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Trial registered on ANZCTR


Registration number
ACTRN12616000240448
Ethics application status
Approved
Date submitted
17/02/2016
Date registered
22/02/2016
Date last updated
19/07/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of skin-to-skin care compared with incubator care on cerebral oxygenation in preterm infants
Scientific title
Do very preterm infants less than 33 weeks gestation receiving skin-to-skin care compared with incubator care have similar (non-inferior) regional cerebral oxygenation (rcO2)?
Secondary ID [1] 288552 0
Nil
Universal Trial Number (UTN)
Trial acronym
NIRSSC-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prematurity 297660 0
Condition category
Condition code
Neurological 297847 297847 0 0
Studies of the normal brain and nervous system
Reproductive Health and Childbirth 297848 297848 0 0
Complications of newborn

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Skin-to-skin care (SSC), defined as placing a newborn prone directly onto their mother’s or father’s chest
a) duration: first 30 min of SSC will be defined as washout period and the subsequent 60 min of SSC will be used for the primary outcome. The duration of SSC will therefore last for at least 1.5 hours but might be continued as long as desired to avoid handling the preterm infants.
b) NIRS assessment: the regional cerebral oxygenation (rcO2) will be measured with a small Fore-Sight Sensor (CAS Med. Medical Systems Inc., Branford, CT, USA), which will be placed on the infant’s forehead. The sensor will be connected to the Fore-Sight device (CAS Med. Medical Systems Inc., Branford, CT, USA) and this will be connected to the monitor. Continuous data will be recorded.
c) There are three observation periods mentioned above: 1. baseline period (control) 2. intervention period, 3. post-intervention period. Each period contains a 30 min washout period and a 60 min observation period. However, SSC might be continued as long as desired to avoid handling of the preterm infants. The recordings after the 60 min
observation period will not be analysed for the primary outcome.
d) The NISC nurse will organise and supervise the SSC and the unit protocol will be used to transfer and manage the infant during the SSC. The researchers will be responsible for the placement and management of the NIRS probe. No special training will be necessary for nurses looking after babies in the study, but in-servicing about the study will be
provided.
e) The researcher will stay on the bedside during the whole study time to record handling of the infant and other possible influencing factors.
Intervention code [1] 293930 0
Treatment: Other
Comparator / control treatment
Incubator care, defined as period in the incubator in a prone position. This is standard care in the NISC
Control group
Active

