Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624001103550
Ethics application status
Approved
Date submitted
8/08/2024
Date registered
12/09/2024
Date last updated
12/09/2024
Date data sharing statement initially provided
12/09/2024
Type of registration
Retrospectively registered

Titles & IDs
Public title
Preoxygenation Using End-Tidal Oxygen for Rapid Sequence Intubation in the Emergency Department (The PREOXED Trial) - A Multicentre Stepped Wedge Cluster Randomised Control Trial
Scientific title
The Effect of Preoxygenation Using End-Tidal Oxygen on Incidence of Oxygen Desaturation for Rapid Sequence Intubation in the Emergency Department (The PREOXED Trial) - A Multicentre Stepped Wedge Cluster Randomised Control Trial
Secondary ID [1] 312718 0
Nil known
Universal Trial Number (UTN)
Trial acronym
PREOXED
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Critically ill 334740 0
Condition category
Condition code
Emergency medicine 331302 331302 0 0
Resuscitation
Anaesthesiology 331416 331416 0 0
Other anaesthesiology

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
For all patients involved in the study, the only intervention will be the use of End-tidal oxygen (ETO2) to guide preoxygenation. All aspects of rapid sequence intubation (RSI) will be at the discretion of the treating clinician including sedative/paralytic medications, positioning of the patient, preoxygenation method, intubation techniques and post-intubation sedation. Preoxygenation without the use of ETO2 is generally performed for a minimum of 3 minutes, however, with the use of ETO2 this may be performed earlier than 3 minutes if the correct ETO2 level has been reached.
Clinicians will be encouraged to aim for the highest ETO2 result possible with a goal of >85%. Clinicians will be able to view the ETO2 values and can decide on any changes to the preoxygenation techniques if deemed necessary. These techniques may include improved patient positioning, improved face mask seal, increased oxygen flow, length of preoxygenation time, or altering the preoxygenation device.

For hospitals in Sydney, the only additional equipment required for this study is the Philips™ IntelliVue G7m Gas Analyser Module 866173. This provides a non-dispersive infrared measurement of respiratory gases and a paramagnetic measurement of oxygen. The IntelliVue G7m Gas Analyser Module is designed to work with the IntelliVue patient monitors currently used in the EDs at the Sydney sites. At Lincoln Medical Center, the gas analyser used will be a Philips G5 gas analyser connected to a Philips Intellivue MP 70. At the University of New Mexico Medical Center, the Masimo root monitor is used.
The gas analysers produce display waves for O2 and CO2, together with numerics for end-tidal values for O2 and CO2 and to our knowledge, there are no differences in values between the various devices used.
The gas sampling occurs through a side-stream sampling tube at a rate of 200ml/min ±20 ml/min, which is either obtained from a nasal cannula in the spontaneously breathing patient or a sidestream line if connected to a BVM.

Data collection and adherence to the intervention will be monitored by research staff if available

Study design

The trial will be an international, multicentre, stepped-wedge randomised control trial on the implementation of ETO2 use in EDs for patients requiring RSI. A cluster will compose an individual hospital site and each site will serve as its own control with an implementation phase conducted at each site until all sites are recruited into the study period. To account for the differences in ED presentation rates at the various sites the cluster blocks will consist of patient numbers rather than a defined period of time. However, nearly all the sites will be recruiting at a similar rate, given that each site intubates 20-30 patients per month.

The trial will have 9 steps with 25 patients per step. Giving a total of 1400 patients (please see 'power calculation' in section 6.
Intervention code [1] 329241 0
Treatment: Devices
Intervention code [2] 329327 0
Treatment: Other
Comparator / control treatment
The control period includes a period whereby clinicians will not have access to ETO2 monitoring and routine RSI practices will be documented including all study variables. At all institutions, RSI is performed in a similar manner, utilising an airway checklist. There is no ‘standard operating procedure’ for RSI in any of the EDs and methods, therefore, vary depending on clinician preference and the condition of the patient, however, each site is a tertiary-level, university teaching hospital and therefore clinical practice is up to date and evidence-based. Standard preoxygenation methods in the Emergency department often consist of a bag-valve mask, with or without a PEEP valve, set at 15L/min, or the use of non-invasive ventilation or a non-rebreather mask, with or without a nasal cannula, set at 15 L/min or flush rate oxygen (>40 L/min). These methods depend on clinician preference and practice varies widely within each institution. As described in our previous studies the US sites have access to high-flow (>30L/min) oxygen. This is the only difference in the preoxygenation method, and we have found no significant difference in the mode of preoxygenation to patient desaturation rates or ETO2 levels among the different hospitals.

