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Trial registered on ANZCTR


Registration number
ACTRN12623000936628
Ethics application status
Approved
Date submitted
4/08/2023
Date registered
30/08/2023
Date last updated
30/08/2024
Date data sharing statement initially provided
30/08/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Self-administered inhaled methoxyflurane (Penthrox®) as pre-injection analgesia in Podiatry Outpatients: A blinded, randomised study.
Scientific title
Efficacy of self-administered inhaled methoxyflurane (Penthrox®) as pre-injection analgesia in Podiatry Outpatients: A blinded, randomised study.
Secondary ID [1] 310261 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
pain 330941 0
Condition category
Condition code
Anaesthesiology 327748 327748 0 0
Pain management
Public Health 327993 327993 0 0
Health service research

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Self-administered inhaled methoxyflurane (via a hand-held Penthrox inhaler) as pre-injection analgesia.
Once off dose: 3mL methoxyflurane 99.9% inhalation solution.
Participants will be instructed to inhale and exhale through the mouthpiece of the inhaler. If a higher concentration of analgesia is required, the participant will be instructed to occlude the diluter hole with their finger.
Duration: The participant will be instructed to take 6 slow breaths through the inhaler before the local anaesthetic is administered. The participant may then take additional breaths as required while the local anaesthetic is being administered. (Approx 5 minutes). Once the local anaesthetic has been administered, the inhaler will be removed from the participant and disposed of accordingly. The participant will be closely monitored by a Registered Nurse who record observations including oxygen saturation, heart rate, respiratory rate, sedation score, adverse events and ensure the inhaler is used as instructed.
Intervention code [1] 326664 0
Treatment: Drugs
Comparator / control treatment
placebo inhaler. This will take the form of a Penthrox inhaler where no methoxyflurane has been decanted into it. Instead 3 drops of methoxyflurane will be added to the wrist strap to give a similar smell to the intervention inhaler.
Control group
Placebo

Outcomes
Primary outcome [1] 335639 0
Verbal Numerical Pain Rating Score (VNPRS) (10-point scale from 0 to 10, where 0 is no pain at all and 10 is worst pain imaginable).
Timepoint [1] 335639 0
Worst pain experienced during the procedure (includes local anaesthetic administration and toenail surgery). This will be recorded 1 hour following the use of the intervention/placebo inhaler to allow the effects of the methoxyflurane to wear off as to not impact on the participant's cognition.
Secondary outcome [1] 425027 0
Verbal Numerical Anxiety Rating Score (VNARS) (10-point scale from 0-10, where 0 is no anxiety and 10 is extreme anxiety).
Timepoint [1] 425027 0
Baseline, and immediately following administration of local anaesthetic.
Secondary outcome [2] 425028 0
patient satisfaction (7-point Likert scale from ‘extremely dissatisfied’ to ‘extremely satisfied’)
Timepoint [2] 425028 0
1 hour following the use of the intervention/placebo inhaler to allow the effects of the methoxyflurane to wear off.

Eligibility
Key inclusion criteria
o 18 years of age and over
o A painful ingrown toenail which requires a minor surgical procedure
o Ability to self-administer methoxyflurane via a hand-held Penthrox® inhaler.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
o A documented history of cognitive impairment or are otherwise unable to give informed consent
o Allergy to methoxyflurane or any other medication or agent required for the procedure
o A personal or familial history of malignant hyperthermia
o Previous history of a significant head injury
o Significant renal impairment (eGFR<60mL/min)
o Significant cardiac or respiratory illnesses
o Women who are pregnant, planning to become pregnant or breastfeeding
o Patients taking concurrent drugs with known clinically significant nephrotoxic effects (patients taking tetracyclines, aminoglycosides, colistin, amphotericin B, barbiturates, alcohol, isoniazid and rifampicin will be excluded).
o Patients who have received methoxyflurane on the day prior to the procedure or 15 mL (5 bottles) in the week prior to the procedure.
o Neurological Assessment: Absent protective sensation upon monofilament testing.
o Vascular Assessment: Clinically significant Peripheral Arterial Disease.
o Patients who are not willing or able to fast for 6 hours prior to the planned procedure.

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)
central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomised to either active treatment with methoxyflurane or placebo in a 50:50 ratio in four blocks of 10 participants (i.e. within every 10 sequentially recruited participants, 5 will be randomised to treatment), to increase the likelihood of equal randomisation even in the unlikely event of incomplete recruitment. A randomisation code will be prepared by the PI using an online random number generator before recruitment commences.

