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Trial registered on ANZCTR


Registration number
ACTRN12618000879268
Ethics application status
Approved
Date submitted
24/04/2018
Date registered
25/05/2018
Date last updated
18/06/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Targeted Oxygenation in the Respiratory care of Premature Infants at Delivery: Effects on Outcome (TORPIDO 30/60)
Scientific title
Lower or higher initial oxygen concentration with Targeted Oxygen saturation in Respiratory care of premature Infants at Delivery: effects on Outcome (TORPIDO 30/60)
Secondary ID [1] 294612 0
Nil
Universal Trial Number (UTN)
Trial acronym
Torpido 30/60
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Premature infants requiring resuscitation at birth 307445 0
Condition category
Condition code
Reproductive Health and Childbirth 306530 306530 0 0
Complications of newborn

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
At delivery, a CPAP mask will be applied by the caregiver (e.g. midwife, neonatal clinician, obstetrician, anaesthetist), and initial FiO2 level will be set to 0.6. Using a pulse oximeter, FiO2 will be adjusted as required to achieve target SpO2 (80-85% at 5 min and 85-95% at 10 min and thereafter), until admission to the NICU.
Intervention code [1] 300919 0
Treatment: Drugs
Intervention code [2] 301076 0
Treatment: Devices
Comparator / control treatment
At delivery, a CPAP mask will be applied by the caregiver (e.g. midwife, neonatal clinician, obstetrician, anaesthetist), and initial FiO2 level will be set to 0.3. Using a pulse oximeter, FiO2 will be adjusted as required to achieve target SpO2 (80-85% at 5 min and 85-95% at 10 min and thereafter).
Control group
Dose comparison

Outcomes
Primary outcome [1] 305538 0
The composite primary outcome comprises survival free from major brain injury (assessed by routine ultrasound or other imaging and/or clinical assessment). Brain injury is defined as periventricular haemorrhage (on either side of the head) seen on ultrasound with grade 1-4, or the presence by ultrasound after 14 days of any of the following: echodense
intraparenchymal lesions, periventricular leukomalacia (PVL) or porencephalic cysts
Timepoint [1] 305538 0
To 36 weeks gestation
Secondary outcome [1] 345663 0
All-cause mortality (from hospital records)
Timepoint [1] 345663 0
Death occurring on any day between birth and discharge home.
Secondary outcome [2] 345664 0
Major brain injury from any imaging performed before discharge home. Brain injury is defined as periventricular haemorrhage (on either side of the head) seen on ultrasound with grade 1-4, or the presence by ultrasound after 14 days of any of the following: echodense intraparenchymal lesions, periventricular leukomalacia (PVL) or porencephalic cysts
Timepoint [2] 345664 0
From any imaging performed before discharge home.
Secondary outcome [3] 346309 0
Tertiary Outcome (Hypothesis Generating) - Oxygen saturation (SpO2) will be monitored using a pulse oximeter until admission to NICU
Timepoint [3] 346309 0
From birth until admission to NICU
Secondary outcome [4] 346310 0
Tertiary Outcome (Hypothesis Generating) - Measured (by pulse oximeter) in 1 minute increments for the first 10 minutes of life and every 5 minutes thereafter until admission to NICU, the time it takes to reach SpO2 greater or equal to 80%
Timepoint [4] 346310 0
From birth until SpO2 reaches 80%
Secondary outcome [5] 346311 0
Tertiary Outcome (Hypothesis Generating) - Heart rate at each minute for the first 10 minutes after birth and then every 5 minutes until admission to NICU will be taken from hospital records.
Timepoint [5] 346311 0
From birth until admission to NICU
Secondary outcome [6] 346312 0
Tertiary Outcome (Hypothesis Generating) - Endotracheal Intubation in delivery suite required due to depressed respiratory effort (taken from hospital records).
Timepoint [6] 346312 0
From birth until admission to NICU
Secondary outcome [7] 346313 0
Tertiary Outcome (Hypothesis Generating) - Apgar scores (a summary of the health of the newbown) at 1 and 5 minutes
Timepoint [7] 346313 0
At 1 and 5 minutes of life
Secondary outcome [8] 346314 0
Tertiary Outcome (Hypothesis Generating) - Number of infants with severe periventricular haemorrhage from any imaging performed before discharge home.
Timepoint [8] 346314 0
From birth until discharge home
Secondary outcome [9] 346315 0
Tertiary Outcome (Hypothesis Generating) - Number of infants with Broncho-pulmonary dysplasia (BPD) defined as requirement for supplemental oxygen or respiratory support survival to 36 weeks, collected from hospital records.
Timepoint [9] 346315 0
36 weeks gestation.
Secondary outcome [10] 346316 0
Tertiary Outcome (Hypothesis Generating) - Number of infants with severe retinopathy of prematurity (ROP) as assessed by an ophthalmologist in the neonatal unit.
Timepoint [10] 346316 0
From birth until discharge home
Secondary outcome [11] 346317 0
Tertiary Outcome (Hypothesis Generating) - Number of infants with necrotising enterocolitis (NEC) confirmed with radiolographs, associated with surgery or death.
Timepoint [11] 346317 0
From birth until discharge home
Secondary outcome [12] 346318 0
Tertiary Outcome (Hypothesis Generating) - Number of infants with late onset sepsis will be collected from hospital records.
Timepoint [12] 346318 0
From 48 hours of life until discharge home
Secondary outcome [13] 346319 0
Tertiary Outcome (Hypothesis Generating) - Number of infants with Patent ductus arteriosus (PDA) will be collected from hospital records.
Timepoint [13] 346319 0
From birth until discharge home
Secondary outcome [14] 346320 0
Tertiary Outcome (Hypothesis Generating) - Duration of hospital stay defined as the number of days from admission to final discharge home (taken from hospital records).
Timepoint [14] 346320 0
From birth until discharge home
Secondary outcome [15] 346321 0
Tertiary Outcome (Hypothesis Generating) - Survival without major disability at 2-3 years corrected for gestation. Disability will be assessed by one or more of the following assessments:
a) The Bayley Scales of Infant Development (BSID III);
b) The Ages and Stages Questionnaire (ASQ)
c) Short Health Status Questionnaire (SHQ)
The ASQ and SHQ will be collected for all participants, and the BSID will be collected where routinely done.
Timepoint [15] 346321 0
at 24-36 months corrected age.

