Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615001069549
Ethics application status
Approved
Date submitted
26/08/2015
Date registered
13/10/2015
Date last updated
13/11/2019
Date data sharing statement initially provided
13/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
High Flow Nasal Cannula Dose Finding Study in Neonatal Intensive Care
Scientific title
What is the effect of different delivered flow rates on the work of breathing in infants requiring respiratory support?
Secondary ID [1] 287349 0
Nil known
Universal Trial Number (UTN)
U1111-1173-6647
Trial acronym
HiFiDo
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Respiratory distress 296013 0
premature birth 296349 0
bronchiolitis 296350 0
Condition category
Condition code
Respiratory 296292 296292 0 0
Other respiratory disorders / diseases
Reproductive Health and Childbirth 296625 296625 0 0
Complications of newborn

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
High flow nasal cannula will be delivered to infants with flow rates randomly applied. For preterm infants the flow rates will be between 2L/min and 8L/min in 2L steps. For infants with bronchiolitis, flow rates between 0.5 L/kg/min and 2 L/kg/min will be randomly applied in 0.5 L/Kg/min steps. After each flow rate change an equilibration phase of 10 minutes will be allowed before undertaking a 5 minute measurement. Each of the 4 flow rates will be applied for 15 minutes. The total study duration will be 2 hours.
Intervention code [1] 292689 0
Treatment: Devices
Intervention code [2] 292969 0
Treatment: Other
Comparator / control treatment
Participants act as their own controls
Control group
Active

Outcomes
Primary outcome [1] 295945 0
Work of breathing will be measured with diaphragmatic electrical activity (Edi) and respiratory inductance plethysmography (RIP) as a standard measurement technique.
Timepoint [1] 295945 0
10 minutes after each flow rate change
Secondary outcome [1] 316994 0
Physiological outcomes - Respiratory rate (RR) assessed using bedside monitor
Timepoint [1] 316994 0
10 minutes after each flow rate change
Secondary outcome [2] 317928 0
SpO2/FiO2 - calculated using the values for oxygen saturation assessed from the bedside monitor and inspired oxygen as delivered by the oxygen blender
Timepoint [2] 317928 0
10 minutes after each flow rate change
Secondary outcome [3] 317929 0
Heart rate (HR) assessed using bedside monitor
Timepoint [3] 317929 0
10 minutes after each flow rate change.
Secondary outcome [4] 317930 0
Oxygen saturation (SpO2) assessed using bedside monitor
Timepoint [4] 317930 0
10 minutes after each flow rate change.

Eligibility
Key inclusion criteria
Preterm group
Infants at 28 – 36 weeks corrected gestational age
Are currently treated with nCPAP
Are currently deemed stable enough by the treating medical and nursing staff to go onto HFNC
Have an FiO2 requirement less than or equal to 0.40
Nasogastric (ng) feeding tube in place
Parent(s) or guardian able and willing to provide informed consent

Bronchiolitis group
Clinical diagnosis of bronchiolitis with increased WOB (retraction, auxiliary respiratory muscle use) and respiratory distress due to viral infection
An oxygen requirement treated with high flow in ICU
Aged 0-12 months
Nasogastric (ng) feeding tube in place
Parent(s) or guardian able and willing to provide informed consent
Minimum age
No limit
Maximum age
12 Months
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Lung or cardiovascular anomaly that would substantially affect oxygenation, lung recruitment or regional ventilation, e.g.;
Cyanotic or other major congenital heart disease (not including Patent Ductus Arteriosus)
Craniofacial malformations or congenital disease affecting the respiratory system
More than 2 episodes within the last hour of apnoea and/or bradycardia requiring moderate or vigorous stimulation and an increase in FiO2 or change in CPAP pressure

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)
Flow rates will be randomly applied.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be undertaken by study personnel using a computer generated randomisation with allocation concealment by sequentially numbered sealed opaque envelopes
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Data will be described using means and 95% confidence intervals. Standard deviation scores (SDS) will be used to describe changes from baseline, with a twofold sustained increase in SDS considered significant. ANOVA with Bonferoni correction for repeated measurements will also be used. A p-value of <0.05 will be considered statistically significant. A convenience sample of 16 premature infants will be used and 30 infants with bronchiolitis. Based on our previous studies, we can expect that 2 L/kg/min air flow causes an increase of continuous distending pressure by 4.5 cmH2O (SD 2.7, n = 13). We expect a similar effect in the current study on Edi. Using a power of 90% and a P-value of < 0.05 we need to enrol approximately 12-15 patients

