Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000283572
Ethics application status
Approved
Date submitted
1/02/2024
Date registered
20/03/2024
Date last updated
21/07/2024
Date data sharing statement initially provided
20/03/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparing the effects of high flow nasal oxygen versus face mask oxygen on expired end tidal oxygen concentration after simulated preoxygenation of obese pregnant people
Scientific title
High flow humidified nasal oxygen versus face mask oxygen for preoxygenation of pregnant people with high body mass index – a prospective randomised controlled crossover non-inferiority study (HINOP3)
Secondary ID [1] 311435 0
None
Universal Trial Number (UTN)
U1111-1299-6843
Trial acronym
HINOP3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Preoxygenation 332721 0
Anaesthesia 332722 0
Obesity 332723 0
Pregnancy 332724 0
Condition category
Condition code
Anaesthesiology 329439 329439 0 0
Anaesthetics
Reproductive Health and Childbirth 329440 329440 0 0
Childbirth and postnatal care
Respiratory 329441 329441 0 0
Normal development and function of the respiratory system
Diet and Nutrition 329442 329442 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention will be preoxygenation with high flow humidified nasal oxygen for a total duration of 3 minutes according to the protocol as follows. The approximate total duration of the testing will take 30 minutes.

High flow humidified nasal oxygen protocol
With 10 l.min-1 of room air (FiO2 21%) running in the anaesthetic circuit, a tightly fitting face mask will be applied by a trained investigator (anaesthetist, anaesthetic registrar, medical student, or nurse) and a good seal and ideal fitting will be determined by observing the capnography trace as the woman breathes. (This step may be omitted if the participant undergoes the face mask oxygen protocol first as per randomization).

The face mask will then be removed. The oxygen concentration in the anaesthetic circuit will be increased to 100% (FiO2 100%) with flows remaining at 10 l.min-1 until the oxygen concentration rises to 100% as determined by real time oxygen analysis on the anaesthetic machine. After this has been achieved, high flow humidified nasal cannulae (Optiflow Switch™ by Fisher & Paykel Healthcare - TGA approved) will be placed into the woman’s nostrils by the trained investigator (anaesthetist, anaesthetic registrar, medical student, or nurse). The oxygen flow will be commenced (first 30 seconds at 30 l.min-1, then next 150 seconds at 70 l.min-1). Each woman will be instructed to breathe normally with her mouth closed as much as possible. The percentage of time mouth closure is achieved will be recorded to the closest percentage of 0%, 25%, 50%, 75% or 100%. If the maximum (70 l.min-1) flow rate is not tolerated, it will be reduced to 60 l.min-1 and then to 50 l.min-1 before aborting the protocol. At the end of three minutes the participant will be asked to hold their breath in inspiration while the tightly fitting face mask (connected to 10 l.min-1 FiO2 100%) will be applied over the nasal cannulae occluding the compressible arm. The woman will then be asked to exhale normally and breathe normally and the first four etO2 concentration values measured by the end tidal gas analyzer on the anaesthetic machine will be recorded. Other variables including end-tidal carbon dioxide concentration, peak oxygen saturation values and tidal volumes will be recorded.
Intervention code [1] 327878 0
Prevention
Intervention code [2] 328077 0
Treatment: Devices
Comparator / control treatment
Comparator treatment in this instance is face mask oxygen as it represents usual care in our institution's clinical setting. The protocol for "usual care" is defined below.

Randomised controlled crossover trial. Participants form their own controls as they undergo both simulated preoxygenation protocols in randomised order determined by their group.

Face mask oxygenation protocol
With 10 l.min-1 of room air (fraction of inspired oxygen (FiO2)21%) running in the anaesthetic circuit, a tightly fitting face mask will be applied by a trained investigator (anaesthetist, anaesthetic registrar, medical student, or nurse) and a good seal and ideal fitting will be determined by observing the capnography trace as the woman breathes and aiming for an “ideal” capnograph trace defined as a clear rectangular shaped waveform with identifiable baseline, rise, plateau and fall phases. The face mask will then be removed. The oxygen concentration in the anaesthetic circuit will be increased to 100% (FiO2 100%) with flows remaining at 10 l.min-1 until the oxygen concentration rises to 100% as measured by real time oxygen analysis on the anaesthetic machine. After this has been achieved, the tightly fitting face mask will be applied by a trained investigator for three minutes observing the capnography trace to ensure a good seal is maintained throughout this time. Each participant will be instructed to breathe normally. After three minutes elapse, the first four etO2 concentration values measured by the end tidal gas analyzer will be recorded.
Control group
Active