Eligibility
Key inclusion criteria
Premature infants born from 23/0 to 28/6 weeks gestation
Minimum age
23 Weeks
Maximum age
29 Weeks
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Any known major cardiopulmonary abnormalities that could affect oxygenation or congenital malformations that could affect neuro-developmental outcome or survival

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)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Treatment allocation will be stratified by study site, gestation and multiplicity.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis
A trial of 735 infants per arm (1470 total sample size) provides 85% power, with a 2 sided 5% significance level, to detect an absolute risk difference of 32% versus 24% (i.e. 25% a relative risk reduction) in the primary endpoint (brain injury free survival to 36 weeks) whilst allowing for 10% non-adherence to assigned protocol treatment. Multiple babies from the same birth will be randomised together and an intra-cluster correlation of 0.3 and an average cluster size of 1.15 is assumed.
The sample size is based on current and conservative assumptions about event rates and compliance. These parameters will be reviewed at the interim analysis and sample size will be adjusted if required.

A detailed statistical analysis plan will be prepared. All randomised subjects will be eligible for inclusion in the full analysis set in accordance with the intention-to-treat analysis principle. Comparisons between randomised groups that take stratification factors into account will be undertaken using tests for categorical variables and linear models for continuous variables. Sensitivity of results to adjustment for other covariates and possible clustering between multiples will be explored. Subgroup analyses will be specified in the statistical analysis plan.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,VIC
Recruitment outside Australia
Country [1] 10290 0
India
State/province [1] 10290 0
Bangalore
Country [2] 10291 0
Malaysia
State/province [2] 10291 0
Kuala Lumpur
Country [3] 10292 0
Singapore
State/province [3] 10292 0
Bukit Timah

Funding & Sponsors
Funding source category [1] 299229 0
Government body
Name [1] 299229 0
National Health and Medical Research Council
Address [1] 299229 0
GPO Box 1421
Canberra ACT 2601
Country [1] 299229 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
The University of Sydney
NSW 2006
Country
Australia
Secondary sponsor category [1] 298501 0
None
Name [1] 298501 0
Address [1] 298501 0
Country [1] 298501 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300154 0
Hunter New England Local Health Distritct
Ethics committee address [1] 300154 0
Lookout Road
New Lambton NSW 2305
Ethics committee country [1] 300154 0
Australia
Date submitted for ethics approval [1] 300154 0
28/11/2017
Approval date [1] 300154 0
12/06/2018
Ethics approval number [1] 300154 0
17/12/13/3.03

Summary
Brief summary
Premature infants usually need extra oxygen after birth because their lungs are not fully developed. However, their bodies do not yet have the ability to balance the stress that receiving that oxygen can cause. Oxygen is necessary for life, but both too much or too little can damage eyes, lungs, brain and other important organs of newborn babies.

This study will compare outcomes of 1470 preterm infants up to 28/6 weeks gestation who have had respiratory care in the delivery room with (A) Initial FiO2 0.6 versus (B) Initial FiO2 0.3, followed by common SpO2 targeting until admission to NICU.
FiO2, SpO2, and heart rate are recorded each minute from delivery of the child’s body for 10 minutes, then every 5 minutes until admission to NICU. Routine assessments are collected at baseline, 36 weeks, discharge and at 2 years corrected for gestation. Additionally a parent-completed developmental questionnaire is also collected at 2 years corrected for gestation.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 51254 0
Dr Ju-Lee Oei
Address 51254 0
Neonatal Intensive Care Unit
Royal Hospital for Women Randwick, NSW 2031
Country 51254 0
Australia
Phone 51254 0
+61 2 9382 6152
Fax 51254 0
Email 51254 0
j.oei@unsw.edu.au
Contact person for public queries
Name 51255 0
Ms Rebecca Brown
Address 51255 0
c/o TORPIDO30/60 Coordinator
Locked Bag 77
Camperdown NSW 1450
Country 51255 0
Australia
Phone 51255 0
+61 2 9562 5000
Fax 51255 0
Email 51255 0
torpido2@ctc.usyd.edu.au
Contact person for scientific queries
Name 51256 0
Dr Ju-Lee Oei
Address 51256 0
Neonatal Intensive Care Unit
Royal Hospital for Women Randwick, NSW 2031
Country 51256 0
Australia
Phone 51256 0
+61 2 9382 6152
Fax 51256 0
Email 51256 0
j.oei@unsw.edu.au

No data has been provided for results reporting
Summary results
Not applicable