Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000551796
Ethics application status
Approved
Date submitted
8/03/2022
Date registered
8/04/2022
Date last updated
11/08/2024
Date data sharing statement initially provided
8/04/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
High flow humidified nasal Oxygen to PrEvent desaturation FOR labouring people using remifentanil PCA (The HOPE-for-REMI study)
Scientific title
High flow humidified nasal oxygen for prevention of hypoxaemia associated with remifentanil patient controlled analgesia (PCA) in labouring people – a safety and feasibility study
Secondary ID [1] 305232 0
None
Universal Trial Number (UTN)
U1111-1269-0495
Trial acronym
HOPE-for-REMI
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pregnancy 325351 0
Pain relief 325352 0
Condition category
Condition code
Anaesthesiology 322734 322734 0 0
Anaesthetics
Anaesthesiology 322735 322735 0 0
Pain management
Respiratory 322736 322736 0 0
Normal development and function of the respiratory system
Reproductive Health and Childbirth 323249 323249 0 0
Childbirth and postnatal care

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study period will be two hours from the commencement of Remifentanil PCA. A member of the investigator team will be present in-person with the participant for the entire duration. All study interventions (Remifentanil PCA, high flow nasal oxygen/standard care nasal oxygen) will cease at the end of the two hours. Adherence to protocols will be assessed and recorded by direct observation by investigator.

Remifentanil PCA administration protocol
Remifentanil will be drawn up by an investigator and double checked with a qualified member of staff (eg. anaesthetist, anaesthetic accredited fellow/registrar, registered nurse, midwife). Two milligrams of remifentanil will be diluted into 50 ml of 0.9% normal saline to final concentration of 40 microgram/ml. The drug syringe will then be loaded into a pre-programmed PCA pump which will be set to a remifentanil PCA protocol which will deliver 40 microgram (or 1 ml) when triggered with a two minute lockout. This administration protocol is the same one used in the RESPITE trial. We think it is important to mirror the practice of the most comprehensive remifentanil PCA trial to date so as to be able to compare secondary outcomes and maximise potential clinical applicability.

If the participant already has a peripheral intravenous cannula (20 gauge or larger) inserted, the cannula placement and patency will be checked with a manual hand flush of 10 ml of 0.9% normal saline and a check of good flow of intravenous crystalloid fluid through the line will be confirmed. If the participant does not have a peripheral intravenous cannula (20 gauge or larger) inserted, one will be placed and checked in the same manner as above post-insertion.

The intravenous fluid will be set to a constant flow rate as a baseline to prevent drug accumulation in the line. The remifentanil syringe will be connected via extension tubing to the anti-reflux injection port closest to the participant. The PCA trigger button will be given to the participant with instructions to press the button at the earliest point during a contraction.

The participant will be monitored continuously by a study investigator and a desaturation episode will be declared if her oxygen saturation falls to 94% or less. If this occurs, the attending investigator will rouse the participant verbally and ask them to take a breath. The remifentanil PCA will be removed from the participant’s reach. If the participant remains apnoeic, the attending investigator will attempt to rouse the participant physically by trapezius squeeze. If the participant remains apnoeic and oxygen saturation levels continue to fall, rescue breaths will be administered via a Laerdal bag valve mask running at 15 litres/min of supplemental oxygen by trained investigator. After safe oxygen saturation levels have been re-established, any desaturation episode will trigger the commencement of the corresponding oxygen protocol.

Intervention group
High flow humidified nasal oxygen group protocol
High flow humidified nasal oxygen will be applied via the Airvo 2 (Fisher & Paykel, New Zealand) machine. It will be commenced at a flow of 30 litres/min and an inspired fraction of oxygen of 60%. The comfort scale questionnaire will be asked at this flow rate. The flow rate will then be increased to 40 litres/min for 5 minutes and then 50 litres/min with the comfort scale questionnaire asked after each adjustment. The flow rate will be decreased by 10 litres/min if the participant complains of discomfort to a minimum of 30 litres/min after which the study protocol will be abandoned.

