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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]

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

Mortality in premature infants

Bronchopulmonary dysplasia in premature infants

Extreme prematurity

Resuscitation in premature infants

Condition category

Condition code

Respiratory

Other respiratory disorders / diseases

Reproductive Health and Childbirth

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]

Treatment: Other

Intervention code [2]

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]

Mortality

Timepoint [1]

2 years of age

Secondary outcome [1]

Major disability as assessed by the Bayley Scare of Infant Development III

Timepoint [1]

2 years of age

Secondary outcome [2]

Bronchopulmonary dysplasia, as assessed by the need for supplemental oxygen and/or ventilatory support at 36 weeks corrected gestation

Timepoint [2]

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?

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]

2031

Recruitment outside Australia

Country [1]

Malaysia

State/province [1]

Selangor

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Leslie Stevens Fund for Newborn Research

Address [1]

Sydney Childrens Hospital
High St
Randwick NSW 2031

Country [1]

Australia

Primary sponsor type

Hospital

Name

The Royal Hospital for Women

Address

Barker St
Randwick NSW 2031

Country

Australia

Secondary sponsor category [1]

Government body

Name [1]

Ministry of Health Malaysia

Address [1]

Ministry of Health Malaysia,
Blok E1, E6 & E10 Kompleks E,
Pusat Pentadbiran Kerajaan Persekutuan,
62590 Putrajaya, Malaysia

Country [1]

Malaysia

Other collaborator category [1]

University

Name [1]

University of Malaya

Address [1]

Pusat Perubatan Universiti Malaya,
Lembah Pantai,
59100, Kuala Lumpur,
Malaysia

Country [1]

Malaysia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

South East Sydney Health Service

Ethics committee address [1]

Prince of Wales Hospital
High St
Randwick NSW 2031

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

20/02/2006

Approval date [1]

28/06/2006

Ethics approval number [1]

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

Dr Julee Oei

Address

Newborn Care Centre
Royal Hospital for Women
Barker St
Randwick NSW 2031

Country

Australia

Phone

+612 9385 6152

Fax

j.oei@unsw.edu.au

Contact person for public queries

Name

Julee Oei

Address

The Royal Hospital for Women
Barker St
Randwick NSW 2031

Country

Australia

Phone

61 2 9382 6152

Fax

61 2 9382 6191

Ju.oei@sesiahs.health.nsw.gov.au

Contact person for scientific queries

Name

Julee Oei

Address

The Royal Hospital for Women
Barker St
Randwick NSW 2031

Country

Australia

Phone

61 2 9382 6152

Fax

61 2 9382 6191

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

Source	Title	Year of Publication	DOI
Embase	Higher or lower oxygen for delivery room resuscitation of preterm infants below 28 completed weeks gestation: A meta-analysis.	2017	https://dx.doi.org/10.1136/archdischild-2016-310435
Embase	Preterm infant outcomes after randomisation to initial resuscitation with FiO2 0.21 or 1.0.	2018	https://dx.doi.org/10.1111/jpc.13882_121
Embase	Preterm Infant Outcomes after Randomization to Initial Resuscitation with FiO2 0.21 or 1.0.	2018	https://dx.doi.org/10.1016/j.jpeds.2018.05.053

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

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Documents added automatically