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Trial registered on ANZCTR


Registration number
ACTRN12619000740190
Ethics application status
Approved
Date submitted
22/03/2019
Date registered
17/05/2019
Date last updated
17/05/2019
Date data sharing statement initially provided
17/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Studies of apnoea in the newborn: Delivery of positive inflating pressure as early rescue
Scientific title
The SANDPIPER study: Delivery of positive inflation pressure as early rescue triggered by respiratory pause in preterm infants <30 weeks gestation on bubble CPAP
Secondary ID [1] 297613 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
SANDPIPER study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Apnoea of prematurity 311882 0
Condition category
Condition code
Respiratory 310471 310471 0 0
Other respiratory disorders / diseases
Reproductive Health and Childbirth 310777 310777 0 0
Complications of newborn

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This will be a 16 hour crossover study consisting of 4 periods, each of 4 hours duration. Both the first and second halves of the study will consist of a control and intervention epoch at random. During each intervention epoch, positive inflating pressure (PIP) triggered by 3 seconds of apnoea will be delivered either singly (sPIP) or repetitively (rPIP, up to 3 inflations). The maximum pressure of 18 cmH2O will be delivered via a PIP generating device, coupled to the existing CPAP circuit. A minimum washout period of 15 minutes will occur between each epochs.

To monitor fidelity, UTAS researchers will be on-site during intervention period. Additionally, CPAP pressures are measured and recorded throughout the 16 hour study period. Bedside staff are not required to monitor or manage the PIP generator beyond their usual interaction with the normal CPAP circuit.
Intervention code [1] 313852 0
Treatment: Devices
Comparator / control treatment
Two 4 hour epochs of standard care - CPAP only, without rescue positive inflation pressure (PIP). CPAP setting would be determined by bedside staff based on clinical needs, and will vary from patient to patient, ranging from 5 to 10cmH2O.
Control group
Active

Outcomes
Primary outcome [1] 319341 0
Change in frequency of apnoea lasting >5 seconds, expressed as events per hour , and quantified both on a per study and per infant basis will be compared between each epoch.

Events of apnoea will be determined and recorded via the Dräger Infinity monitor - a standard clinical monitoring device - and a modified Graseby MR10 respiratory monitor.
Timepoint [1] 319341 0
End of the study period for each infant - approximately 16 hours.
Secondary outcome [1] 367833 0
Change in frequency of apnoea lasting >10 seconds, expressed as events per hour , and quantified both on a per study and per infant basis will be compared between each epoch.

Events of apnoea will be determined and recorded via the Dräger Infinity monitor - a standard clinical monitoring device - and a modified Graseby MR10 respiratory monitor.

This outcome will be used to assess the effectiveness of the intervention.
Timepoint [1] 367833 0
End of the study period for each infant - approximately 16 hours.
Secondary outcome [2] 368922 0
Change in frequency of apnoea as per a consensus definition (>20 seconds or >10 seconds if accompanied by hypoxia and/or bradycardia), expressed as events per hour , and quantified both on a per study and per infant basis will be compared between each epoch.

Events of apnoea will be determined and recorded via the Dräger Infinity monitor - a standard clinical monitoring device - and a modified Graseby MR10 respiratory monitor.

This outcome will be used to assess the effectiveness of the intervention.
Timepoint [2] 368922 0
End of the study period for each infant - approximately 16 hours.
Secondary outcome [3] 368923 0
Total duration of apnoea lasting >5 seconds will be compared between each epoch.

Events of apnoea will be determined and recorded via the Dräger Infinity monitor - a standard clinical monitoring device- and a modified Graseby MR10 respiratory monitor.

This outcome will be used to assess the effectiveness of the intervention.
Timepoint [3] 368923 0
End of the study period for each infant - approximately 16 hours.
Secondary outcome [4] 368924 0
Change in frequency of hypoxia (SpO2 <85%) within 60 seconds of apnoea onset, expressed as events per hour, and quantified both on a per study and per infant basis will be compared between each epoch.

Events of apnoea will be determined and recorded via the Dräger Infinity monitor - a standard clinical monitoring device- and a modified Graseby MR10 respiratory monitor.

These outcomes will be used to assess the effectiveness of the intervention.
Timepoint [4] 368924 0
End of the study period for each infant - approximately 16 hours.
Secondary outcome [5] 368925 0
Change in frequency of bradycardia (HR<100bpm) within 60 seconds of apnoea onset, expressed as events per hour, and quantified both on a per study and per infant basis will be compared between each epoch.