Participant randomisation will occur on the day of the procedure, thus drop-outs are unlikely. However, if a participant withdraws after the medication has been administered, but before completing the post-procedure data collection processes, the ‘intention to treat’ analysis method will be used.
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
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
Based on detecting an absolute difference of 3 on the verbal numerical rating pain scale (VNRPS) assuming a standard deviation of 3 we estimated that 32 patients (16 in each arm) were required to achieve 80% power with a type-1 error probability (a)=0.05. We increased this to 40 participants (20 in each arm) to allow for 10% loss to follow up and 2.5% crossover in each study arm.

The primary outcome for the study is the worst pain experienced during the procedure. It will be assessed at 1 hour following completion of the surgical procedure. The pain will be assessed using a verbal numerical ranking score ranging from 0 (representing no pain) to 10 (representing the worst pain imaginable).

A Shapiro-Wilk test will be implemented prior to conducting the analysis. In the event of a non-significant test for normality (SW p=0.05) the outcome will be analysed using a 2-sample t-test using 2-sided hypothesis testing. This assumes the observed pain scores were sampled from a normally distributed population. A SW p-value <0.05 will be considered statistically significant. In this instance the primary outcome will be analysed using a Wilcoxon rank-sum test, which does not assume an underlying normally distributed pain scores in the population being sampled.

Irrespective of the inferential test selected, the magnitude of effect will be expressed as both an absolute and relative difference in mean pain scores between the two groups.

All analyses will be undertaken following imputation of missing data.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/09/2023
Actual
8/11/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
40
Accrual to date
4
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 314469 0
Charities/Societies/Foundations
Name [1] 314469 0
Flinders Foundation
Country [1] 314469 0
Australia
Funding source category [2] 314509 0
Charities/Societies/Foundations
Name [2] 314509 0
The Hospital Research Foundation Group
Country [2] 314509 0
Australia
Primary sponsor type
Individual
Name
Claire Huxtable
Address
Noarlunga Health Service
30 Alexander Kelly Drive, Noarlunga Centre SA 5168
Country
Australia
Secondary sponsor category [1] 316454 0
Government body
Name [1] 316454 0
Southern Adelaide Local Health Network
Address [1] 316454 0
Noarlunga Health Service
30 Alexander Kelly Drive, Noarlunga Centre SA 5168
Country [1] 316454 0
Australia
Secondary sponsor category [2] 316455 0
University
Name [2] 316455 0
UniSA
Address [2] 316455 0
City East University of South Australia GPO Box 2471. Adelaide SA 5001
Country [2] 316455 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313520 0
Southern Adelaide Clinical Human Research Ethics Committee
Ethics committee address [1] 313520 0
Ethics committee country [1] 313520 0
Australia
Date submitted for ethics approval [1] 313520 0
19/05/2023
Approval date [1] 313520 0
13/10/2023
Ethics approval number [1] 313520 0
Ethics committee name [2] 313552 0
UniSA Human Research Ethics Committee
Ethics committee address [2] 313552 0
Ethics committee country [2] 313552 0
Australia
Date submitted for ethics approval [2] 313552 0
18/08/2023
Approval date [2] 313552 0
Ethics approval number [2] 313552 0

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

Contacts
Principal investigator
Name 128426 0
Ms Claire Huxtable
Address 128426 0
Noarlunga Health Service
30 Alexander Kelly Drive, Noarlunga Centre SA 5168
Country 128426 0
Australia
Phone 128426 0
+61430520109
Fax 128426 0
Email 128426 0
[email protected]
Contact person for public queries
Name 128427 0
Claire Huxtable
Address 128427 0
Noarlunga Health Service
30 Alexander Kelly Drive, Noarlunga Centre SA 5168
Country 128427 0
Australia
Phone 128427 0
+61430520109
Fax 128427 0
Email 128427 0
[email protected]
Contact person for scientific queries
Name 128428 0
Claire Huxtable
Address 128428 0
Noarlunga Health Service
30 Alexander Kelly Drive, Noarlunga Centre SA 5168
Country 128428 0
Australia
Phone 128428 0
+61430520109
Fax 128428 0
Email 128428 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?

No Supporting Document Provided



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.