unit and management will follow the usual care in those units. In a subset of infants, levels of antioxidants from the infant's blood and urine will be measured by Dr M Vento. This portion of the study is already funded by the combined Spanish Ministries of Health and Science. Antioxidants are known to increase with exposure to oxygen. The infants will return for a neurodevelopmental follow up examination at the age of two years.

This trial will provide urgently needed evidence to establish the most optimal care to these very fragile preterm infants.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria
    • Innsbruck Medical University
  • Vienna, Austria, 1090
    • Medical University of Vienna
• France
  • Toulouse, France
    • Chu-Toulouse
• Germany
  • Ulm, Germany
    • Ulm University
• Ireland
  • Dublin, Ireland
    • National Maternity Hospital
• Italy
  • Milan, Italy
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
  • Sienna, Italy
    • University of Siena
• Poland
  • Poznan, Poland
    • Poznan University of Medical Sciences
• Russian Federation
  • St. Petersberg, Russian Federation
    • St. Petersberg State Pediatric Medical University
• Slovenia
  • Ljubljana, Slovenia
    • University Medical Center Ljubljana
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain
    • Hospital Saint Joan de Deu
  • Madrid, Spain
    • Hospital Clinico San Carlos
  • Valencia, Spain
    • Hospital la Fé
• Sweden
  • Stockholm, Sweden
    • Karolinska Institutet
• United Kingdom
  • Middlesbrough, United Kingdom
    • James Cook University Hospital
• United States
  • California
    • San Diego, California, United States, 92123
      • Sharp Mary Birch Hospital for Women and Newborns
  • Connecticut
    • Farmington, Connecticut, United States, 06030-2948
      • Connecticut Children's Medical Center
  • Florida
    • Miami, Florida, United States, 33101
      • University of Miami Miller School of Medicine
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University Health Sciences Center
    • Tulsa, Oklahoma, United States, 74135
      • OU - Tulsa - Saint Francis Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Infants with a gestational age of 23 0/7 to 28 6/7 weeks by best obstetrical estimate.

Infants who will receive full resuscitation as necessary, i.e., no parental request or physician decision to forego resuscitation Infants whose parents/legal guardians have provided consent for enrollment, or for whom a waiver of consent is in place Infants without known major congenital malformations prior to delivery

Exclusion Criteria:

Any infant transported to the center after delivery Infants whose parents/legal guardians refuse consent Infants born when the research apparatus/study personnel are not available Infants < 23 weeks 0 days or > 28 weeks 6 days, completed weeks of gestation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Room Air; Neonatal Resuscitation using continuous positive airway pressure(CPAP) or positive pressure ventilation (PPV) will be provided with 21% oxygen. Infants will remain on 21% oxygen until they have a functioning oximeter when SpO2 will be managed as below. FiO2 will be increased by 10% increments when the infant's SpO2 is below the lower sat limit for 30 seconds and repeated if the SpO2 remains outside the limit for a subsequent interval of 30 seconds as often as is necessary to bring the SpO2 within the pre-specified range. The FiO2 will be decreased by 10% increments when the SpO2 is above the upper limit for 30 seconds and repeated if the SpO2 remains outside the limit for a subsequent interval of 30 second as often as is necessary to bring the SpO2 within the pre-specified range.	Other: Neonatal Resuscitation; CPAP or Positive Pressure Ventilation will be provided.
Active Comparator: 60% Group; Neonatal Resuscitation using CPAP or PPV will be provided with 60% oxygen. Infants will remain on 60% oxygen until they have a functioning oximeter at which time their SpO2 will be managed as described below FiO2 will be increased by 10% increments when the infant's SpO2 is below the lower sat limit for 30 seconds and repeated if the SpO2 remains outside the limit for a subsequent interval of 30 seconds as often as is necessary to bring the SpO2 within the pre-specified range. The FiO2 will be decreased by 10% increments when the SpO2 is above the upper limit for 30 seconds and repeated if the SpO2 remains outside the limit for a subsequent interval of 30 second as often as is necessary to bring the SpO2 within the pre-specified range.	Other: Neonatal Resuscitation; CPAP or Positive Pressure Ventilation will be provided.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival with neurodevelopmental impairment	To determine if resuscitation starting with 21% oxygen and a targeted SpO2 strategy will increase survival without significant neurodevelopmental impairment at 18 to 22 months when compared with starting with 60% oxygen and a targeted SpO2 strategy.	18-22 mos.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival without bronchopulmonary dysplasia	2. To determine if resuscitation of extremely low gestational age neonates (ELGAN) starting with 21% oxygen and a targeted SpO2 strategy will increase survival without bronchopulmonary dysplasia when compared with starting with 60% oxygen and a targeted SpO2 strategy.	36 weeks
Survival without ROP	3. To determine if resuscitation of extremely low gestational age neonates (ELGAN) starting with 21% oxygen and a targeted SpO2 strategy will increase survival without Retinopathy of Prematurity when compared with starting with 60% oxygen and a targeted SpO2 strategy.	36 weeks
Decreased GSSG/GSH Ratio	4. To determine if resuscitation starting with 21% oxygen and a targeted SpO2 strategy will result in decreased GSSG/GSH ratio concentrations and decreased production of isofurans when compared with starting with 60% oxygen and a targeted SpO2 strategy.	Birth,1,3,7 days

Collaborators and Investigators

• Sponsor: Sharp HealthCare
• Collaborators: Thrasher Research Fund
• Investigators: Principal Investigator: Neil N Finer, MD, UCSD Medical Center; Principal Investigator: Maximo Vento, MD, Hospital La Fe, Valencia Spain; Principal Investigator: Ola D Saugstad, MD, PhD, The National Hospital, Oslo Norway

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): March 1, 2017
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: January 10, 2013
• First Submitted That Met QC Criteria: January 18, 2013
• First Posted (Estimate): January 23, 2013

Study Record Updates

• Last Update Posted (Actual): September 12, 2018
• Last Update Submitted That Met QC Criteria: September 10, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: neonatal; resuscitation; room air
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth
• Other Study ID Numbers: 2012-3602