Events of apnoea will be determined and recorded via the Dräger Infinity monitor - a standard clinical monitoring device.

This outcome will be used to assess the effectiveness of the intervention.
Timepoint [5] 368925 0
End of the study period for each infant - approximately 16 hours.
Secondary outcome [6] 368926 0
Proportion of time during which the abdominal capsule recording was missing and/or uninterpretable.

Recordings will be made using a modified Graseby MR10 respiratory monitor.

This outcome will be used to assess the functionality of the PIP generator device.
Timepoint [6] 368926 0
End of the study period for each infant - approximately 16 hours.
Secondary outcome [7] 368927 0
Average delivered peak inflating pressure over each intervention periods.

Delivered pressure will be measured and recorded with a Fisher and Paykel Proxytrack.

This outcome will be used to assess the functionality of the PIP generator device.
Timepoint [7] 368927 0
End of the study period for each infant - approximately 16 hours.
Secondary outcome [8] 368928 0
Frequency of instances where measured inflating pressure is <3 cm H2O above background CPAP level.

Delivered pressure will be measured and recorded with a Fisher and Paykel Proxytrack.

This outcome will be used to assess the functionality of the PIP generator device.
Timepoint [8] 368928 0
End of the study period for each infant - approximately 16 hours.
Secondary outcome [9] 368929 0
Frequency of instances where there are no change in respiratory signal following PIP generation.

Respiration waveform and pulse will be recorded via the Dräger Infinity monitor - a standard clinical monitoring device- and a modified Graseby MR10 respiratory monitor. Delivered pressure will be measured and recorded with a Fisher and Paykel Proxytrack.

This outcome will be used to assess the functionality of the PIP generator device.
Timepoint [9] 368929 0
End of the study period for each infant - approximately 16 hours.
Secondary outcome [10] 368930 0
Incidence of actuation of positive inflating pressure during the expiratory phase.

Respiratory waveforms will be recorded via the Dräger Infinity monitor - a standard clinical monitoring device. Delivered pressure will be measured and recorded with a Fisher and Paykel Proxytrack.

This outcome will be used to assess the safety of the PIP generator.
Timepoint [10] 368930 0
End of the study period for each infant - approximately 16 hours.
Secondary outcome [11] 368931 0
Requirement to de-activate PIP generator or cease intervention by UTAS researcher or bedside staff.

This outcome will measured from the electronic logs of PIP generator function, and will be used to assess the safety of the PIP generator.
Timepoint [11] 368931 0
End of the study period for each infant - approximately 16 hours.
Secondary outcome [12] 370504 0
Change in frequency of apnoea lasting >15 seconds, expressed as events per hour, and quantified both on a per study and per infant basis will be compared between each epoch.

Events of apnoea will be determined and recorded via the Dräger Infinity monitor - a standard clinical monitoring device - and a modified Graseby MR10 respiratory monitor.

This outcome will be used to assess the effectiveness of the intervention.
Timepoint [12] 370504 0
End of the study period for each infant - approximately 16 hours.
Secondary outcome [13] 370505 0
Change in frequency of hypoxia (SpO2 <80%) within 60 seconds of apnoea onset, expressed as events per hour, and quantified both on a per study and per infant basis will be compared between each epoch.

Events of apnoea will be determined and recorded via the Dräger Infinity monitor - a standard clinical monitoring device- and a modified Graseby MR10 respiratory monitor.

These outcomes will be used to assess the effectiveness of the intervention.
Timepoint [13] 370505 0
End of the study period for each infant - approximately 16 hours.

Eligibility
Key inclusion criteria
- Birth gestation <30 weeks
- Chronological age < /=4 months
- Supported with bubble CPAP
- Having frequent respiratory pauses 5+ seconds duration, resulting in episodes of hypoxia (SpO2 <85) and/or bradycardia (heart rate <100 bpm) at least twice per hour.
- Research team available to commence study
- Agreement of treating clinician that the infant is suitable for involvement in the study
- Signed parental consent
Minimum age
No limit
Maximum age
4 Months
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Change in mode of respiratory support, including use of non-triggered continuous non-invasive positive pressure ventilation (NIPPV) being contemplated in next 24 hours

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)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The sequence of interventions will be determined using randomisation schedule provided by the collaborating statistician at Menzies Institute for Medical Research, University of Tasmania.