The inspired fraction of oxygen of 60% has be chosen because this is the concentration that was studied by Khaw et al when investigating the effects of maternal supplemental oxygen on the fetus. In their prospective double-blinded trial, they showed no difference in neonatal outcomes and levels of lipid peroxidation between groups of mothers receiving supplemental oxygen versus room air during caesarean section. This provides us with a starting point which we can be assured is safe. We expect that the average required inspired fraction of oxygen required to prevent desaturation will be lower than this.
Intervention code [1] 322915 0
Treatment: Devices
Comparator / control treatment
Same Remifentanil PCA administration protocol as intervention group.

Control Group
Standard care nasal oxygen group protocol
Standard (low flow) nasal cannulae will be applied. It will be commenced at a flow of 4 litres/min. The comfort scale questionnaire will be asked at this flow rate. The flow rate will remain at this level for the duration of the protocol as any increases may risk drying of the nasal mucosa and nose bleeds (epistaxis). This is particularly pertinent because the pregnant population experiences increased nasal vascularity and mucosal congestion which increases their baseline risk of epistaxis. The flow rate will be decreased to 2 litres/min if the participant complains of discomfort after which the study protocol will be abandoned if further discomfort reported.
Control group
Active

Outcomes
Primary outcome [1] 330685 0
Oxygen saturation less than or equal to 94%.
Oxygen saturations and oxygen reserve index will be measured using a Masimo Radical-7 touch pulse co-oximeter.
Timepoint [1] 330685 0
Oxygen saturation will be measured continuously throughout protocol. Saturation less than 94% will be considered a desaturation episode at which time the lowest recorded saturation value and duration of desaturation will be recorded.
Primary outcome [2] 330686 0
Heart rate less than 40 beats per minute. This will be measured using a Masimo Radical-7 touch pulse co-oximeter.
Timepoint [2] 330686 0
Heart rate will be measured continuously throughout protocol.
Primary outcome [3] 330688 0
Oxygen reserve index. Oxygen saturations and oxygen reserve index will be measured using a Masimo Radical-7 touch pulse co-oximeter.
Timepoint [3] 330688 0
Oxygen reserve index will be measured continuously throughout protocol. It will be specifically recorded one minute, 30 seconds and 10 seconds prior to any desaturation episode (oxygen saturation less than or equal to 94%)
Secondary outcome [1] 407213 0
Chest wall rigidity
A member of the investigator team will be present in-person with the participant for the entire duration. This outcome will occur via verbal report to the investigator.
Timepoint [1] 407213 0
Participants will be asked to report this symptom if occurs at any timepoint during study protocol.
Secondary outcome [2] 407214 0
Epistaxis.
A member of the investigator team will be present in-person with the participant for the entire duration. This outcome will occur via verbal report to the investigator.
Timepoint [2] 407214 0
Participants will be asked to report this symptom if occurs at any timepoint during study protocol.
Secondary outcome [3] 407215 0
Blood pressure measured using automatic blood pressure cuff on Masimo Radical-7 monitor
Timepoint [3] 407215 0
Blood pressure will be measured at 5 minutes and 10 minutes followed by 10 minutely intervals during study protocol.