References
Caputo ND, Oliver M, West JR, Hackett R, Sakles JC. Use of End Tidal Oxygen Monitoring to Assess Preoxygenation During Rapid Sequence Intubation in the Emergency Department. Ann Emerg Med. 2019;74(3):410-5.

Oliver M, Caputo ND, West JR, Hackett R, Sakles JC. Emergency physician use of end-tidal oxygen monitoring for rapidsequence intubation. J Am Coll Emerg Physicians Open. 2020;1(5):706-13.
Control group
Active

Outcomes
Primary outcome [1] 339056 0
The primary objective of the study is the proportion of patients that experience oxygenation desaturation (SpO2 <93%, or >10% from baseline if SpO2 <93% at the end of preoxygenation) during the peri-intubation period
Timepoint [1] 339056 0
The peri-intubation period- the time when laryngoscope first enters the mouth to 2 minutes after the endotracheal tube [ETT] is confirmed on waveform capnography

The proportion of patients that experience oxygenation desaturation will be evaluated at the conclusion of the study
Secondary outcome [1] 438419 0
The secondary objective of the study is the lowest oxygen saturation (SpO2) during the peri-intubation period.
Timepoint [1] 438419 0
The peri-intubation period- the time when laryngoscope first enters the mouth to 2 minutes after the endotracheal tube [ETT] is confirmed on waveform capnography

Eligibility
Key inclusion criteria
1. The patient is located in the ED resuscitation bay of the participating centre.
2. The planned procedure is orotracheal intubation using a laryngoscope and RSI technique with preoxygenation for patients who are spontaneously breathing.
3. The patient is deemed to be at a high risk of hypoxia during RSI as per the treating ED clinician, as defined by:

- Any patient requiring any form of oxygen therapy before preoxygenation.
- Any patient with respiratory pathology based on clinical or radiological findings. Including, but not limited to:
o Pneumonia, pulmonary oedema, acute respiratory distress syndrome (ARDS), aspiration, pulmonary contusion from trauma, infective exacerbations of known lung disease (e.g. asthma, pulmonary fibrosis, emphysema) or pulmonary embolism (PE)
- Any patient with high oxygen consumption. Including, but not limited to:
o Sepsis, Diabetic ketoacidosis, alcohol or drug withdrawal, seizures, thyrotoxicosis
- Any underlying patient condition that may predispose to hypoxemia. Including, but not limited to:
o Obesity, pregnancy, underlying lung disease (e.g. asthma, pulmonary fibrosis, emphysema), severe injury- hypovolaemia/haemorrhage.
- or any other patient that the treating clinician has a high concern for hypoxemia during RSI.


Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patient is known to be less than 18 years old.
2. The patient has a supraglottic device in-situ e.g iGel or LMA.
3. The patient is known to be pregnant.
4. The patient is known to be a prisoner.
5. The patient was intubated in the prehospital environment.
6. Immediate need for tracheal intubation precludes preoxygenation i.e. the patient is in cardiac arrest.

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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
Other
Other design features
Multicentre Stepped Wedge Cluster Randomised Control Trial
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
The primary analysis will be an unadjusted, intention-to-treat comparison of patients who received ETO2 use during the study period in comparison with the group of patients not receiving ETO2 use during the control period regarding the primary outcome. The difference between the two study groups will be compared using a Generalised Linear Mixed Model to estimate the effect sizes for the binary outcomes.