Outcomes
Primary outcome [1] 297389 0
Changes (mean of the differences) in rcO2 between SSC (intervention) and incubator care (baseline) (1 hour period for each observation). This is the only primary outcome. The mean regional cerebral oxygenation (rcO2) will be measured non-invasively by near-infrared spectroscopy (NIRS) (Fore-Sight Sensor, CAS Med. Medical Systems Inc., Branford, CT, USA)
Timepoint [1] 297389 0
1 hour of skin-to-skin care (intervention period) compared to 1 hour of incubator care (baseline period).
Secondary outcome [1] 320931 0
Changes (mean of the differences) in peripheral oxygen saturation (SpO2) (oximetry, Radical7 V5, Masimo, Irvine, California, USA) between SSC (intervention) and incubator care (baseline).
Timepoint [1] 320931 0
1 hour of skin-to-skin care (intervention period) compared to 1 hour of incubator care (baseline period)
Secondary outcome [2] 320933 0
Changes (mean of the differences) in fractional tissue oxygen extraction (FTOE) equal to (SpO2 – rcO2)/SpO2 between SSC (intervention) and incubator care (baseline).
rcO2 will be assessed by NIRS (Fore-Sight Sensor, CAS Med. Medical Systems Inc., Branford, CT, USA) and SpO2 will be assessed by oximetry (Radical7 V5, Masimo, Irvine, California, USA)
Timepoint [2] 320933 0
1 hour of skin-to-skin care (intervention period) compared to 1 hour of incubator care (baseline period)
Secondary outcome [3] 320934 0
Changes (mean of the differences) in heart rate (HR) (oximetry, Radical7 V5, Masimo, Irvine, California, USA) between SSC (intervention) and incubator care (baseline).
Timepoint [3] 320934 0
1 hour of skin-to-skin care (intervention period) compared to 1 hour of incubator care (baseline period)
Secondary outcome [4] 320935 0
Changes (mean of the differences) in respiratory rate (RR) between SSC (intervention) and incubator care (baseline). The RR will be assessed by manually counting and recording every 5 minutes.
Timepoint [4] 320935 0
1 hour of skin-to-skin care (intervention period) compared to 1 hour of incubator care (baseline period)
Secondary outcome [5] 320936 0
Changes (mean of the differences) in axillary body temperature (digital clinical thermometer, Livingstone, NSW Australia) between SSC (intervention) and incubator care (baseline).
Timepoint [5] 320936 0
1 hour of skin-to-skin care (intervention period) compared to 1 hour of incubator care (baseline period)
Secondary outcome [6] 320937 0
Number of hypoxemic (SpO2 below 80%) and bradycardic episodes (bradycardia: fall in instantaneous HR by one third of the infants’ baseline HR lasting for at least 5 seconds between SSC (intervention) and incubator care (baseline). This is a composite outcome.
HR and SpO2 will be assessed by oximetry (Radical7 V5, Masimo, Irvine, California, USA) between SSC (intervention) and incubator care (baseline).
Timepoint [6] 320937 0
1 hour of skin-to-skin care (intervention) compared to 1 hour of incubator care (baseline)
Secondary outcome [7] 320938 0
Changes (mean of the differences) in rcO2 (Fore-Sight Sensor, CAS Med. Medical Systems Inc., Branford, CT, USA), between baseline and postintervention.
Timepoint [7] 320938 0
1 hour of incubator care (pre-intervention equal to baseline) compared with 1 hour of incubator care (post-intervention)
Secondary outcome [8] 320939 0
Changes (mean of the differences) in peripheral oxygen saturation (SpO2) (oximetry, Radical7 V5, Masimo, Irvine, California, USA) between baseline and post-intervention.
Timepoint [8] 320939 0
1 hour of incubator care (pre-intervention equal to baseline) compared with 1 hour of incubator care (post-intervention)
Secondary outcome [9] 320940 0
Changes (mean of the differences) in fractional tissue oxygen extraction (FTOE) equal to (SpO2 – rcO2)/SpO2 between baseline and postintervention. rcO2 will be assessed by NIRS (Fore-Sight Sensor, CAS Med. Medical Systems Inc., Branford, CT, USA) and SpO2 will be assessed by oximetry (Radical7 V5, Masimo, Irvine, California, USA)
Timepoint [9] 320940 0
1 hour of incubator care (pre-intervention = baseline) compared with 1 hour of incubator care (post-intervention).
Secondary outcome [10] 320941 0
Changes (mean of the differences) in heart rate (HR) (oximetry, Radical7 V5, Masimo, Irvine, California, USA) between baseline and postintervention.
Timepoint [10] 320941 0
1 hour of incubator care (pre-intervention equal to baseline) compared with 1 hour of incubator care (post-intervention)
Secondary outcome [11] 320944 0
Changes (mean of the differences) in respiratory rate (RR) between baseline and post-intervention. The RR will be assessed by manually counting and recording every 5
minutes.
Timepoint [11] 320944 0
1 hour of incubator care (pre-intervention equal to baseline) compared with 1 hour of incubator care (post-intervention)
Secondary outcome [12] 320945 0
Changes (mean of the differences) in axillary body temperature (digital clinical thermometer, Livingstone, NSW Australia) between baseline and post-intervention.
Timepoint [12] 320945 0
1 hour of incubator care (pre-intervention equal to baseline) compared with 1 hour of incubator care (post-intervention)
Secondary outcome [13] 320946 0
Number of hypoxemic (SpO2 below 80%) and bradycardic episodes (bradycardia: fall in instantaneous HR by one third of the infants’ baseline HR lasting for at least 5 seconds between baseline and postintervention. HR and SpO2 will be assessed by oximetry (Radical7 V5, Masimo, Irvine, California, USA) between SSC (intervention) and incubator care (baseline).
This is a composite outcome.
Timepoint [13] 320946 0
1 hour of incubator care (pre-intervention equal to baseline) compared with 1 hour of incubator care (post-intervention)
Secondary outcome [14] 320947 0
Changes (mean of the differences) in rcO2 (NIRS, Fore-Sight Sensor, CAS Med. Medical Systems Inc., Branford, CT, USA) obtained during washout period with those obtained during the main observation period for all three periods (baseline, intervention, post-intervention).
Timepoint [14] 320947 0
1 hour of skin-to-skin care (intervention) compared to 1 hour of incubator care (baseline)
Secondary outcome [15] 320948 0
Changes (mean of the differences) in rcO2 (NIRS, Fore-Sight Sensor, CAS Med. Medical Systems Inc., Branford, CT, USA) obtained during feeding periods with the rest of the observation period for all three periods (baseline, intervention, post-intervention).
Timepoint [15] 320948 0
1 hour of skin-to-skin care (intervention) compared to 1 hour of incubator care (baseline)
Secondary outcome [16] 320949 0
Changes (mean in the differences) in sleep status of infant (Quiet sleep vs. Active sleep) between SSC (intervention) and incubator care (baseline). Sleep state will be assessed using behavioural observations.
Timepoint [16] 320949 0
1 hour of skin-to-skin care (intervention period) compared to 1 hour of incubator care (baseline period).
Secondary outcome [17] 320952 0
Changes (mean in the differences) in sleep status of infant (Quiet sleep vs. Active sleep) between incubator care (baseline) and incubator care (post-intervention). Sleep state will be assessed using behavioural observations.
Timepoint [17] 320952 0
1 hour of incubator care (pre-intervention equal to baseline) compared with 1 hour of incubator care (post-intervention)

