Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615000174583
Ethics application status
Approved
Date submitted
11/02/2015
Date registered
23/02/2015
Date last updated
30/07/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Measuring the increase in exhaled carbon dioxide in spontaneously breathing infants at birth, the RISE study
Scientific title
Measurement of exhaled carbon dioxide, tidal volume, heart rate, and saturation of peripheral oxygen in infants born >34 6/7 weeks gestation not expected to require respiratory support at birth
Secondary ID [1] 286151 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neonatal resuscitation 294157 0
Lung aeration at birth 294159 0
Condition category
Condition code
Reproductive Health and Childbirth 294485 294485 0 0
Childbirth and postnatal care
Reproductive Health and Childbirth 294486 294486 0 0
Complications of newborn
Respiratory 294535 294535 0 0
Normal development and function of the respiratory system

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This is a prospective, observational study of spontaneously breathing term and late preterm infants in the delivery room. The primary outcome will be the measured exhaled carbon dioxide levels in the first ten minutes of life.

A combined neonatal CO2/Flow sensor (Neonatal CO2 Flow Sensor, Phillips Healthcare, Massachusetts, USA) will be attached to a face mask (Laerdal round mask, Laerdal, Stavanger, Norway or Neonatal Resuscitation Masks, Fisher&Paykel, Auckland, New Zealand). Immediately after birth, a face mask will be placed over the mouth and the nose. Infants will breathe through the mask.

The NM3 Respiratory Profile Monitor (Phillips Healthcare, Massachusetts, USA). consists of a combined CO2/Flow sensor which measures exhaled carbon dioxide with an infrared light beam at different wavelengths in order to precisely determine gas concentrations in the expired breaths. In addition, the monitor can record pulse and SpO2 via pulse oximetry, with a 2 second averaging time. The respiratory gas measurements are obtained by continuously measuring the infrared light absorption in gas flow through an adapter in the breathing circuit. Gas flow, tidal volume, respiratory rate and airway pressures are measured with a flow sensor. The dead space of the CO2/Flow neonatal sensor is less than 1 mL according to the manufacturer and unlikely to interfere with breathing.

We plan to obtain the measurements immediately after the baby is delivered and continue whilst the baby is lying on the mother’s chest. The purpose of the study is to measure exhaled carbon dioxide during the transition of a healthy newborn, starting with the baby’s first breath. The natural transition of the healthy newborn includes bonding with the mother after birth. To minimize interference with the normal monitoring and stabilization of preterm and term infants after birth, we will record respiratory measurements for the first 60 seconds of life, then record 10-20 breaths every 1 minute for the first ten minutes of life, at 1-2 hours of life, and at 12-72 hours of life.

The intermittent application of the facemask during the first 10 minutes of life will reduce the small risk of rebreathing carbon dioxide in the circuit’s dead space and will allow for a more natural neonatal transition. During data collection, breaths will be counted if the investigator feels that there is a proper mask seal and leak is minimal. During the study, if there are any signs of respiratory compromise, the study will be abandoned and ventilatory support given according to the Australian Neonatal Resuscitation guidelines.

After a vaginal delivery, data will be collected whilst the baby is on the mother’s chest. If the baby cannot be held by the mother (or other family member), the baby can be positioned close to the mother and placed on a dedicated research trolley with a warming mattress during data collection.

In the event of a caesarian section delivery, we will also collect data immediately after delivery. One of the researchers will scrub and don sterile gown and gloves and stand next to the delivering consultant. A dedicated research trolley with a warming mattress and sterile drapes will be placed close to the surgical field. A plastic sterile sheathing will be placed over the flow sensor tubes and wires. Two holes will be cut into the sheath and secured with sterile ties, one for a sterile mask to connect to the flow sensor and one for the distal end of the flow sensor. If the obstetric team feels that we are interfering with patient care, the study will be abandoned.

After the baby is placed onto the research trolley with a warming mattress and moved out of the sterile field, a pulse oximetry sensor will be placed on the infant’s right hand or wrist. Once the baby is out of the sterile field, the process of data collection after a caesarean delivery will be the same as for a vaginal delivery. The study should not preclude skin to skin contact of babies with their mothers after a caesarean delivery in the first ten minutes of life. The data acquisition system that will be used for this study is portable and will be housed on a research trolley with a warming mattress that can move with the baby from the sterile field to the resuscitation bed for evaluation and then to the head of the bed so that the baby can bond with the mother. The natural transition of the healthy newborn includes bonding with the mother after birth. Our goal is to minimize interference with this process.

