Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000253606
Ethics application status
Approved
Date submitted
3/03/2014
Date registered
10/03/2014
Date last updated
13/04/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
CORD CLAMPING STUDY: Early versus delayed cord clamping and its effects on infant heart rate and oxygen saturation in the first minutes after birth.
Scientific title
In newly born infants, greater or equal to 32 weeks gestation, does early cord clamping < 60s after birth versus delaying cord clamping (90 to 180s) after birth, or after breathing has established, result in less bradycardia (Heart rate (HR) <100 bpm), when HR is measured 90s after birth?
Secondary ID [1] 284184 0
none
Universal Trial Number (UTN)
U1111-1152-4622
Trial acronym
TOCC - Time of Cord Clamping Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bradycardia in the first minutes after birth 290954 0
Condition category
Condition code
Reproductive Health and Childbirth 291300 291300 0 0
Childbirth and postnatal care
Reproductive Health and Childbirth 291301 291301 0 0
Complications of newborn

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
There are three intervention groups
1. Early cord clamping group ( <60s after birth)
2. Delayed cord clamping (> 90s but less than 180s after birth)
2. Clamping the cord 10s after crying and breathing has been established
Intervention code [1] 288631 0
Other interventions
Comparator / control treatment
Early cord clamping group ( <60s after birth)
Control group
Active

Outcomes
Primary outcome [1] 291298 0
HR measured by pulse oximetry
Timepoint [1] 291298 0
90s after birth
Primary outcome [2] 291567 0
Heart rate measured by StethocloudTM (a digital microphone enabled stethoscope)
Timepoint [2] 291567 0
90s after birth
Secondary outcome [1] 306446 0
Comparison between HR in study infants compared to HR centile charts
Timepoint [1] 306446 0
The first 10 minutes after birtth
Secondary outcome [2] 306447 0
Comparison between oxygen saturation measurments in study infants compared to published centile charts for oxygen saturation measurements
Timepoint [2] 306447 0
The first 10 minutes after birth
Secondary outcome [3] 306448 0
First heart rate data available on the oximeter
Timepoint [3] 306448 0
Time for the first heart rate data to be available on the oximeter
Secondary outcome [4] 306449 0
Need for active resuscitation in the delivery room with oxygen or continuous positive airway pressure (CPAP),or positive pressure ventilation (PPV), or intubation
Timepoint [4] 306449 0
Within the first 10 minutes after birth
Secondary outcome [5] 306451 0
Any treatment of hyperbilirubinaemia (measured by serum bilirubin) with phototherapy
Timepoint [5] 306451 0
Within the first 28 days after birth
Secondary outcome [6] 306452 0
Post partum haemorrhage more than 500mls, blood loss estimated by midwife
Timepoint [6] 306452 0
Within the first 30 mins following birth of the baby.
Secondary outcome [7] 306453 0
Severe post partum haemorrhage more than 1000 mls, blood loss estimated by midwife
Timepoint [7] 306453 0
Within the first 30 mins following the birth of the baby
Secondary outcome [8] 307085 0
Time to infant's first cry after birth
Timepoint [8] 307085 0
seconds after birth
Secondary outcome [9] 307086 0
Infant Apgar score
Timepoint [9] 307086 0
one and five minutes after birth
Secondary outcome [10] 307087 0
Any true blood glucose < 2.6 mmols/L measured by blood gas machine or via laboratory
Timepoint [10] 307087 0
Within the first 48 hours after birth
Secondary outcome [11] 315699 0
Temperature per axilla measured with a digital thermometer
Timepoint [11] 315699 0
20 minutes after birth
Secondary outcome [12] 315700 0
Non-invasive blood pressure measured via the right arm with a cuff of the appropriate size and a Dinamp monitor
Timepoint [12] 315700 0
20 minutes after birth

Eligibility
Key inclusion criteria
Any infant over or equal to 32 weeks’ gestation born at RWH is eligible for inclusion in the cord clamping study unless they meet exclusion criteria
Minimum age
32 Weeks
Maximum age
42 Weeks
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
*Multiple birth
*Fetal bradycardia /fetal distress where birth is expedited with C/S or instrumental delivery
*Nuchal cord requiring division before birth of the infant
*Maternal general anaesthetic
*Placenta praevia
*Vasa praevia
*Planned lotus birth
*Planned water birth
*Known congenital anomalies necessitating early transfer to a surgical centre
*Infants >= 37 weeks gestation enrolled in the Flamingo study (possible effect of cord clamping on cord gas measurements in Flamingo study)
*Non-English speaking parents unable to provide informed consent
*Infants whose parents have elected to have their infant’s cord blood banked
*Parents with a birth plan detailing management of the third stage including timing of cord clamping and cutting

