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Trial registered on ANZCTR


Registration number
ACTRN12613000124730
Ethics application status
Approved
Date submitted
9/01/2013
Date registered
1/02/2013
Date last updated
1/02/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
Control of breathing and measurement of disease severity in premature infants with chronic lung disease
Scientific title
In preterm infants with bronchopulmonary dysplasia (BPD) would alterations in inspired oxygen concentrations induce changes that would allow chemoreceptor reflex activity and VQ mismatch to be measured
Secondary ID [1] 281712 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bronchopulmonary dysplasia 288012 0
Prematurity 288019 0
Condition category
Condition code
Respiratory 288387 288387 0 0
Other respiratory disorders / diseases
Reproductive Health and Childbirth 288395 288395 0 0
Complications of newborn

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Change in concentration of inspired oxygen (FiO2). The steps are detail as follows. Stepwise reduction/increase steps in the FiO2 (of 1-2%) separated by 5 minutes will be made while maintaining the oxygen saturation within the unit's oximeter alarm limits of 88-96% for infants >36 weeks PMA. Once the lower/upper alarm limit is reached, we propose to reverse the stepwise change until the upper/lower limit is reached; so that we can determine the FiO2 limits (range setting phase) whereby the infant can maintain SpO2 within the reference range in his/her current state.
Then we proposed to make a discrete change in the FiO2 to the other end of the range and maintain for between 15-30 seconds and then revert to the opposite extreme. After this, the FiO2 will be returned to its original level. The order in which the FiO2 is either increased or decreased will be randomised.
Intervention code [1] 286252 0
Treatment: Other
Comparator / control treatment
Infants without BPD or infants without need for oxygen or respiratory support
Control group
Active

Outcomes
Primary outcome [1] 288558 0
Patterns of breathing in response to change in oxygen concentration. This will be measured in terms of two parameters, i.e. capnography and chest/abdominal wall excursion.

In brief, capnography will be measured via Respironics NM3 sensor (Philips Healthcare, North Ryde NSW). This will be a side-stream continuous flow measurement whereby exhaled end-tidal CO2 will be measured by a capnometer.

Chest and abdominal wall excursion will be measured via chest impedance (CI) or respiratory inductance plethysmography (RIP). We intend to measure chest and abdominal wall excursion utilising either chest impedance (CI) via ECG gel electrodes placed on the chest using the Agilent monitors AgilentTM (Agilent Technologies, Forest Hill VIC). If chest wall impedance is not available, we will utilise the “Respi-Band” respiratory inductance plethysmography (Sensormedics, Yorba Linda CA). Specifically, we also intend to measure for thoraco-abdominal wall asynchrony, i.e phase-angle and phase relation.
Timepoint [1] 288558 0
End of intervention (i.e. change in the concentration of inspired oxygen)
Primary outcome [2] 288566 0
Levels of intrapulmonary shunting or ventilation-perfusion (VQ) mismatch. This will be a derived variable obtained from plotting concentration of inspired oxygen obtained from the mechanical ventilators (Babylog 8000plus or SLE5000) against oxygen saturation obtained from pulse oximeters Masimo Radical 7 (Masimo Australia Pty Ltd, French Forest NSW) on an FiO2/SpO2 graph.
Timepoint [2] 288566 0
End of the intervention (i.e. change in the concentration of inspired oxygen)
Secondary outcome [1] 300464 0
Changes in oxygen saturation (SpO2). This will be obtained from pulse oximeters, namely the Masimo Radical 7 (Masimo Australia Pty Ltd, French Forest NSW) pulse oximeter will be recorded concurrently into the Powerlab system. SpO2 averaging time will be set as per current Monash Newborn NICU usage at 8 seconds. During the study, oximetry will be recorded from the right upper limb (i.e. pre-ductal oxygen saturation). A second Masimo pulse oximeter will also record at 2 seconds averaging time (with the display concealed) from research and nursing staff.
Timepoint [1] 300464 0
End of intervention (i.e. change in the concentration of inspired oxygen)
Secondary outcome [2] 300476 0
Periodic breathing cycle duration. This will be derived from calculations obtained from the Powelab physiological monitoring system.
Timepoint [2] 300476 0
End of the study period (i.e. change in the concentration of inspired oxygen)
Secondary outcome [3] 300538 0
Measurements of the stability of the infants' respiratory control mechanism quantified by measurements called loop gain (LG) which will be derived via analysis of the data. The methods are set out in a paper by Edwards et al 2009, although in this case SpO2 will be used rather than pO2.

Edwards BA, Sands SA, Feeney C, et al. Continuous positive airway pressure reduces loop gain and resolves periodic central apneas in the lambRespiratory Physiology & Neurobiology 168 (2009) 239–249
Timepoint [3] 300538 0
End of the intervention (i.e. change in the concentration of inspired oxygen)

Eligibility
Key inclusion criteria
Preterm infants < 29 weeks gestation.
1. Healthy preterm infant (<29 weeks) without BPD

Infants with BPD defined as need for oxygen or respiratory support at 36 weeks completed postmenstrual age (PMA).