The pulse oximeter will record continuously for the first 10 minutes of life, then the sensor will be removed. We will record the baby’s temperature at 10-12 minutes of life. The pulse oximeter will be reapplied at the 1-2 hour and 12-72 hour recordings.

We aim to record the exact timing of several events that occur in the first 2 minutes after the birth of the neonate, including the time the facemask is applied, the time the cord is clamped, the time the baby first breaths/cries, and the time that the pulse oximetry sensor is placed on the baby’s right wrist. After some trial and error recording events during routine deliveries, we feel that we will achieve a high fidelity accounting of these events after birth by making a de-identified audio recording of the investigator dictating the sequence of events into an audio recorder (an iphone placed in the investigators chest pocket). Immediately after the delivery, we will record the timing of events onto a patient data form and erase the audio recording. If available, we will also record the umbilical arterial cord blood gas for analysis.

The signals of airway flow, tidal volumes, airway pressure, breathing pattern, exhaled carbon dioxide, heart rate, and SpO2 will be converted from analog to digital signal and recorded at 100Hz using a custom built software program which presents the data in graphical and table form. Measurements recorded will be analyzed using Stata Software (StataCorp, College Station, Texas, USA) for statistical analysis.

We plan to review the data collected after enrolling 10, 20, and 50 babies. The purpose will be to review patient safety and efficacy of data collection. Specifically, we will monitor the baby’s temperature at 10-12 minutes, the risk of breaking the sterile field in caesarian sections, the potential of interfering with patient care, and need for resuscitation (apart from routine drying and stimulation).

The measurements obtained from this cohort of babies constitutes an observational study. This data will provide valuable information on exhaled carbon dioxide in the first minutes after birth.
Intervention code [1] 291154 0
Not applicable
Comparator / control treatment
The primary outcome for this study will be the average ECO2 levels obtained every minute for the first ten minutes of life, than once at 1-2 hours of life and at 12-72 hours of life.

We will compare the exhaled carbon dioxide at 12-72 hours to the exhaled carbon dioxide measured during the first ten minutes of life and at 1-2 hours of life. For statistical analysis, each subject will serve as his or her own control.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 294264 0
The primary outcome for this study will be measuring the exhaled carbon dioxide levels using the NM3 Respiratory Profile Monitor.
Timepoint [1] 294264 0
Exhaled carbon dioxide levels will be measured every minute for the first ten minutes of life, than once at 1-2 hours of life and once at 12-72 hours of life.
Secondary outcome [1] 312897 0
The change in exhaled tidal volume (TV) from birth using the NM3 Respiratory Profile Monitor.
Timepoint [1] 312897 0
Exhaled carbon dioxide measurements will be made continuously during first minute of life, then for 20 seconds every minute of life from 2-10 minutes, then for 20 seconds at 1-2 hours, and again for 20 seconds at 12-72 hours when babies without respiratory distress would be expected to have completed cardiopulmonary transition. A pulse oximetry sensor will be placed on the baby's right wrist and record continuously from birth to 10 minutes of life, then be removed. The pulse oximetry sensor will be reapplied for 1-2 minutes of continuous monitoring at 1-2 hours of life and at 12-72 hours of life at the same time that exhaled carbon dioxide measurements at being recorded.
Secondary outcome [2] 312898 0
The change in saturation of peripheral oxygenation (SpO2) from birth using the NM3 monitor.
Timepoint [2] 312898 0
Exhaled carbon dioxide measurements will be made continuously during first minute of life, then for 20 seconds every minute of life from 2-10 minutes, then for 20 seconds at 1-2 hours, and again for 20 seconds at 12-72 hours when babies without respiratory distress would be expected to have completed cardiopulmonary transition. A pulse oximetry sensor will be placed on the baby's right wrist and record continuously from birth to 10 minutes of life, then be removed. The pulse oximetry sensor will be reapplied for 1-2 minutes of continuous monitoring at 1-2 hours of life and at 12-72 hours of life at the same time that exhaled carbon dioxide measurements at being recorded.
Secondary outcome [3] 312899 0
The change in ECO2 from birth to the change in heart rate (HR) from birth using the NM3 monitor.
Timepoint [3] 312899 0
Exhaled carbon dioxide measurements will be made continuously during first minute of life, then for 20 seconds every minute of life from 2-10 minutes, then for 20 seconds at 1-2 hours, and again for 20 seconds at 12-72 hours when babies without respiratory distress would be expected to have completed cardiopulmonary transition. A pulse oximetry sensor will be placed on the baby's right wrist and record continuously from birth to 10 minutes of life, then be removed. The pulse oximetry sensor will be reapplied for 1-2 minutes of continuous monitoring at 1-2 hours of life and at 12-72 hours of life at the same time that exhaled carbon dioxide measurements at being recorded.
Secondary outcome [4] 312900 0
The change in exhaled carbon dioxide in the first minutes of life comparing different timing of umbilical cord clamping. The timing of the umbilical cord clamping will be noted by the investigator dictating the timing of the event using an audio recorder placed in the investigators shirt pocket.
Timepoint [4] 312900 0
Exhaled carbon dioxide measurements will be made continuously during first minute of life, then for 20 seconds every minute of life from 2-10 minutes, then for 20 seconds at 1-2 hours, and again for 20 seconds at 12-72 hours when babies without respiratory distress would be expected to have completed cardiopulmonary transition. A pulse oximetry sensor will be placed on the baby's right wrist and record continuously from birth to 10 minutes of life, then be removed. The pulse oximetry sensor will be reapplied for 1-2 minutes of continuous monitoring at 1-2 hours of life and at 12-72 hours of life at the same time that exhaled carbon dioxide measurements at being recorded.
Secondary outcome [5] 312901 0
Investigate if the change in ECO2 in the first minutes of life is affected by the timing of the baby’s first cry. The timing of the event will be noted by the investigator dictating the timing of the event using an audio recorder placed in the investigators shirt pocket.
Timepoint [5] 312901 0
Exhaled carbon dioxide measurements will be made continuously during first minute of life, then for 20 seconds every minute of life from 2-10 minutes, then for 20 seconds at 1-2 hours, and again for 20 seconds at 12-72 hours when babies without respiratory distress would be expected to have completed cardiopulmonary transition. A pulse oximetry sensor will be placed on the baby's right wrist and record continuously from birth to 10 minutes of life, then be removed. The pulse oximetry sensor will be reapplied for 1-2 minutes of continuous monitoring at 1-2 hours of life and at 12-72 hours of life at the same time that exhaled carbon dioxide measurements at being recorded.

