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Trial registered on ANZCTR

Registration number

ACTRN12615000959572

Ethics application status

Approved

Date submitted

24/08/2015

Date registered

14/09/2015

Date last updated

11/08/2016

Type of registration

Retrospectively registered

Titles & IDs

Public title

Effect of skin-to-skin care compared with incubator care on cerebral oxygenation in preterm infants on respiratory support

Scientific title

Do very preterm infants less than 33 weeks gestation on respiratory support receiving skin-to-skin care compared with incubator care have similar (non-inferior) regional cerebral oxygenation (rcO2)?

Secondary ID [1]

Nil

Universal Trial Number (UTN)

Trial acronym

NIRSSC

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Prematurity

Condition category

Condition code

Neurological

Studies of the normal brain and nervous system

Reproductive Health and Childbirth

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 underneath a CPAP hat. 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) respiratory support: one of the inclusion criteria is that the infants need to receive some kind of respiratory support, either CPAP, High-Flow nasal cannula or ventilation via an endotracheal tube. All infants will stay on the same respiratory support during the three mentioned study periods: the baseline period (incubator care before intervention), intervention period (SSC) and post intervention period (incubator care after SSC).
d) 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. e) 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. f) 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]

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]

Changes (mean of the differences) in rcO2 between SSC (intervention) and incubator care (baseline) (1 hour period for each observation). This is the only prim 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]

1 hour of skin-to-skin care (intervention period) compared to 1 hour of incubator care (baseline period).

Secondary outcome [1]

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]

1 hour of skin-to-skin care (intervention period) compared to 1 hour of incubator care (baseline period)

Secondary outcome [2]

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]

1 hour of skin-to-skin care (intervention period) compared to 1 hour of incubator care (baseline period)

Secondary outcome [3]

Changes (mean of the differences) in inspired oxygen (FiO2). The FiO2 is assessed by a device called Teledyne oxygen analyser (Teledyne Analytical Instruments, California, USA), which will be inserted into the inspiratory limb of the ventilation device inspired. We will compare FiO2 between SSC (intervention) and incubator care (baseline).

Timepoint [3]

1 hour of skin-to-skin care (intervention period) compared to 1 hour of incubator care (baseline period)

Secondary outcome [4]

Changes (mean of the differences) in heart rate (HR) (oximetry, Radical7 V5, Masimo, Irvine, California, USA) between SSC (intervention) and incubator care (baseline).

Timepoint [4]

1 hour of skin-to-skin care (intervention period) compared to 1 hour of incubator care (baseline period)

Secondary outcome [5]

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 [5]

1 hour of skin-to-skin care (intervention period) compared to 1 hour of incubator care (baseline period)

Secondary outcome [6]

Changes (mean of the differences) in axillary body temperature (digital clinical thermometer, Livingstone, NSW Australia) between SSC (intervention) and incubator care (baseline).

Timepoint [6]

1 hour of skin-to-skin care (intervention period) compared to 1 hour of incubator care (baseline period)

Secondary outcome [7]

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 [7]

1 hour of skin-to-skin care (intervention) compared to 1 hour of incubator care (baseline)

Secondary outcome [8]

Changes (mean of the differences) in rcO2 (Fore-Sight Sensor, CAS Med. Medical Systems Inc., Branford, CT, USA), between baseline and post-intervention.

Timepoint [8]

1 hour of incubator care (pre-intervention equal to baseline) compared with 1 hour of incubator care (post-intervention)

Secondary outcome [9]

Changes (mean of the differences) in peripheral oxygen saturation (SpO2) (oximetry, Radical7 V5, Masimo, Irvine, California, USA) between baseline and post-intervention.

Timepoint [9]

1 hour of incubator care (pre-intervention equal to baseline) compared with 1 hour of incubator care (post-intervention)

Secondary outcome [10]

Changes (mean of the differences) in fractional tissue oxygen extraction (FTOE) equal to (SpO2 – rcO2)/SpO2 between baseline and post-intervention.

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 [10]

1 hour of incubator care (pre-intervention = baseline) compared with 1 hour of incubator care (post-intervention).

Secondary outcome [11]

Changes (mean of the differences) in inspired oxygen (FiO2) between baseline and post-intervention.

The FiO2 is assessed by a device called Teledyne oxygen analyser (Teledyne Analytical Instruments, California, USA), which will be inserted into the inspiratory limb of the ventilation device inspired.

Timepoint [11]

1 hour of incubator care (pre-intervention equal to baseline) compared with 1 hour of incubator care (post-intervention)

Secondary outcome [12]

Changes (mean of the differences) in heart rate (HR) (oximetry, Radical7 V5, Masimo, Irvine, California, USA) between baseline and post-intervention.