Outcomes
Primary outcome [1] 337259 0
Expired end tidal oxygen concentration
Timepoint [1] 337259 0
The first end tidal oxygen concentration value from the first expired breath after respective protocols completed at the timepoint just before the capnography trace changes from plateau to downward spike with a square end tidal waveform
Secondary outcome [1] 431242 0
Proportion of participants who achieved 90% or more end tidal oxygen respectively after HFNO and face mask oxygen
Timepoint [1] 431242 0
At time of statistical analysis (within one month after recruitment completion)
Secondary outcome [2] 431243 0
Proportion of participants who achieved 80% or more end tidal oxygen respectively after HFNO and face mask oxygen
Timepoint [2] 431243 0
At time of statistical analysis (within one month after recruitment completion)
Secondary outcome [3] 431248 0
Comfort scores
Timepoint [3] 431248 0
At the end trial experiment
Secondary outcome [4] 431249 0
Fetal heart rate
Timepoint [4] 431249 0
Before & after each modality protocol
Secondary outcome [5] 431250 0
End-tidal carbon dioxide concentration (maternal)
Timepoint [5] 431250 0
The first end tidal carbon dioxide concentration value from the first expired breath after respective protocols completed at the timepoint just before the capnography trace changes from plateau to downward spike with a square end tidal waveform
Secondary outcome [6] 431251 0
Oxygen saturation values (maternal)
Timepoint [6] 431251 0
Continuously - before, during & after protocols (i.e. high flow nasal oxygen protocol and face mask oxygen protocol). Measurement from one minute before first protocol until one minute after last protocol.
Secondary outcome [7] 431252 0
Respiratory rate (maternal)
Timepoint [7] 431252 0
Before & during protocols
Secondary outcome [8] 431253 0
Heart rate (maternal)
Timepoint [8] 431253 0
Continuously - before, during & after protocols. Measurement from one minute before first protocol until one minute after last protocol.
Secondary outcome [9] 431254 0
Blood pressure (maternal)
Timepoint [9] 431254 0
Every 3 minutes - before, during & after protocols. Measurement from one minute before first protocol until one minute after last protocol.
Secondary outcome [10] 431255 0
Tidal volume (maternal)
Timepoint [10] 431255 0
Measured every breath during face mask oxygen protocol only. Tidal volume measurement during high flow nasal oxygen protocol impossible due to nature of apparatus.
Secondary outcome [11] 431256 0
Minute ventilation (maternal)
Timepoint [11] 431256 0
Calculated during data analysis phase. Taken as minute 1,2,3 and mean across whole protocol.
Secondary outcome [12] 432210 0
Height
Timepoint [12] 432210 0
Height will be measured in antenatal clinic prior to recruitment to study and will be considered unchanged at time of experiment.

Eligibility
Key inclusion criteria
Pregnant people with uncomplicated pregnancies greater than or equal to 36 weeks’ gestation, BMI greater than or equal to 30 kg.m-2
Minimum age
18 Years
Maximum age
50 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Significant nasal pathology, severe systemic disease excluding obesity (as defined by an American Society of Anesthesiologists (ASA) physical status score of 4), preeclampsia of any degree, overwhelming sepsis, in labour or multiple pregnancy

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
To ensure allocation concealment is maintained, an investigator not involved in participant recruitment or the study protocol will place the preoxygenation sequence in a sealed opaque envelope (simulated preoxygenation with HFNO then face mask oxygen (even numbers) or simulated preoxygenation with face mask oxygen then HFNO (odd numbers), which will be accessed by the study investigator after enrolment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomly assigned in a 1:1 ratio in mixed blocks of four or eight, using computer-generated randomisation codes to HFNO preoxygenation first then FM preoxygenation (Group HFNO-FM) or FM preoxygenation first then HFNO preoxygenation (Group FM-HFNO).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
A sample of 100 pregnant people will be recruited. Using a power of 90% and a one-sided significance level of 0.025, the standard deviation of 9.09 from our previous study and a non-inferiority bound of 5% etO2 concentration, the required sample size is 70 participants. The non-inferiority margin is the same used in our previous study investigating a similar hypothesis in pregnant people (without specific BMI inclusion criterion). This margin is also the agreed upon value by the anaesthetic members of the study panel which would translate to clinical non-inferiority if achieved.