Eligibility
Key inclusion criteria
All inborn infants, term and preterm born at 35 weeks or later gestational age, who are not expected to require respiratory support at birth, are eligible for this study.
Minimum age
No limit
Maximum age
0 Hours
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Infants will be excluded from analysis if they have a congenital abnormality or condition that might have an adverse effect on breathing or respiratory drive including: infants born to mothers receiving general anesthesia and congenital diaphragmatic hernia. Infants will also be excluded if their parents refuse to give consent to this study. During the study, if there are any signs of respiratory compromise, the study will be abandoned and ventilatory support given according to the Australian Neonatal Resuscitation guidelines.

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Convenience sample
Timing
Prospective
Statistical methods / analysis
This is the first study that attempts to characterize and define ECO2 values in spontaneously breathing infants from birth through the first day of life. We plan to recruit a convenience sample of 100 infants, 50 infants born via vaginal delivery and 50 infants born via caesarian section, during a 12 month period of study. According the RWH annual report, there were over 7,000 deliveries in 2013, over 5,000 of which would be eligible to approach for consent. We believe that 100 patients will allow us to obtain sufficient data to describe the patterns of exhaled CO2.

Infants will be recruited over a period of 12 months. Approximately another month will be required to collect hospital data on all infants enrolled. Medical data on each infant will be collected on Case Report Forms (Patient Data Form, RISE Study, included). De-identified information will be collected via the NM3 Respiratory Profile Monitor (Phillips Healthcare, Massachusetts, USA).

We aim to record the exact timing of several events that occur in the first minutes after the birth of the neonate, including the time the facemask is applied, the time the cord is clamped, the time the baby first breaths/cries, and the time that the pulse oximetry sensor is placed on the baby’s right wrist. We will account for these events by making a de-identified audio recording of the investigator dictating the sequence of events into an audio recorder (an iPhone placed in the investigator’s shirt pocket). Immediately after the delivery, we will record the timing of events onto a patient data form and erase the audio recording. All this information will then be entered into Stata database for analysis.