Timepoint [12]

1 hour of incubator care (pre-intervention equal to baseline) compared with 1 hour of incubator care (post-intervention)

Secondary outcome [13]

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 [13]

1 hour of incubator care (pre-intervention equal to baseline) compared with 1 hour of incubator care (post-intervention)

Secondary outcome [14]

Changes (mean of the differences) in axillary body temperature (digital clinical thermometer, Livingstone, NSW Australia) between baseline and post-intervention.

Timepoint [14]

1 hour of incubator care (pre-intervention equal to baseline) compared with 1 hour of incubator care (post-intervention)

Secondary outcome [15]

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 post-intervention.

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 [15]

1 hour of incubator care (pre-intervention equal to baseline) compared with 1 hour of incubator care (post-intervention)

Secondary outcome [16]

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 [16]

1 hour of skin-to-skin care (intervention) compared to 1 hour of incubator care (baseline)

Secondary outcome [17]

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 [17]

1 hour of skin-to-skin care (intervention) compared to 1 hour of incubator care (baseline)

Secondary outcome [18]

Changes (mean of the differences) in rcO2 (NIRS, Fore-Sight Sensor, CAS Med. Medical Systems Inc., Branford, CT, USA) between baseline and intervention period of ventilated infants with those from infants on CPAP and High-Flow nasal cannula

Timepoint [18]

1 hour of skin-to-skin care (intervention) compared to 1 hour of incubator care (baseline)

Eligibility

Key inclusion criteria

- Preterm infants gestational age (GA) at birth less than 33 weeks receiving respiratory support (CPAP, High-Flow nasal cannula or ventilation via an endotracheal tube).
- Parental written consent.
- Clinically stable infants (according to medical and nursing staff).

Minimum age

1 Days

Maximum age

3 Months

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

- Parents do not wish to have SSC
- First episode of SSC
- 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 requiring respiratory support (CPAP, High-Flow nasal cannula or ventilation via endotracheal tube) 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)

N/A

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

Not Applicable

Type of endpoint/s

Safety

Statistical methods / analysis

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, 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.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

Actual

8/09/2015

Date of last participant enrolment

Anticipated

Actual

20/04/2016

Date of last data collection

Anticipated

Actual

20/04/2016

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

The Royal Women's Hospital - Parkville

Recruitment postcode(s) [1]

3052 - Parkville

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

The Royal Women's Hospital

Address [1]

20 Flemington Road
Parkville VIC 3052

Country [1]

Australia

Primary sponsor type

Hospital

Name

The Royal Women's Hospital Melbourne

Address

20 Flemington Road
Parkville VIC 3052

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

The Royal Womens Hospital Melbourne

Ethics committee address [1]

20 Flemington Rd
Parkville VIC 3052

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

05/08/2015

Approval date [1]

25/08/2015

Ethics approval number [1]

Project 15/19

Summary

Brief summary

Skin-to-skin contact (SSC) is defined as placing a baby prone directly onto their mother’s or father’s chest. 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. Some studies showed an increase in oxygen desaturations and a decrease in regular breathing, others however a decrease in oxygen desaturations during SSC. 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 and there are no data in very preterm babies during their first days of life. If stability in rcO2 during SSC could be demonstrated this would provide reassurance that SSC is “safe” and could be used in immature babies who are receiving breathing assistance. 

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 68 very preterm babies with a gestational age at birth less than 33 weeks receiving breathing assistance. We hypothesise that rcO2 remains stable during SSC (non-inferiority 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 and ventilation parameters e.g. peripheral oxygen saturation (SpO2), fractional tissue oxygen extraction (FTOE) equal to (SpO2 – rcO2)/SpO2, inspired oxygen (FiO2), heart rate (HR), and respiratory rate (RR), axillary body temperature 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, FiO2, number of hypoxemic and bradycardic episodes, axillary body temperature 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, post-intervention), 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), changes in rcO2 (mean of the differences) between baseline and intervention period of ventilated infants with those from infants on CPAP and High-Flow nasal cannula.

Trial website

NA

Trial related presentations / publications

NA

Public notes

NA

Contacts

Principal investigator

Name

Dr Laila Lorenz

Address

Newborn Research Department
The Royal Women's Hospital
Flemington Road 20
3052 Parkville
Melbourne, VIC

Country

Australia

Phone

+61-477799274

Fax

[email protected]

Contact person for public queries

Name

Laila Lorenz

Address

Dr. Laila Lorenz
Newborn Research Department
The Royal Women's Hospital
Flemington Road 20
3052 Parkville
Melbourne, VIC

Country

Australia

Phone

+61-477799274

Fax

[email protected]

Contact person for scientific queries

Name

Laila Lorenz

Address

Newborn Research Department
The Royal Women's Hospital
Flemington Road 20
3052 Parkville
Melbourne, VIC

Country

Australia

Phone

+61-477799274

Fax

[email protected]

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

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Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Skin-to-skin care in preterm infants receiving respiratory support does not lead to physiological instability.	2017	https://dx.doi.org/10.1136/archdischild-2016-311752

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

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