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
2/11/2015
Actual
29/05/2016
Date of last participant enrolment
Anticipated
31/12/2019
Actual
Date of last data collection
Anticipated
31/12/2019
Actual
Sample size
Target
46
Accrual to date
29
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 4266 0
Mater Mother's Hospital - South Brisbane
Recruitment hospital [2] 15145 0
Queensland Children's Hospital - South Brisbane
Recruitment postcode(s) [1] 10211 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 291910 0
Charities/Societies/Foundations
Name [1] 291910 0
Betty McGrath Research Fellowship, Mater Health Services and Mater Research
Country [1] 291910 0
Australia
Funding source category [2] 294697 0
University
Name [2] 294697 0
Australian Catholic University
Country [2] 294697 0
Australia
Primary sponsor type
Hospital
Name
Mater Health Services
Address
Mater Health Services,
Raymond Terrace
South Brisbane, QLD 4101
Country
Australia
Secondary sponsor category [1] 290579 0
Hospital
Name [1] 290579 0
Queensland Children's Hospital
Address [1] 290579 0
501 Stanley St
South Brisbane
Qld 4101
Country [1] 290579 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293417 0
Mater Health Services
Ethics committee address [1] 293417 0
Raymond Terrace
South Brisbane, Qld 4101
Ethics committee country [1] 293417 0
Australia
Date submitted for ethics approval [1] 293417 0
28/07/2015
Approval date [1] 293417 0
15/09/2015
Ethics approval number [1] 293417 0
HREC/15/MHS/68

Summary
Brief summary
Delivery of air flow by high flow nasal cannula (HFNC) has become increasingly popular in neonatal and paediatric intensive care units throughout Australia and the world. Despite this, there is limited knowledge on how to determine the most appropriate flow rate for the infant. This study will measure the electrical activity of the diaphragm to determine when the work of breathing is optimal and then examine what other physiological measures correlate with this. The aim of this study is to demonstrate the physiological effect of randomly applied levels of high flow on the work of breathing (WOB) indirectly measured with electric diaphragmatic activity.
Methods: This is a prospective interventional study of premature infants with respiratory distress admitted to the Neonatal Critical Care Unit (NCCU), Mater Mothers Hospital, South Brisbane and infants with bronchiolitis admitted to Lady Cilento Childrens Hospital (LCCH).
Work of breathing (WOB) will be measured with diaphragmatic electrical activity - measured transoesophageal (Edi)and transdermal (Tdi), and respiratory inductance plethysmography (RIP). Using the Edi signals we will measure the WOB during HFNC treatment and assess its impact on patients with respiratory distress. Edi requires inserting a specially designed sensing nasogastric tube into the infants’ nose, Tdi involves placing five regular skin elecrodes on the chest, and RIP consists of two stretch bands placed around the chest and abdomen. Both Edi and RIP signal can be recorded continuously during the entire study period and recorded on a dedicated computer and further analysed.
Physiological variables of respiratory rate (RR), heart rate (HR), and oxygen saturations (SpO2) will also be monitored throughout the study. From the collected data the SpO2/FiO2 ratio will be calculated.
Study Procedure: Infants recruited into the trial will be on HFNC oxygen therapy using the Fisher & Paykel 850 humidifier. The in situ nasogastric tube will be replaced by the Edi probe. The first measurement will be done when the infant is settled but within the first 24 hours of HFNC administration. Thereafter, flow rates between 2 and 8 L /min will be randomly applied for the preterm infant and between 0.5 L/kg/min and 2 L/kg/min for the infants with bronchiolitis. At the conclusion, initial HFNC settings will be reinstituted.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 545 545 0 0
/AnzctrAttachments/369196-HF_dose finding_Research Proposal_V2_150728.docx

Contacts
Principal investigator
Name 59842 0
Dr Judy Hough
Address 59842 0
Physiotherapy Department
Mater Health Services
Raymond Terrace
South Brisbane
Qld 4101
Country 59842 0
Australia
Phone 59842 0
+61 422404369
Fax 59842 0
Email 59842 0
judith.hough@mater.org.au
Contact person for public queries
Name 59843 0
Dr Judy Hough
Address 59843 0
Physiotherapy Department
Mater Health Services
Raymond Terrace
South Brisbane
Qld 4101
Country 59843 0
Australia
Phone 59843 0
+61 422404369
Fax 59843 0
Email 59843 0
judith.hough@mater.org.au
Contact person for scientific queries
Name 59844 0
Dr Judy Hough
Address 59844 0
Physiotherapy Department
Mater Health Services
Raymond Terrace
South Brisbane
Qld 4101
Country 59844 0
Australia
Phone 59844 0
+61 422404369
Fax 59844 0
Email 59844 0
judith.hough@mater.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Confidentiality


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
5648Study protocol  judith.hough@mater.org.au
5649Statistical analysis plan  judith.hough@mater.org.au
5650Informed consent form  judith.hough@mater.org.au
5651Ethical approval  judith.hough@mater.org.au



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

Documents added automatically
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