Infants will be further subdivided into
2. Mild BPD (no need for oxygen or respiratory support at 36 weeks PMA but need for either at 28 days of age).

3. Moderate BPD - need for supplemental oxygen (<30%) at 36 weeks PMA butself-ventilating

4. Severe BPD - need for supplemental oxygen (>30%) at 36 weeks PMA or needing respiratory support.

Infants in Group 1, the healthy preterm infant will be the control group while infants in Groups 2 to 4 with mild/moderate/severe BPD will be in the intervention group
Minimum age
36 Weeks
Maximum age
44 Weeks
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Infants with congenital heart disease
Infants with major congenital anomalies

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)
Patient will be identified from the admissions list.
Randomisation will be performed and concealed by opaque sealed envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety
Statistical methods / analysis

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] 346 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment postcode(s) [1] 6142 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 286529 0
University
Name [1] 286529 0
The Ritchie Centre
Monash Institute of Medical Research
Monash University
Address [1] 286529 0
The Ritchie Centre
Monash Institute of Medical Research
246 Clayton Road
Clayton
VIC 3168
Country [1] 286529 0
Australia
Funding source category [2] 286530 0
Charities/Societies/Foundations
Name [2] 286530 0
Financial Markets Foundation for Children
Address [2] 286530 0
Foundation for Children
GPO Box 3655
Sydney
NSW 2000

Country [2] 286530 0
Australia
Primary sponsor type
University
Name
The Ritchie Centre, Monash University
Address
The Ritchie Centre
Monash Institute of Medical Research
246 Clayton Road
Clayton
VIC 3168
Country
Australia
Secondary sponsor category [1] 285318 0
Hospital
Name [1] 285318 0
Monash Newborn
Monash Children's
Address [1] 285318 0
Monash Medical Centre
246 Clayton Road
Clayton
Victoria 3168
Country [1] 285318 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288579 0
Southern Health Human Research Ethics Committee B
Ethics committee address [1] 288579 0
Monash Medical Centre
246 Clayton Road
Clayton
Victoria 3168
Ethics committee country [1] 288579 0
Australia
Date submitted for ethics approval [1] 288579 0
Approval date [1] 288579 0
05/12/2012
Ethics approval number [1] 288579 0
12284B

Summary
Brief summary
Apnoea of prematurity (AOP), where an infant stops breathing for more than 20seconds, is found in over half of babies born very prematurely. AOP may be accompanied by slowing of the heart rate as well as drop in the blood oxygen levels. Another form of breathing disorder called periodic breathing, is found primarily in premature infants where there is a repetitive pattern of breathing efforts alternating with pauses. Most preterm infants exhibit periodic breathing and it can continue until the infant reaches 4-6 months of age.

Apart from breathing control disorderm preterm babies are also at risk of developing bronchopulmonary dysplasia (BPD) or chronic lung disease of prematurity, where there the injured premature lung develops in an abnormal way. There is still some debate about the best way of classifying this disease with the NICHD in the United States dividing this into three levels (mild, moderate and severe) based on the need for oxygen or respiratory
support.

Infants with BPD experience periods of low blood oxygen that may be severe, especially during sleep and these infants are thought to be at risk of sudden infant death syndrome (SIDS) or cot death. The major cause of oxygenation problems in BPD is due to the severity of the lung disease. The level of the lung disease will determine how much oxygen gets absorbed into the blood of the baby with every breath. A reliable way of determing the severity is by measuring how much the blood gets "oxygenated", i.e. the less severe the lung disease the better the oxygenation and vice versa. This measure is also called the right-to-left shunting and the ventilation: perfusion (V:Q )ratio. A nonivasive way of measuring the shunt will involve making stepwise reductions in oxygen that the baby breathes while ensuring that the oxygen level (that is constantly monitored) remains within intended range.

The aim of this study is to investigate 1) firstly breathing patterns (or disorders) and develop tools for classifying breathing patterns and 2) secondly lung disease severity (right-left shunts) and develop quantitative measures of these in preterm infants with bronchopulmonary dysplasia or chronic lung disease.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 36774 0
Dr Kenneth Tan
Address 36774 0
Monash Newborn
Monash Medical Centre
246 Clayton Road
Clayton
Victoria 3168
Country 36774 0
Australia
Phone 36774 0
+61395945191
Fax 36774 0
Email 36774 0
kenneth.tan@monash.edu
Contact person for public queries
Name 36775 0
Dr Kenneth Tan
Address 36775 0
Monash Newborn
Monash Medical Centre
246 Clayton Road
Clayton
Victoria 3168
Country 36775 0
Australia
Phone 36775 0
+61395945191
Fax 36775 0
Email 36775 0
kenneth.tan@monash.edu
Contact person for scientific queries
Name 36776 0
Dr Kenneth Tan
Address 36776 0
Monash Newborn
Monash Medical Centre
246 Clayton Road
Clayton
Victoria 3168
Country 36776 0
Australia
Phone 36776 0
+61395945191
Fax 36776 0
Email 36776 0
kenneth.tan@monash.edu

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