Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000277145
Ethics application status
Approved
Date submitted
14/02/2019
Date registered
25/02/2019
Date last updated
8/10/2021
Date data sharing statement initially provided
25/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Resuscitating newborn infants with the umbilical cord intact to improve oxygen delivery to the brain- a substudy of a randomised trial
Scientific title
Cerebral Haemodynamics and Oxygenation during Physiologically-based cord clamping (CHOP) for resuscitation of term and near-term infants – a sub study of the Baby-Directed Umbilical Cord Cutting (BabyDUCC) Physiology Randomised Controlled Trial
Secondary ID [1] 297409 0
None
Universal Trial Number (UTN)
U1111-1228-5904
Trial acronym
The CHOP Study
Linked study record
ACTRN12618000621213- This record is a sub-study of this study.

Health condition
Health condition(s) or problem(s) studied:
Neonatal transition 311572 0
Neonatal resuscitation 311573 0
Birth asphyxia 311574 0
Umbilical cord clamping 311575 0
Cerebral haemodynamics 311576 0
Condition category
Condition code
Reproductive Health and Childbirth 310208 310208 0 0
Childbirth and postnatal care
Reproductive Health and Childbirth 310209 310209 0 0
Complications of newborn

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Establishment of ventilation, either via positive pressure ventilation or effective spontaneous breathing, prior to umbilical cord clamping, as detailed below.

All infants will be assessed for the need for respiratory support after birth per Australian Neonatal Resuscitation guidelines by the paediatrician in attendance at the delivery. If the infant requires respiratory support after birth, the infant will be randomised to Baby-DUCC (resuscitation prior to umbilical cord clamping) or the control arm (immediate cord clamping and the infant will be moved to the warming bed for resuscitation measures).
If the infant is vigorous and does not need resuscitation, the infant will not be randomised and umbilical cord clamping will occur at least 2 minutes after birth, oxytocin administration will occur after umbilical cord clamping. Infants must be randomised prior to 60 seconds after delivery to be included in the primary analysis. All monitoring initiated for the purpose of the study will be easily visible to the care team and can be used for evaluation of the infant.
If the non-vigorous infant is randomised to Baby-DUCC, respiratory support will be provided using a portable respiratory support system located on a mobile pole equipped with a T-Piece, oxygen blender, and suction catheter. In a vaginal delivery, the infant will be placed on a portable mattress on the end of the bed. If the end of the bed has been removed (i.e. the mother is in stirrups for an instrumental delivery) then the mattress will be placed in a portable cot and positioned between the mother’s legs. If respiratory support is indicated, positive pressure ventilation or CPAP, can be provided the respiratory support pole. A disposal colorimetric exhaled carbon dioxide detector (pedicap or neostat) will be placed between the facemask and T-Piece. Colour change indicates exhaled carbon dioxide
is greater than or equal to 15mmHg, and will be monitored by the researcher. If the infant receives PPV, umbilical cord clamping will be delayed until at least 60 seconds after colour change of the pedicap/neostat has occurred. If the infant receives CPAP only, umbilical cord clamping occurs at at least 2 minutes after delivery. The duration of respiratory support will be determined by the clinical team and will follow standard clinical practice. Oxytocin for the prevention of postpartum haemorrhage will be administered after umbilical cord clamping.

All interventions, including the provision of resuscitation, umbilical cord clamping and clinical decision making will be by the clinical team. The researcher will be responsible for the application of monitoring equipment and collection of data. The researcher will be available for medical assistance if requested by the clinical team.

Deviations from adherence to the study protocol will be documented by researcher. A video camera will be focused on the monitor to verify accuracy of the recorded data. Audio recording from the video camera or additional audio recorder will be used to verify accurately events during delivery, for example the timing of umbilical cord clamping, the time to initiate breathing, and the timing of pedicap/neostat colour change.
Intervention code [1] 313659 0
Treatment: Other
Comparator / control treatment
Immediate cord clamping if the infant requires resuscitation.

