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Trial registered on ANZCTR


Registration number
ACTRN12610001059055
Ethics application status
Approved
Date submitted
19/08/2010
Date registered
2/12/2010
Date last updated
15/05/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
The To2rpido Study: Targeted Oxygenation in the Resuscitation of Premature Infants and their Developmental Outcome
Scientific title
The To2rpido Study: Targeted Oxygenation in the Resuscitation of Premature Infants and their Developmental Outcome
Secondary ID [1] 252517 0
Nil current
Universal Trial Number (UTN)
Trial acronym
Torpido study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Oxidative stress in premature infants 258007 0
Mortality in premature infants 258008 0
Bronchopulmonary dysplasia in premature infants 258009 0
Extreme prematurity 258010 0
Resuscitation in premature infants 258011 0
Condition category
Condition code
Respiratory 258176 258176 0 0
Other respiratory disorders / diseases
Reproductive Health and Childbirth 258881 258881 0 0
Other reproductive health and childbirth disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Starting delivery room resuscitation of premature infants below 31 weeks completed gestation with room air and titrating to specific postnatal oxygen saturations. This is a once off intervention. Management after the infant leaves the delivery room will be as per institutional guidelines
Intervention code [1] 257051 0
Treatment: Other
Intervention code [2] 257677 0
Other interventions
Comparator / control treatment
The use of pure oxygen is the standard of care for newborn resuscitation. Room air for preterm infants during resuscitation will be used in the other arm. Infants will be allocated to start resuscitation with either room air or pure oxygen. FiO2 in each arm will be titrated to set levels ot oxygen saturations via a preductal monitor. This intervention will last about 20-30 minutes (average duration of resuscitation in the delivery room). The intervention occurs only once, at birth. Infants in the room air arm may cross over to pure oxygen if 1. The oxygen saturations remain below 65% at 5 minutes of age 2. The infant requires cardiac compression or inotropic agents.
Control group
Active

Outcomes
Primary outcome [1] 259035 0
Mortality
Timepoint [1] 259035 0
2 years of age
Secondary outcome [1] 265280 0
Major disability as assessed by the Bayley Scare of Infant Development III
Timepoint [1] 265280 0
2 years of age
Secondary outcome [2] 265281 0
Bronchopulmonary dysplasia, as assessed by the need for supplemental oxygen and/or ventilatory support at 36 weeks corrected gestation
Timepoint [2] 265281 0
36 weeks corrected gestation

Eligibility
Key inclusion criteria
Birth below 31 weeks completed gestation and/or birthweight below 1250g if gestation is unknown.
Minimum age
0 Hours
Maximum age
31 Weeks
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Major congenital abnormalities resulting in certain death and/or developmental delay and/or oxygen metabolism and distribution

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Mother at risk of preterm delivery before 31 weeks completed gestation is approached and provided information about the study. Approach is not to be attempted if delivery is imminent or <6 hours after admission of the mother to the hospital. Randomisation occurs at the time of delivery from sealed opaque envelopes containing a centrally generated randomised code.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated randomisation allocated to specific centres and stratified by gestation.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Cross over to pure oxygen permitted if room air infant fails to meet the following criteria:
1. Heart rate <100beats per minute despite adequate ventilation and/or
2. Oxygen saturations is<65% at or after 5 minutes [FiO2 - fractional inspired oxygen: 0.5 – 0.7 at 5 minutes]
3. If external cardiac message or resuscitation medications required at any time
Phase
Phase 2 / Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
3/12/2010
Actual
3/12/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
1892
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 3149 0
2031
Recruitment outside Australia
Country [1] 2823 0
Malaysia
State/province [1] 2823 0
Selangor

Funding & Sponsors
Funding source category [1] 257499 0
Hospital
Name [1] 257499 0
Leslie Stevens Fund for Newborn Research
Country [1] 257499 0
Australia
Primary sponsor type
Hospital
Name
The Royal Hospital for Women
Address
Barker St
Randwick NSW 2031
Country
Australia
Secondary sponsor category [1] 256731 0
Government body
Name [1] 256731 0
Ministry of Health Malaysia
Address [1] 256731 0
Ministry of Health Malaysia,
Blok E1, E6 & E10 Kompleks E,
Pusat Pentadbiran Kerajaan Persekutuan,
62590 Putrajaya, Malaysia
Country [1] 256731 0
Malaysia
Other collaborator category [1] 251449 0
University
Name [1] 251449 0
University of Malaya
Address [1] 251449 0
Pusat Perubatan Universiti Malaya,
Lembah Pantai,
59100, Kuala Lumpur,
Malaysia
Country [1] 251449 0
Malaysia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 259527 0
South East Sydney Health Service
Ethics committee address [1] 259527 0
Prince of Wales Hospital
High St
Randwick NSW 2031
Ethics committee country [1] 259527 0
Australia
Date submitted for ethics approval [1] 259527 0
20/02/2006
Approval date [1] 259527 0
28/06/2006
Ethics approval number [1] 259527 0
1/06/0065