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)
Before birth (prior to second stage of labour or first incision at a caesarean section) study infants will be randomised to a treatment group according to location ( operating theatres or birthing room) and gestational age strata (32+0 to 36+6 and >= 37+0 weeks’ gestation). The sequence of randomisation concealment has been generated independently and assignment concealed in consecutively numbered sealed opaque envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Block randomisation will be used with random block sizes.
Randomisation will be blocked in 3 randomly allocated block sizes to ensure concealment of allocation.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Three intervention groups
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Data Analysis:The difference in mean heart rate between assigned groups and within assigned groups at 90s after birth will be tested with analysis of variance (ANOVA). If the heart rate data is not normally distributed the non-parametric equivalent of one-way ANOVA, the Kruskal-Wallis test will be used.
Sample size:In one of our previous studies 50 % of study infants had a HR <100 bpm at 90 s. To reduce the proportion of HR <100 bpm to 35%, with 80% power, alpha <0.05, requires 227 in each of the groups. A total of 681 infants is required. To account for post randomisation exclusions (for example an obstetric emergency or the need for neonatal resuscitation), an additional 10% will be enrolled. Thus, we will recruit 749 infants.

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Date of first participant enrolment
Anticipated
1/04/2014
Actual
1/07/2014
Date of last participant enrolment
Anticipated
1/07/2016
Actual
13/07/2015
Date of last data collection
Anticipated
Actual
Sample size
Target
749
Accrual to date
Final
27
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 1981 0
The Royal Women's Hospital - Parkville
Recruitment postcode(s) [1] 7707 0
3052 - Parkville

Funding & Sponsors
Funding source category [1] 288577 0
Government body
Name [1] 288577 0
Centre of Excellence for Newborn Medicine - National Health and Medical Research Council.
Country [1] 288577 0
Australia
Primary sponsor type
Hospital
Name
The Royal Women's Hospital
Address
Cnr Grattan Street & Flemington Road
Parkville, Victoria, 3052
Country
Australia
Secondary sponsor category [1] 287287 0
None
Name [1] 287287 0
Address [1] 287287 0
Country [1] 287287 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290440 0
The Royal Women's Hospital Research and Ethics Committee
Ethics committee address [1] 290440 0
The Royal Women's Hospital
Cnr Grattan Street and Flemington Road
Parkville, Victoria, 3052
Ethics committee country [1] 290440 0
Australia
Date submitted for ethics approval [1] 290440 0
Approval date [1] 290440 0
16/01/2014
Ethics approval number [1] 290440 0
13/44

Summary
Brief summary
The active management of the third stage of labour involves clamping and cutting the umbilical cord and application of controlled cord traction after adminstration of syntometrine, to deliver the placenta. The optimal timing of cord clamping is unknown and practice varies amongst professionals globally. Many healthy newly born infants experience bradycardia (heart rate less than 100 beats per minute) in the first few minutes. The timing of clamping the umbilical cord may influence the proportion of babies experiencing bradycardia.
The aims of this randomised controlled study are
1. To determine if delaying clamping of the cord reduces bradycardia in the first minutes after birth in near term and term infants
2. To determine if delaying clamping of the cord has an effect on the need for delivery room resuscitation
3. To determine if there is a difference in heart rate and oxygen saturation centiles in the first 10 mins after birth in three groups of infants
(i) born after early (< 60s after birth) cord clamping compared to (ii) infants born after delayed (90-180 s after birth) cord clamping or (iii) when the umbilical cord is clamped following the onset of regular respirations (10 s after accoucher determines onset of regular respirations) by the infant.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 45694 0
Dr Omar Kamlin
Address 45694 0
Newborn Research
7th Floor
The Royal Women's Hospital
Cnr Grattan street and Flemington Road
Parkville, Victoria, 3052
Country 45694 0
Australia
Phone 45694 0
+61 3 8345 3763
Fax 45694 0
Email 45694 0
[email protected]
Contact person for public queries
Name 45695 0
Dr Omar Kamlin
Address 45695 0
Newborn Research
7th Floor
The Royal Women's Hospital
Cnr Grattan street and Flemington Road
Parkville, Victoria, 3052
Country 45695 0
Australia
Phone 45695 0
+61 3 8345 3763
Fax 45695 0
Email 45695 0
[email protected]
Contact person for scientific queries
Name 45696 0
Dr Jennifer Dawson
Address 45696 0
Newborn Research
7th Floor
The Royal Women's Hospital
Cnr Grattan street and Flemington Road
Parkville, Victoria, 3052
Country 45696 0
Australia
Phone 45696 0
+61 3 8345 3763
Fax 45696 0
Email 45696 0
[email protected]

No information has been provided regarding IPD availability


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No Supporting Document Provided



Results publications and other study-related documents

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