Infants not requiring resuscitation are not randomised but enter an observational arm of the study. In this study arm, all infants receive at least 2 minutes of delayed cord clamping with oxytocin administration following cord clamping. The schedule for physiological measurements will be the same as infants in the randomised arms. Infants in this non-randomised study arm will act as internal controls and enable normal ranges of the study measurements to be defined. Comparisons will be made between infants in each of the randomised study arms and infants in the non-randomised internal control group.
Control group
Active

Outcomes
Primary outcome [1] 319090 0
Mean blood pressure at 3-4 minutes after birth measured on the right arm using an automated neonatal blood pressure cuff.
Timepoint [1] 319090 0
3-4 minutes after birth
Secondary outcome [1] 366958 0
Change in regional cerebral oxygenation over time, measured using Near Infrared Spectroscopy
Timepoint [1] 366958 0
First 12 minutes after birth
Secondary outcome [2] 366959 0
Regional cerebral oxygenation measured using Near Infrared Spectroscopy
Timepoint [2] 366959 0
At 1 hour after birth
Secondary outcome [3] 380980 0
Change in regional cerebral fractional tissue oxygen extraction over time, measured using Near Infrared Spectroscopy and Pulse Oximetry
Timepoint [3] 380980 0
First 12 minutes after birth
Secondary outcome [4] 380981 0
Systolic blood pressure at 3-4 minutes after birth measured on the right arm using an automated neonatal blood pressure cuff.
Timepoint [4] 380981 0
3-4 minutes after birth
Secondary outcome [5] 380982 0
Diastolic blood pressure at 3-4 minutes after birth measured on the right arm using an automated neonatal blood pressure cuff.
Timepoint [5] 380982 0
3-4 minutes after birth
Secondary outcome [6] 380983 0
Mean blood pressure at 6-7 minutes after birth measured on the right arm using an automated neonatal blood pressure cuff.
Timepoint [6] 380983 0
6-7 minutes after birth
Secondary outcome [7] 380984 0
Systolic blood pressure at 6-7 minutes after birth measured on the right arm using an automated neonatal blood pressure cuff.
Timepoint [7] 380984 0
6-7 minutes after birth
Secondary outcome [8] 380985 0
Diastolic blood pressure at 6-7 minutes after birth measured on the right arm using an automated neonatal blood pressure cuff.
Timepoint [8] 380985 0
6-7 minutes after birth

Eligibility
Key inclusion criteria
Inclusion criteria are as per the BabyDUCC trial (ACTRN12618000621213). Infants greater than or equal to 32 weeks’ gestation, with a request for a paediatrician to attend the delivery for potential newborn distress, born at the participating centres, are eligible for inclusion. The intervention arm requires that maternal oxytocin administration will occur at between 2 and 5 minutes after delivery. Assessment of the need for early maternal oxytocin administration after delivery, and permission from the maternal care team prior to recruitment and enrolment is required.

In addition, for this sub-study the following additional inclusion criteria apply:
- Availability of additional research resources to conduct the study measurements
- antenatal consent for the measurements detailed above (blood pressure, doppler ultrasound, near infrared spectroscopy).
Minimum age
0 Hours
Maximum age
1 Hours
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria are as per the BabyDUCC trial (ACTRN12618000621213). We will not approach expecting mothers of monochorionic twins and multiples of >2, fetuses with known congenital anomalies compromising cardiorespiratory transition after birth, including congenital diaphragmatic hernia, hydrops fetalis, cyanotic congenital heart defects, and airway anomalies that may compromise the ability to provide face mask PPV.
If the maternal treatment team feels that the mother is at high risk for obstetric complications that may be exacerbated by the study intervention, and/or requires early oxytocin administration after delivery, they will not be approached for consent. Potential maternal obstetric complications that may meet criteria for exclusion from the study at the discretion of the maternal care team include abnormal placentation, suspected placental abruption, suspected uterine rupture, significant blood loss, and coagulopathy.

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)
This will be as per the BabyDUCC randomised trial (ACTRN12618000621213). The randomisation tables will be incorporated into the REDCap randomisation tool (hosted by the Murdoch Children’s Research Institute). A weblink to the tool will be accessed via a mobile device at delivery and enables randomisation to be completed within seconds of the the clinical team's decision to commence resuscitation. This decision must be made within 60 seconds of delivery of the infant.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
This will be as per the BabyDUCC randomised trial (ACTRN12618000621213). Computer-generated, random block sizes will be used with stratification. Infants will be stratified by gestational age (32-35 weeks, or greater than or equal to 36 weeks at birth). Infants greater than or equal to 36 weeks gestation at birth will also be stratified into non-emergent and emergent deliveries. Emergent deliveries include emergent caesarean sections (“code green”) and vaginal instrumental deliveries.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features

Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Infant characteristics will be presented as numbers and proportions for categorical variables, means and standard deviations for normally distributed continuous variables, and medians and interquartile ranges for variables with skewed distribution.