Eligibility
Key inclusion criteria
- Preterm infants gestational age (GA) at birth less than 33 weeks
- No respiratory support
- No additional oxygen requirements
- Corrected age for prematurity < 36 weeks
- Parental written consent.
- Clinically stable infants (according to medical and nursing staff).
Minimum age
No limit
Maximum age
91 Days
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Parents do not wish to have SSC
- First episode of SSC
- Respiratory support
- Infants who have:
- cerebral malformations
- severe hypoxia-ischaemia (Sarnat Stage III)
- post haemorrhage ventricular dilatation
- grade III-IV intraventricular haemorrhage
- treatment with inotropes
- umbilical catheters in situ

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
This study will be undertaken with prospective parental consent under
the guidelines of the Australian National Health and Medical Research
Council. Families of very preterm infants will
be approached by the researcher when parents/ clinical team plan to
undertake SSC within the next few days, the study explained, and
prospective consent obtained. Study protocol will be explained to the
participants (nurses and parents) and a suitable time will be arranged.
No allocation will take place.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Single group
Other design features
There will be the baseline (control) observation, the intervention and the post-intervention observation
Phase
Type of endpoint(s)
Safety
Statistical methods / analysis
Sample size and power estimates:
The outcome measure for this study is the difference in regional cerebral oxygenation between ski-to-skin and incubator care for each patient (ie the paired difference in percentage oxygenation). The required sample size is therefore dependent on the standard deviation of these paired differences.
Before we began the study the first study (NIRSCC, ACTRN: ACTRN12615000959572), we had no estimate as to the probable size of this standard deviation, so we calculated our required sample size (68 patients) based on effect size: we assumed that skin-to-skin care was 0.1 standard deviations worse than incubator care, and set a non-inferiority margin of 0.5 standard deviations. After we had recruited 15 patients, the standard deviation of the paired differences in our sample was 1.8. So, assuming that the true standard deviation of the paired differences is 2.0, the non-inferiority margin the study was powered for was 1% (ie skin-to-skin would be considered inferior if regional cerebral oxygenation was 1% less in skin-to-skin than in incubator care). We decided that this non-inferiority margin was too small, and that the smallest non-inferiority margin that would be clinically meaningful would be a 1.5% difference. We have therefore recalculated the sample size: With 40 patients, the study will have greater than 90% probability that the lower end of the 95%CI for the paired difference in oxygenation will be >-1.5%, assuming that the true difference between skin-to-skin and incubator care is -0.2%, and the standard deviation of the paired difference in oxygenation is 2.0.
We decided to use the estimated sample size of 40 patients for the NIRSSC-2 study.
Again the statistician will review the SD of the mean differences between incubator care and skin-to-skin care after studying 15 patients.