Secondary outcome [4] 407216 0
Respiratory rate. Measured using acoustic respiratory rate monitoring on Masimo Radical-7 monitor
Timepoint [4] 407216 0
Respiratory rate will be recorded at 5 minutes and 10minutes followed by 10 minutely intervals during study protocol.
Secondary outcome [5] 407217 0
Comfort scores will be measured using a 5 point word associated scale for comfort levels
Timepoint [5] 407217 0
At commencement of either high flow or standard nasal oxygen. Then measured with flow rate change from 30 to 40 and 40 to 50 litres/min for high flow nasal oxygen OR from 4 to 2 litres/min for standard nasal oxygen.
Secondary outcome [6] 407218 0
Pain score. Measured using a 10 point verbal pain score.
Timepoint [6] 407218 0
During a contraction - before remifentanil PCA starts then at 5, 10, 30. 60, 90, 120 minutes after remifentanil PCA started.
Secondary outcome [7] 407219 0
Satisfaction score will be measured using a 5 point word associated scale for comfort levels
Timepoint [7] 407219 0
Before remifentanil PCA starts then at 5, 10, 30. 60, 90, 120 minutes after remifentanil PCA started.
Secondary outcome [8] 407220 0
Remifentanil PCA dose demands
A member of the investigator team will be present in-person with the participant for the entire duration. This outcome will be recorded from the digital display on the PCA pump.
Timepoint [8] 407220 0
At 5 minutes and 10minutes followed by 10 minutely intervals during study protocol.
Secondary outcome [9] 407221 0
Remifentanil dose administrations
A member of the investigator team will be present in-person with the participant for the entire duration. This outcome will be recorded from the digital display on the PCA pump.
Timepoint [9] 407221 0
At 5 minutes and 10minutes followed by 10 minutely intervals during study protocol.
Secondary outcome [10] 435134 0
Neonatal APGAR score to assess newborn health
Timepoint [10] 435134 0
Secondary outcome [11] 435135 0
Neonatal APGAR score to assess newborn health
Timepoint [11] 435135 0
At 5 minutes post-delivery
Secondary outcome [12] 435136 0
Requirement for neonatal resuscitation. Data obtained from medical records.
Timepoint [12] 435136 0
At 5 minutes post-delivery
Secondary outcome [13] 435137 0
Requirement for neonatal resuscitation. Data obtained from medical records.
Timepoint [13] 435137 0
First 10 minutes after delivery
Secondary outcome [14] 435138 0
Neonatal admission to special care or neonatal intensive care. Data obtained from medical records.
Timepoint [14] 435138 0
First 10 minutes after delivery
Secondary outcome [15] 435139 0
Neonatal admission to special care or neonatal intensive care. Data obtained from medical records.
Timepoint [15] 435139 0
First 24 hours after delivery
Secondary outcome [16] 435140 0
Requirement for interventional delivery due to fetal distress. Data obtained from medical records.
Timepoint [16] 435140 0
First 24 hours after delivery
Secondary outcome [17] 435141 0
Requirement for interventional delivery due to fetal distress. Data obtained from medical records.
Timepoint [17] 435141 0
Any point during labour
Secondary outcome [18] 435142 0
Fetal heart rate during maternal desaturation obtained via cardiotocograph reading.
Timepoint [18] 435142 0
Any point during labour
Secondary outcome [19] 435143 0
Fetal heart rate during maternal desaturation obtained via cardiotocograph reading.
Timepoint [19] 435143 0
Continuous during a maternal desaturation episode - lowest value