Power Calculation

To power this study, we utilised the assistance of a biostatistician. Utilising the calculations based on Hemming et al. and based on the plan to recruit 9 hospital sites with 8 clusters and 9 steps each site we calculated that 1232 (17 patients per step) patients would be required to achieve a power of 80% with a significance of 0.05 to detect an absolute difference of 10% in the rate of desaturation. Factoring in a missing data rate of approx. 14-15% this gives a total of 1400 patients required (22 patients per step). The intracluster correlation (ICC) was calculated at 0.01 given that we believe that the ICC is likely to be small based on our previous studies.(12) The proportion of patients in the control arm meeting the primary outcome (desaturation <93%) was calculated at 20%. This is based on current audit data from the Australia and New Zealand ED airway registry (ANZEDAR) demonstrating a desaturation rate of 20% for patients undergoing RSI with respiratory pathology.
The proportion of patients in the intervention arm meeting the primary outcome was calculated at 10%, i.e. an absolute difference of 10% in desaturation rates between the control and intervention arms of the study. This was based on our previous study(9) demonstrating a desaturation rate of 10% in the intervention group and also based on a clinically meaningful difference of 10% between the two groups.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
1/08/2024
Date of last participant enrolment
Anticipated
31/12/2025
Actual
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
1400
Accrual to date
4
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 26911 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 26912 0
Westmead Hospital - Westmead
Recruitment hospital [3] 26913 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [4] 26914 0
The Northern Beaches Hospital - Frenchs Forest
Recruitment hospital [5] 26915 0
The Alfred - Melbourne
Recruitment hospital [6] 26916 0
Liverpool Hospital - Liverpool
Recruitment postcode(s) [1] 42975 0
2050 - Camperdown
Recruitment postcode(s) [2] 42976 0
2145 - Westmead
Recruitment postcode(s) [3] 42977 0
2065 - St Leonards
Recruitment postcode(s) [4] 42978 0
2086 - Frenchs Forest
Recruitment postcode(s) [5] 42979 0
3004 - Melbourne
Recruitment postcode(s) [6] 42980 0
2170 - Liverpool
Recruitment outside Australia
Country [1] 26498 0
United States of America
State/province [1] 26498 0
New York, New Mexico, Minneapolis

Funding & Sponsors
Funding source category [1] 317147 0
Charities/Societies/Foundations
Name [1] 317147 0
The Greenlight institute, Hearts and Minds Institute
Country [1] 317147 0
Australia
Primary sponsor type
Government body
Name
Sydney Local Health District
Address
Country
Australia
Secondary sponsor category [1] 319415 0
None
Name [1] 319415 0
none
Address [1] 319415 0
Country [1] 319415 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315898 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 315898 0
Ethics committee country [1] 315898 0
Australia
Date submitted for ethics approval [1] 315898 0
Approval date [1] 315898 0
22/03/2024
Ethics approval number [1] 315898 0
X23-0503 & 2023/ETH02801

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

Contacts
Principal investigator
Name 136142 0
Dr Matthew Oliver
Address 136142 0
Emergency Department, Royal Prince Alfred Hospital, Missenden Road, Camperdown, Sydney, NSW, 2050
Country 136142 0
Australia
Phone 136142 0
+61 02 9515 0017
Fax 136142 0
Email 136142 0
[email protected]
Contact person for public queries
Name 136143 0
Naomi Derrick
Address 136143 0
The Greenlight Institute, Royal Prince Alfred Hospital, Missenden Road, Camperdown, Sydney, NSW, 2050
Country 136143 0
Australia
Phone 136143 0
+61 457 240478
Fax 136143 0
Email 136143 0
[email protected]
Contact person for scientific queries
Name 136144 0
Naomi Derrick
Address 136144 0
The Greenlight Institute, Royal Prince Alfred Hospital, Missenden Road, Camperdown, Sydney, NSW, 2050
Country 136144 0
Australia
Phone 136144 0
+61 457 240478
Fax 136144 0
Email 136144 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?
Following publication, individual de-identified patient data will be made available for sharing to researchers with 1) a signed data access agreement, 2) research testing a hypothesis, 3) a protocol that has been approved by an institutional review board, and 4) a proposal that has received approval from the principal investigator.
When will data be available (start and end dates)?
From publication to no end date
Available to whom?
Researchers with:
A signed data access agreement research testing a hypothesis
A protocol that has been approved by an institutional review board/Ethics department
A proposal that has received approval from the principal investigator
Available for what types of analyses?
Meta-analyses
How or where can data be obtained?
Via the chief investigator (Matthew Oliver)


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
24084Study protocol    388271-(Uploaded-08-08-2024-13-47-26)-The PREOXED Trial- Protocol v12.pdf



Results publications and other study-related documents

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