The primary outcome for this study will be the average ECO2 levels obtained every minute for the first ten minutes of life, than once at 1-2 hours of life and at 12-72 hours of life. ECO2 will be averaged over 10 breaths that correspond closest to each time point. Only values obtained with minimal facemask leak (less than 20% determined by analysis of inspiratory versus expiratory tidal volume) will be eligible for analysis. We will use a mean (SD) for continuous variables (birth weight, gestational age) and post hoc analysis of waveforms data to describe changes of expired CO2 after birth.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
25/02/2015
Actual
8/03/2016
Date of last participant enrolment
Anticipated
31/01/2017
Actual
8/03/2017
Date of last data collection
Anticipated
1/02/2017
Actual
22/03/2017
Sample size
Target
100
Accrual to date
Final
101
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 3430 0
The Royal Women's Hospital - Parkville
Recruitment postcode(s) [1] 9196 0
3052 - Parkville

Funding & Sponsors
Funding source category [1] 290721 0
Government body
Name [1] 290721 0
National Health and Medical Research Council Program Grant
Country [1] 290721 0
Australia
Funding source category [2] 290722 0
Hospital
Name [2] 290722 0
The Royal Women's Hospital
Country [2] 290722 0
Australia
Primary sponsor type
Individual
Name
Prof Peter Davis
Address
The Royal Women's Hospital
Cnr Grattan Street & Flemington Road
Locked Bag 300
Parkville, VIC 3052
Country
Australia
Secondary sponsor category [1] 289409 0
Individual
Name [1] 289409 0
Dr Omar Kamlin
Address [1] 289409 0
The Royal Women's Hospital
Cnr Grattan Street & Flemington Road
Locked Bag 300
Parkville, VIC 3052
Country [1] 289409 0
Australia
Other collaborator category [1] 278335 0
Individual
Name [1] 278335 0
Mr Kevyn Nyland
Address [1] 278335 0
The Royal Women's Hospital
Cnr Grattan Street & Flemington Road
Locked Bag 300
Parkville, VIC 3052
Country [1] 278335 0
Australia
Other collaborator category [2] 278336 0
Individual
Name [2] 278336 0
Dr Jennifer Dawson
Address [2] 278336 0
The Royal Women's Hospital
Cnr Grattan Street & Flemington Road
Locked Bag 300
Parkville, VIC 3052
Country [2] 278336 0
Australia
Other collaborator category [3] 278337 0
Individual
Name [3] 278337 0
Dr Stefan Kane
Address [3] 278337 0
The Royal Women's Hospital
Cnr Grattan Street & Flemington Road
Locked Bag 300
Parkville, VIC 3052
Country [3] 278337 0
Australia
Other collaborator category [4] 278338 0
Individual
Name [4] 278338 0
Dr Graeme Polglase
Address [4] 278338 0
The Ritchie Centre
MIMR-PHI Institute of Medical Research
27-31 Wright Street, Clayton, VIC 3168
Country [4] 278338 0
Australia
Other collaborator category [5] 278339 0
Individual
Name [5] 278339 0
Prof Stuart Hooper
Address [5] 278339 0
The Ritchie Centre
MIMR-PHI Institute of Medical Research
27-31 Wright Street, Clayton, VIC 3168
Country [5] 278339 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292359 0
The Royal Women's Hospital Research and Human Research Ethics Committees
Ethics committee address [1] 292359 0
Ethics committee country [1] 292359 0
Australia
Date submitted for ethics approval [1] 292359 0
28/10/2014
Approval date [1] 292359 0
03/02/2015
Ethics approval number [1] 292359 0
14/43

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 305 305 0 0
/AnzctrAttachments/367945-RISE_protocol v7 3 Feb 2015.doc
Attachments [2] 306 306 0 0
/AnzctrAttachments/367945-RISE study 14.43 Ethics approval.pdf

Contacts
Principal investigator
Name 54838 0
Dr Douglas Blank
Address 54838 0
The Royal Women's Hospital
Cnr Grattan Street & Flemington Road
Locked Bag 300
Parkville, VIC 3052
Country 54838 0
Australia
Phone 54838 0
+61422305487
Fax 54838 0
Email 54838 0
[email protected]
Contact person for public queries
Name 54839 0
Douglas Blank
Address 54839 0
The Royal Women's Hospital
Cnr Grattan Street & Flemington Road
Locked Bag 300
Parkville, VIC 3052
Country 54839 0
Australia
Phone 54839 0
+61422305487
Fax 54839 0
Email 54839 0
[email protected]
Contact person for scientific queries
Name 54840 0
Douglas Blank
Address 54840 0
The Royal Women's Hospital
Cnr Grattan Street & Flemington Road
Locked Bag 300
Parkville, VIC 3052
Country 54840 0
Australia
Phone 54840 0
+61422305487
Fax 54840 0
Email 54840 0
[email protected]

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