The randomisation will be constrained such that the first and second 8 hour blocks of the 16 hour study each contains a period of CPAP.

Access to the randomisation will be restricted, and the intervention sequence will only be revealed once preparation of the bedspace and the infant has been completed. The randomisation for the second of two 16 hour crossover studies will only be revealed once the first study is completed.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Sample size calculations for the SANDPIPER study are based in part on the data generated in preterm infants in the SANTO-B study, where there were 9.3±11 respiratory pause events per hour in preterm infants on CPAP, as noted above. Given the crossover nature of the study design, the crux of the analysis will be a comparison of the difference in event numbers between the intervention periods and the standard CPAP periods. Assuming that the difference in event frequency between intervention and control groups has a standard deviation of 5 per hour, and applying standard paired statistical methodology, then detection of a difference in event frequency of 3 per hour with 80% power and a=0.05 would require the conduct of 22 studies. Given that this calculation does not take into account the lack of independence of studies performed in the same infant, we will plan to perform 40 studies in at least 20 infants. This will also allow collection of sufficient data (~640 hrs of recordings) to perform our analyses.

Note that our projection of a 3 per hour decrease in the rate of respiratory pauses would represent a meaningful clinical improvement in the frequency of this potentially destabilising complication in preterm infants on CPAP.

Recruitment
Recruitment status
Not yet 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)
TAS
Recruitment hospital [1] 13310 0
Royal Hobart Hospital - Hobart
Recruitment postcode(s) [1] 25883 0
7000 - Hobart

Funding & Sponsors
Funding source category [1] 302158 0
Hospital
Name [1] 302158 0
Royal Hobart Hospital
Address [1] 302158 0
Royal Hobart Hospital, 48 Liverpool St, Hobart, Tasmania 7000
Country [1] 302158 0
Australia
Primary sponsor type
University
Name
University of Tasmania
Address
University of Tasmania
Private Bag 51
HOBART TAS 7001
Country
Australia
Secondary sponsor category [1] 302187 0
None
Name [1] 302187 0
Address [1] 302187 0
Country [1] 302187 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302837 0
Tasmanian Health and Medical Human Research Ethics Committee (HREC)
Ethics committee address [1] 302837 0
Menzies Institute for Medical Research, 17 Liverpool St, Hobart, Tasmania 7000
Ethics committee country [1] 302837 0
Australia
Date submitted for ethics approval [1] 302837 0
18/02/2019
Approval date [1] 302837 0
10/05/2019
Ethics approval number [1] 302837 0
H0017948

Summary
Brief summary
We will investigate whether delivery of positive inflation pressure (PIP) (singly or repeated), triggered by a 3 second pause in respiration, can re-establish breathing efforts in preterm infants on continuous positive airway pressure (CPAP), a form of non-invasive respiratory support.

The study will involve infants born at <30 weeks gestation who require CPAP support, and are having episodes of respiratory pauses. We will conduct a 16 hours crossover study comparing the use of a device to generate PIP with standard CPAP support. The study will be in blocks of 4 hours (randomly assigned) in which PIP is delivered singly, repeatedly (up to 3), or not at all (standard CPAP).

We hypothesise that PIP will improve the regularity of breathing, and shorten the duration of respiratory pauses.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 91562 0
Prof Peter Dargaville
Address 91562 0
Department of Paediatrics, Royal Hobart Hospital, 48 Liverpool St, Hobart, TAS 7000
Country 91562 0
Australia
Phone 91562 0
+61361667546
Fax 91562 0
Email 91562 0
peter.dargaville@ths.tas.gov.au
Contact person for public queries
Name 91563 0
Prof Peter Dargaville
Address 91563 0
Department of Paediatrics, Royal Hobart Hospital, 48 Liverpool St, Hobart, TAS 7000
Country 91563 0
Australia
Phone 91563 0
+61361667546
Fax 91563 0
Email 91563 0
peter.dargaville@ths.tas.gov.au
Contact person for scientific queries
Name 91564 0
Prof Peter Dargaville
Address 91564 0
Department of Paediatrics, Royal Hobart Hospital, 48 Liverpool St, Hobart, TAS 7000
Country 91564 0
Australia
Phone 91564 0
+61361667546
Fax 91564 0
Email 91564 0
peter.dargaville@ths.tas.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results