Cerebral blood flow values will only be measured with consistent doppler waveforms in the ultrasound recording. Cerebral oxygenation values be used if the NIRS monitor shows good quality signal on the video recording.

For the primary outcome, the mean blood pressure will be compared between intervention groups using an independent t-test. Imbalances in the randomised strata will be adjusted for using linear regression. Continuous cerebral oxygenation in the first 10 minutes after birth will be collected, and trends compared between groups using two-way mixed ANOVA or linear mixed methods regression depending on completeness of data. Continuous variables will be compared using an independent samples t-test if normally distributed and a 2-sided Mann-Whitney U test for non-normally distributed data. Categorical variables will be compared using the Fisher’s exact test. Statistical significance will be considered at p<0.05. Subgroup analyses for each outcome are planned for individual strata.

Comparison of each randomised arm and with the non-randomised internal control group for each of the study measures: right arm blood pressure, cerebral blood flow and cerebral oxygenation

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
27/02/2019
Actual
5/03/2019
Date of last participant enrolment
Anticipated
20/08/2020
Actual
12/04/2021
Date of last data collection
Anticipated
20/08/2020
Actual
20/04/2021
Sample size
Target
50
Accrual to date
Final
55
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 25697 0
3052 - Parkville

Funding & Sponsors
Funding source category [1] 301979 0
Government body
Name [1] 301979 0
National Health And Medical Research Council Program Grant
Country [1] 301979 0
Australia
Primary sponsor type
Hospital
Name
The Royal Women's Hospital
Address
20 Flemington Rd, Parkville VIC 3052
Country
Australia
Secondary sponsor category [1] 301756 0
None
Name [1] 301756 0
Address [1] 301756 0
Country [1] 301756 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302658 0
The Royal Women's Hospital Human Research and Ethics Committee
Ethics committee address [1] 302658 0
Ethics committee country [1] 302658 0
Australia
Date submitted for ethics approval [1] 302658 0
04/09/2018
Approval date [1] 302658 0
17/10/2018
Ethics approval number [1] 302658 0
17/19

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 90962 0
Dr Shiraz Badurdeen
Address 90962 0
Newborn Research Centre, Level 7, Royal Women's Hospital, 20 Flemington Rd, Parkville VIC 3052
Country 90962 0
Australia
Phone 90962 0
+61 3 8345 3763
Fax 90962 0
Email 90962 0
[email protected]
Contact person for public queries
Name 90963 0
Shiraz Badurdeen
Address 90963 0
Newborn Research Centre, Level 7, Royal Women's Hospital, 20 Flemington Rd, Parkville VIC 3052
Country 90963 0
Australia
Phone 90963 0
+61 3 8345 3763
Fax 90963 0
Email 90963 0
[email protected]
Contact person for scientific queries
Name 90964 0
Shiraz Badurdeen
Address 90964 0
Newborn Research Centre, Level 7, Royal Women's Hospital, 20 Flemington Rd, Parkville VIC 3052
Country 90964 0
Australia
Phone 90964 0
+61 3 8345 3763
Fax 90964 0
Email 90964 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data collected during the trial after de-identification, subject to Ethics review
When will data be available (start and end dates)?
Immediately following publication, no end date determined
Available to whom?
Researchers who provide a methodologically sound proposal, judged on a case-by-case basis
Available for what types of analyses?
Only to achieve the aims in the approved proposal
How or where can data be obtained?
Access will be via direct electronic communication and will be subject to approvals by Principal Investigators, Local Institutional and Ethics review.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
1361Ethical approval    376976-(Uploaded-14-02-2019-13-58-08)-Study-related document.pdf



Results publications and other study-related documents

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

Documents added automatically
No additional documents have been identified.