We anticipate a 30% drop-out rate including failed complete capture of first breath, thus the proposed sample size of 100. For participants in whom we fail at complete capture of first breath during their pregnant state experiment, their data will be excluded from analysis. As this is a different group to previous studies, we plan to perform an interim analysis when 70 participants have been recruited. This will allow for either early completion of the trial or application for extension of the sample size if the drop-out rate is lower or higher than anticipated.

As HFNO confers the additional safety benefit of effective apnoeic oxygenation (assuming no airway obstruction) with the ability to significantly prolong the safe apnoea period and face mask oxygen does not, this study has been designed as a non-inferiority trial. Based on the Consolidated Standards of Reporting Trials (CONSORT) statement, in a non-inferiority trial it is conventional to use a one-sided test, but with a stricter threshold for statistical significance (usually alpha is 0.025). If the new technique is worse than the comparator, the outcome will be the same as a two-sided test, but if the new technique is better than the comparator, the null hypothesis would not be rejected.

If there is truly no difference between the standard and experimental treatment, then 70 patients (or 70 data pairs) are required to be 90% sure that the lower limit of a one-sided 97.5% confidence interval (or equivalently a 95% two-sided confidence interval) will be above the non-inferiority limit of -5.

Mean differences, 95% confidence intervals (CI), and two-sided P values will be reported with a 0.05 alpha significance level. Strength of evidence statements will be used to describe P values: < 0.001 very strong evidence, 0.001 to < 0.01 strong evidence, 0.01 to 0.05 evidence, > 0.05 no evidence. The clinical significance of differences, where relevant, will be given.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/04/2024
Actual
23/04/2024
Date of last participant enrolment
Anticipated
30/06/2025
Actual
Date of last data collection
Anticipated
30/06/2025
Actual
Sample size
Target
100
Accrual to date
6
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 26820 0
The Royal Women's Hospital - Parkville
Recruitment postcode(s) [1] 42870 0
3052 - Parkville

Funding & Sponsors
Funding source category [1] 315713 0
Charities/Societies/Foundations
Name [1] 315713 0
Australian & New Zealand College of Anaesthetists Foundation
Country [1] 315713 0
Australia
Funding source category [2] 315717 0
Charities/Societies/Foundations
Name [2] 315717 0
Australian Society of Anaesthetists (ASA)
Country [2] 315717 0
Australia
Funding source category [3] 315947 0
Commercial sector/Industry
Name [3] 315947 0
Fisher & Paykel Heathcare
Country [3] 315947 0
New Zealand
Primary sponsor type
Individual
Name
Dr Patrick CF Tan
Address
Country
Australia
Secondary sponsor category [1] 318080 0
None
Name [1] 318080 0
Address [1] 318080 0
Country [1] 318080 0
Other collaborator category [1] 282968 0
Individual
Name [1] 282968 0
Prof Alicia T Dennis
Address [1] 282968 0
Country [1] 282968 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314578 0
The Royal Women's Hospital Human Research Ethics Committee
Ethics committee address [1] 314578 0
Ethics committee country [1] 314578 0
Australia
Date submitted for ethics approval [1] 314578 0
01/11/2023
Approval date [1] 314578 0
12/01/2024
Ethics approval number [1] 314578 0
23/40

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 132066 0
Dr Patrick CF Tan
Address 132066 0
Department of Anaesthesia, The Royal Women's Hospital 20 Flemington Road, Parkville VIC 3052
Country 132066 0
Australia
Phone 132066 0
+61 3 8345 2381
Fax 132066 0
Email 132066 0
[email protected]
Contact person for public queries
Name 132067 0
Patrick CF Tan
Address 132067 0
Department of Anaesthesia, The Royal Women's Hospital 20 Flemington Road, Parkville VIC 3052
Country 132067 0
Australia
Phone 132067 0
+61 3 8345 2381
Fax 132067 0
Email 132067 0
[email protected]
Contact person for scientific queries
Name 132068 0
Patrick CF Tan
Address 132068 0
Department of Anaesthesia, The Royal Women's Hospital 20 Flemington Road, Parkville VIC 3052
Country 132068 0
Australia
Phone 132068 0
+61 3 8345 2381
Fax 132068 0
Email 132068 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
individual participant data underlying published results only, after de-identification
When will data be available (start and end dates)?
Beginning 3 months following main results publication; no end date determined.
Available to whom?
case-by-case basis at the discretion of Primary Sponsor
Available for what types of analyses?
any purpose
How or where can data be obtained?
access subject to approvals by Principal Investigator. Email: [email protected]


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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