Summary
Brief summary
The problem with oxygen: Oxygen (O2) is essential for life but too much (hyperoxia) is toxic and may cause cell inflammation and death. The extremely premature infant is particularly susceptible to O2 toxicity because they do not develop or acquire appropriate defense mechanisms until the 3rd trimester (after 28 weeks gestation). Prolonged or excessive exposure to O2 may, in fact, cause problems like bronchopulmonary dysplasia (BPD) or retinopathy of prematurity (ROP). Children with BPD are in and out of hospitals with chest infections and asthma. They also have lower intelligence and grow more poorly because of repeated episodes of hypoxia (low body O2) from lung damage and steroids. The latter improves lung function but may also impair brain growth. Children with ROP may be severely short-sighted and even blind. Unfortunately, many premature infants, if they survive, still develop BPD and ROP despite considerable advances in prenatal care (e.g. maternal steroids that accelerate lung maturation), postnatal care (e.g. artificial surfactant that aids lung expansion) and an awareness of the profound consequences of O2 toxicity in this population.
The use of oxygen during resuscitation: More than 1 million infants around the world do not breathe after birth and require resuscitation. For more than a century, pure or 100% O2 has been given to such infants through breathing masks or tubes. A change in color from blue or white to pink is generally taken to be a positive response to resuscitation. However, recent studies of full-term human newborn infants now advocate caution because there is increasing evidence giving an infant 100% O2 may cause excessive formation of toxic reactive oxygen species (ROS) that injure vital cellular components like membranes and DNA (deoxyribonucleic acid). This may delay the infant’s recovery and even double the risk of death.
What about the premature infant? Studies have shown that full-term infants may be resuscitated with room air (RA, 21% O2) with good result. However, premature infants often have some lung immaturity and may need a bit of O2 after birth to prevent hypoxia. How much O2 that is, is not certain. Whether giving a preterm infant lower amounts of O2 during resuscitation may improve outcome is also not known.
The aim of the To2rpido study is to see if using RA to start the resuscitation of very premature infants (<31 weeks gestation) reduces oxidative injury and complications such as BPD, ROP, cerebral palsy (CP) and death.
Location: This is an international study in Australia (n=3), Malaysia (n=6), Singapore (n=1) and India (n=1). These sites are important to show that the resuscitation techniques used in the To2rpido study may be applied to neonatal intensive care units in both developed and developing nations.
How the study will be conducted: We will compare RA to 100% O2 to start the resuscitation of premature infants below 31 weeks gestation in the delivery suite. O2 will be changed depending on the infant’s oxygen saturations (percentage of oxygenated hemoglobin, SaO2) and the infant’s blood will be tested for O2-related stress products. Complications such as death, CP, BPD and ROP will be compared and survivors will be tested at 18-24 months of age for neurological and physical development.
Significance: There is still no cure for prematurity, which affects more than 8% of infants worldwide. The number of premature infants has increased by 15% over the last two decades in the USA alone and their care costs more than $30 billion a year. In addition, most of the premature babies are born in non-Western countries and the techniques used in the To2rpido may therefore also have far-reaching consequences for the almost 13 million premature infants born around the world each year.
Trial website
Nil current
Trial related presentations / publications
Presentations entitled: The To2rpido Study: Targeted Oxygenation in the Resuscitation of Premature Infants and their Developmental Outcome at:
1. Perinatal Society Meeting, Malaysia, March 2009
2. Congress of the Perinatal Society of Australia and New Zealand, April 2009.
Public notes

Contacts
Principal investigator
Name 31548 0
Dr Julee Oei
Address 31548 0
Newborn Care Centre
Royal Hospital for Women
Barker St
Randwick NSW 2031
Country 31548 0
Australia
Phone 31548 0
+612 9385 6152
Fax 31548 0
Email 31548 0
j.oei@unsw.edu.au
Contact person for public queries
Name 14795 0
Dr Julee Oei
Address 14795 0
The Royal Hospital for Women
Barker St
Randwick NSW 2031
Country 14795 0
Australia
Phone 14795 0
61 2 9382 6152
Fax 14795 0
61 2 9382 6191
Email 14795 0
Ju.oei@sesiahs.health.nsw.gov.au
Contact person for scientific queries
Name 5723 0
Dr Julee Oei
Address 5723 0
The Royal Hospital for Women
Barker St
Randwick NSW 2031
Country 5723 0
Australia
Phone 5723 0
61 2 9382 6152
Fax 5723 0
61 2 9382 6191
Email 5723 0
ju.oei@sesiahs.health.nsw.gov.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbasePreterm infant outcomes after randomisation to initial resuscitation with FiO2 0.21 or 1.0.2018https://dx.doi.org/10.1111/jpc.13882_121
EmbasePreterm Infant Outcomes after Randomization to Initial Resuscitation with FiO2 0.21 or 1.0.2018https://dx.doi.org/10.1016/j.jpeds.2018.05.053
EmbaseHigher or lower oxygen for delivery room resuscitation of preterm infants below 28 completed weeks gestation: A meta-analysis.2017https://dx.doi.org/10.1136/archdischild-2016-310435
N.B. These documents automatically identified may not have been verified by the study sponsor.