Eligibility
Key inclusion criteria
People (20 in each group) in labour, expecting live birth, term pregnancy more than or equal to 37 weeks gestation, singleton pregnancy, no cardiac or respiratory disease, no previous caesarean section
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Second stage of labour, significant nasal pathology, severe systemic disease (American Society of Anesthesiologists (ASA) physical status score of 3 or more), preeclampsia or sepsis, opioid allergy, inability to understand protocol instructions, substance abuse disorder, any administration of intramuscular opioid in the last 24 hours

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)
An investigator not involved in participant recruitment or the study protocol will place the group allocation in a sealed opaque envelope
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation with a computer-generated random number sequence will be used
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
On the day of recruitment, at the time of analgesia request, the women will be randomised by an investigator to either standard care nasal oxygen or HFNO. Both groups will be monitored in the same manner and receive the same remifentanil PCA protocol.
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Two key aims are to determine the endpoint of incidence of oxygen desaturation in the control group and proportion of participants that can wear HFNO for the study period representing acceptability. The first of these aims can be determined from the control group and the second can be determined from the intervention group. However, in order to answer feasibility questions and obtain a point difference to calculate a sample size for a larger trial, we need to conduct a RCT.

As per Moore et al[48], when conducting a trial with two independent groups with a continuous outcome (in this case, incidence of oxygen desaturation less than or equal to 94%) we have based a sample size calculation on a hypothesized intervention group incidence of oxygen desaturation. We believe a clinically meaningful reduction in the incidence of oxygen desaturation from 70% to a third of that value, that is 23%, would indicate that the intervention (HFNO) is effective. With type-1 error rate of 0.05 and a type-2 error rate of 0.1, the calculated sample size is 38 participants (19 in each group). We think a sample of 40 women (20 in each group) should be adequate to inform us on other safety and feasibility aims as well.

Statistical analysis will be performed with the assistance of the Statistical Consulting Centre and Melbourne Statistical Consulting Platform at the School of Mathematics and Statistics, The University of Melbourne.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
31/07/2024
Actual
6/08/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
40
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 21792 0
The Royal Women's Hospital - Parkville
Recruitment postcode(s) [1] 36849 0
3052 - Parkville

Funding & Sponsors
Funding source category [1] 309608 0
Charities/Societies/Foundations
Name [1] 309608 0
Australia and New Zealand College of Anaesthetists (ANZCA)
Country [1] 309608 0
Australia
Primary sponsor type
Hospital
Name
Department of Anaesthesia, The Royal Women's Hospital - Parkville
Address
20 Flemington Road, Parkville VIC 3052
Country
Australia
Secondary sponsor category [1] 310622 0
None
Name [1] 310622 0
Address [1] 310622 0
Country [1] 310622 0
Other collaborator category [1] 282189 0
Individual
Name [1] 282189 0
Prof Alicia Dennis
Address [1] 282189 0
Department of Anaesthesia, The Royal Women's Hospital
20 Flemington Road, Parkville VIC 3052
Country [1] 282189 0
Australia
Other collaborator category [2] 282190 0
Individual
Name [2] 282190 0
Prof Philip Peyton
Address [2] 282190 0
Department of Anaesthesia, Austin Health
Studley Road Heidelberg VIC 3084
Country [2] 282190 0
Australia
Other collaborator category [3] 282191 0
Individual
Name [3] 282191 0
Dr Julia Unterscheider
Address [3] 282191 0
Department of Maternity services
Royal Women’s Hospital
20 Flemington Road, Parkville VIC 3052
Country [3] 282191 0
Australia
Other collaborator category [4] 282192 0
Individual
Name [4] 282192 0
Dr Adam Deane
Address [4] 282192 0
Intensive Care Unit, The Royal Melbourne Hospital – City Campus
Grattan Street, Parkville VIC 3050
Country [4] 282192 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309382 0
Royal Women's Hospital Human Research Ethics Committee
Ethics committee address [1] 309382 0
Ethics committee country [1] 309382 0
Australia
Date submitted for ethics approval [1] 309382 0
07/09/2021
Approval date [1] 309382 0
23/11/2021
Ethics approval number [1] 309382 0
21/48

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

Contacts
Principal investigator
Name 113962 0
Dr Patrick CF Tan
Address 113962 0
Department of Anaesthesia, The Royal Women's Hospital
20 Flemington Road, Parkville VIC 3052
Country 113962 0
Australia
Phone 113962 0
+61 3 8345 2381
Fax 113962 0
+61 3 83452379
Email 113962 0
[email protected]
Contact person for public queries
Name 113963 0
Patrick CF Tan
Address 113963 0
Department of Anaesthesia, The Royal Women's Hospital
20 Flemington Road, Parkville VIC 3052
Country 113963 0
Australia
Phone 113963 0
+61 3 8345 2381
Fax 113963 0
+61 3 83452379
Email 113963 0
[email protected]
Contact person for scientific queries
Name 113964 0
Patrick CF Tan
Address 113964 0
Department of Anaesthesia, The Royal Women's Hospital
20 Flemington Road, Parkville VIC 3052
Country 113964 0
Australia
Phone 113964 0
+61 3 8345 2381
Fax 113964 0
+61 3 83452379
Email 113964 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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No documents have been uploaded by study researchers.

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