Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624001117505
Ethics application status
Approved
Date submitted
28/08/2024
Date registered
17/09/2024
Date last updated
17/09/2024
Date data sharing statement initially provided
17/09/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Penthrox vs nitrous oxide for painful emergency medicine procedures
Scientific title
A randomised controlled trial comparing Penthrox (methoxyflurane) with nitrous oxide for analgesia during painful emergency medicine procedures in patients aged eight years and over
Secondary ID [1] 312805 0
Nil known
Universal Trial Number (UTN)
U1111-1312-3668
Trial acronym
N/A
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
Painful emergency medicine procedures 334870 0
Condition category
Condition code
Emergency medicine 331423 331423 0 0
Other emergency care
Anaesthesiology 331543 331543 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This trial will examine the effectiveness of Penthrox (methoxyflurane; intervention) versus nitrous oxide (comparator) in emergency department patients undergoing painful procedures. Participants randomised to the Penthrox arm will be asked to inhale and exhale into the mouthpiece of a 3mL Penthrox device for 6–8 breaths, beginning inhalation thirty seconds before commencement of the procedure, after which they can continue to inhale continuously or intermittently as required for the duration of the procedure while under observation by the clinician researcher. A second 3mL bottle may be used for continued analgesia if deemed necessary by the clinician researcher.
Intervention code [1] 329342 0
Treatment: Drugs
Comparator / control treatment
Nitrous oxide is a staple of pain relief in the emergency department, administered via a disposable plastic circuit connected to a gas supply outlet in dedicated treatment rooms. Participants randomised to the nitrous oxide arm will begin receiving treatment thirty seconds before commencement of the procedure, during which time nitrous oxide will be titrated up to a maximum concentration of 70%, delivered via a facemask or mouthpiece. The concentration may be adjusted for analgesic effect as required throughout the duration of the procedure, after which it will be discontinued and the participant will be administered 100% oxygen for a brief (~30 second) period before they return to breathing room air.
Control group
Active

Outcomes
Primary outcome [1] 339177 0
Patient-reported average pain intensity during the procedure (based on individual measurements taken at the timepoints specified below)
Timepoint [1] 339177 0
1. Immediately pre-procedure
2. Immediately post-procedure
3. 5 minutes post-procedure
4. 10 minutes post-procedure.
Secondary outcome [1] 438946 0
Patient-reported worst pain intensity during the procedure (based on individual measurements taken at the timepoints specified below)
Timepoint [1] 438946 0
1. Immediately pre-procedure
2. Immediately post-procedure
3. 5 minutes post-procedure
4. 10 minutes post-procedure.
Secondary outcome [2] 438947 0
Patient reported current pain intensity before and after the procedure
Timepoint [2] 438947 0
1. Immediately pre-procedure
2. Immediately post-procedure
3. 5 minutes post-procedure
4. 10 minutes post-procedure.
Secondary outcome [3] 438948 0
Patient-reported procedure satisfaction
Timepoint [3] 438948 0
Ten minutes after procedure
Secondary outcome [4] 438949 0
Clinician-reported patient pain intensity during the procedure
Timepoint [4] 438949 0
Immediately after procedure
Secondary outcome [5] 438950 0
Clinician-reported procedure satisfaction
Timepoint [5] 438950 0
Immediately after procedure
Secondary outcome [6] 438951 0
Time to procedure
Timepoint [6] 438951 0
Assessed following discharge
Secondary outcome [7] 438952 0
Time to discharge
Timepoint [7] 438952 0
Assessed following discharge
Secondary outcome [8] 438953 0
Use of adjunct analgesia
Timepoint [8] 438953 0
Following discharge
Secondary outcome [9] 438954 0
Adverse events (e.g. for Penthrox: dizziness, feeling sick or nauseous, drowsiness, headache, feeling drunk; for nitrous oxide: feeling dizzy or light-headed, feeling or being sick, euphoria, feeling sleepy, feeling bloated).
Timepoint [9] 438954 0
Following discharge

Eligibility
Key inclusion criteria
• Age of eight years or older
• Attending Box Hill Hospital’s Emergency Department Fast Track area
• Requiring a potentially painful procedure that would normally involve the use of nitrous oxide
• Trained clinician researcher available to enrol patient, administer either medication, and instruct/assist participants with self-administration of Penthrox where necessary.
Minimum age
8 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Inability to self-administer Penthrox
• Inability to give verbal or written consent.

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 will be concealed through the use of computerised randomisation, the schedule for which is described in detail below. A team member without contact with patients will obtain and employ the randomisation schedule (creating sequentially numbered, opaque, sealed envelopes).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patients will be randomly assigned (1:1) using block randomisation with random block lengths (between 2 and 6 per block) to either intervention or comparator. The randomisation schedule will be developed using the ‘blockrand’ package in R (v4.3.3; R Core Team, Vienna, Austria).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
For patient-reported pain intensity (numerical rating scale), if there is truly no difference between Penthrox and nitrous oxide, 198 patients (99 per group) are required to be 80% 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 -1.4 points assuming a conservative SD of 3.5 points. There is no plan to achieve an equal balance of adult and child participants in the sample; our aim is for a broad enrolment pool that represents real-world use of procedural sedation.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
18/09/2024
Actual
Date of last participant enrolment
Anticipated
9/09/2026
Actual
Date of last data collection
Anticipated
31/12/2026
Actual
Sample size
Target
198
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 26975 0
Box Hill Hospital - Box Hill
Recruitment postcode(s) [1] 43050 0
3128 - Box Hill

Funding & Sponsors
Funding source category [1] 317239 0
Charities/Societies/Foundations
Name [1] 317239 0
Eastern Health Foundation
Country [1] 317239 0
Australia
Primary sponsor type
Other
Name
Eastern Health
Address
Country
Australia
Secondary sponsor category [1] 319520 0
None
Name [1] 319520 0
Address [1] 319520 0
Country [1] 319520 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315977 0
Eastern Health Human Research Ethics Committee
Ethics committee address [1] 315977 0
Ethics committee country [1] 315977 0
Australia
Date submitted for ethics approval [1] 315977 0
03/04/2024
Approval date [1] 315977 0
31/07/2024
Ethics approval number [1] 315977 0
E24-007-106072

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

Contacts
Principal investigator
Name 136402 0
A/Prof Paul Buntine
Address 136402 0
Eastern Health – Box Hill Hospital, Emergency Department, 5 Arnold St, Box Hill VIC 3128.
Country 136402 0
Australia
Phone 136402 0
+61 425 749 936
Fax 136402 0
Email 136402 0
[email protected]
Contact person for public queries
Name 136403 0
Paul Buntine
Address 136403 0
Eastern Health – Box Hill Hospital, Emergency Department, 5 Arnold St, Box Hill VIC 3128.
Country 136403 0
Australia
Phone 136403 0
+61 425 749 936
Fax 136403 0
Email 136403 0
[email protected]
Contact person for scientific queries
Name 136404 0
Paul Buntine
Address 136404 0
Eastern Health – Box Hill Hospital, Emergency Department, 5 Arnold St, Box Hill VIC 3128.
Country 136404 0
Australia
Phone 136404 0
+61 425 749 936
Fax 136404 0
Email 136404 0
[email protected]

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?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
24136Ethical approval    388336-(Uploaded-23-08-2024-13-03-47)-HREC E24-007-106072 Final Approval Jul2024.pdf



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.