Recruitment
Recruitment status
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)
VIC
Recruitment hospital [1] 5290 0
The Royal Women's Hospital - Parkville
Recruitment postcode(s) [1] 12751 0
3052 - Parkville

Funding & Sponsors
Funding source category [1] 292908 0
Hospital
Name [1] 292908 0
Royal Women's Hospital
Address [1] 292908 0
20 Flemington Road
Parkville VIC 3052
Country [1] 292908 0
Australia
Primary sponsor type
Hospital
Name
Royal Women's hospital
Address
20 Flemington Road
Parkville VIC 3052
Country
Australia
Secondary sponsor category [1] 291665 0
None
Name [1] 291665 0
nil
Address [1] 291665 0
nil
Country [1] 291665 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294416 0
The Royal Women's Hospital
Ethics committee address [1] 294416 0
20 Flemington Road
Parkville VIC 3052
Ethics committee country [1] 294416 0
Australia
Date submitted for ethics approval [1] 294416 0
27/10/2015
Approval date [1] 294416 0
09/12/2015
Ethics approval number [1] 294416 0
Project 15/19

Summary
Brief summary
Skin-to-skin contact (SSC) has advantages for newborn babies. It increases weight gain, reduces mortality, severe infection, and length of hospital stay. There are, however, conflicting results from studies, which measured physiological parameters (heart rate, breathing frequency and oxygen saturation) of preterm babies. This uncertainty is a barrier to implementation of SSC especially in very immature preterm babies. Both too much and too little oxygen supply to the brain contributes to morbidity and mortality in very preterm babies. Regional brain oxygenation (rcO2) can now be measured by a technology called near-infrared spectroscopy (NIRS). There is a lack of knowledge about brain oxygenation during SSC. If stability in rcO2 during SSC could be demonstrated this would provide reassurance that SSC is “safe” and could be used in immature babies. The primary objective of this study is to measure rcO2 during SCC compared with measurements when the baby is being cared for in their incubator or cot. We aim to include 40 very preterm babies with a gestational age at birth less than 33 weeks. We hypothesise that rcO2 remains stable during SSC (noninferiority trial). The brain oxygen levels will not be visible to the medical and nursing staff. The primary outcome will be changes (mean of the differences) in rcO2 between SSC (intervention) and incubator care (baseline) (1 hour period for each observation). Secondary outcome will be changes (mean of the differences) in physiological parameters e.g. peripheral oxygen saturation (SpO2), fractional tissue oxygen extraction (FTOE) equal to (SpO2 – rcO2)/SpO2) heart rate (HR), and respiratory rate (RR), axillary body temperature and sleep status (quiet sleep vs. active sleep) between SSC (intervention) and incubator care (baseline), the number of hypoxemic (SpO2 less than 80%) and bradycardic episodes (bradycardia: fall in instantaneous HR by one third of the infants’ baseline HR lasting for at least 5 seconds between SSC (intervention) and incubator care (baseline), changes (mean of the differences) in rcO2, SpO2, fractional tissue oxygen extraction (FTOE) equal to (SpO2 – rcO2)/SpO2, HR, RR, number of hypoxemic and bradycardic episodes, axillary body temperature, and sleep status (quiet sleep vs. active sleep) between post intervention incubator care and pre-intervention incubator care (baseline) (1 hour period for each observation). Further sub group analysis will be changes (mean of the differences) in rcO2 obtained during washout period with those obtained during the main observation period for all three periods (baseline, intervention, postintervention) and changes in rcO2 (mean of the differences) obtained during feeding periods with the rest of the observation period for all three periods (baseline, intervention, post-intervention).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 63582 0
Dr Laila Lorenz
Address 63582 0
Newborn Research Department The Royal Women's Hospital Flemington
Road 20 3052 Parkville Melbourne, VIC
Country 63582 0
Australia
Phone 63582 0
+61-477799274
Fax 63582 0
Email 63582 0
laila.lorenz@thewomens.org.au
Contact person for public queries
Name 63583 0
Dr Laila Lorenz
Address 63583 0
Newborn Research Department The Royal Women's Hospital Flemington
Road 20 3052 Parkville Melbourne, VIC
Country 63583 0
Australia
Phone 63583 0
+61-477799274
Fax 63583 0
Email 63583 0
laila.lorenz@thewomens.org.au
Contact person for scientific queries
Name 63584 0
Dr Laila Lorenz
Address 63584 0
Newborn Research Department The Royal Women's Hospital Flemington
Road 20 3052 Parkville Melbourne, VIC
Country 63584 0
Australia
Phone 63584 0
+61-477799274
Fax 63584 0
Email 63584 0
laila.lorenz@thewomens.org.au

No information has been provided regarding IPD availability
Summary results
No Results