Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000936628p
Ethics application status
Submitted, not yet approved
Date submitted
4/08/2023
Date registered
30/08/2023
Date last updated
30/08/2023
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
Scientific title
Efficacy of self-administered inhaled methoxyflurane (Penthrox®) as pre-injection analgesia in Podiatry Outpatients
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
Baseline and worst pain experienced during the procedure (includes local anaesthetic administration and toenail surgery). The second timepoint will be asked 1.25 hours following the procedure 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
1.25 hours following the procedure 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 Alcohol consumption in the 24 hours prior to the procedure
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.

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)
Simple randomisation using a randomisation table created by computer software
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
A sample size calculation has been performed based on a mean difference of three increments on the VNPRS (justified on the basis that methoxyflurane is likely to be more effective in this study than for trauma where a difference of 1.5 was found (Coffey et al., 2014)), and a standard deviation of 3/10 (Cohen et al., 2022), results in a sample size of 40 participants required in total (20 in each arm) accounting for drop-out of no more than 10%.

• The two groups will be compared statistically at baseline using the Fisher’s exact test. The Wilcoxon rank-sum test will be used for non-normally distributed continuous variables and the independent student’s t-test will be used for normally distributed continuous variables.
• The distribution of the primary outcome measure VNPRS (as reported in the survey one hour post procedure) will be assessed using visual inspection of plotted data and a Shapiro-Wilk test for normality. If an assumption of normally distributed pain scores is reasonable based on our observed data, then an independent student’s t-test will be used to compare the two groups. If the assumption of normality isn’t met, simple transformations will be used to achieve normality, proceeding as above if normality is achieved. If despite these transformations, normality of distribution cannot be assumed, then the pain scores will be categorised into no/mild pain (0-3), moderate pain (4-7), and severe pain (8-10), and we will utilise ordinal (if a proportional hazard assumption is valid) or multinomial regression (if the proportional hazard assumption is invalid) analysis.
• Secondary outcomes of anxiety reduction and user satisfaction will be compared between the two groups as described below.
• VNARS will be compared across the two time points (baseline versus immediately following procedure) using a t-test or Kruskall Wallis rank-sum test.
• Ordinal or multinomial regression will be used to assess differences in the proportion of patients who report being ‘very’ or ‘extremely’ satisfied with the procedure experience between groups. Convenience ratings will be assessed the same way.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/09/2023
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
40
Accrual to date
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
Submitted, not yet approved
Ethics committee name [1] 313520 0
Southern Adelaide Clinical Human Research Ethics Committee
Ethics committee address [1] 313520 0
Flinders Medical Centre
Flinders Drive, Bedford Park SA 5042
Ethics committee country [1] 313520 0
Australia
Date submitted for ethics approval [1] 313520 0
19/05/2023
Approval date [1] 313520 0
Ethics approval number [1] 313520 0
Ethics committee name [2] 313552 0
UniSA Human Research Ethics Committee
Ethics committee address [2] 313552 0
City East University of South Australia GPO Box 2471. Adelaide SA 5001
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
Ingrown toenails are a common presentation to any podiatry setting (Borges et al., 2017; Khunger & Kandhari, 2012). Although the true prevalence of this condition is difficult to determine, it has been reported to occur in approximately 2.5-5% of the population (Vural et al., 2018). Treatment often involves surgical excision using a local anaesthetic digital ring block (most commonly using plain lidocaine) (Eekhof et al., 2012). These injections can be a source of pain and anxiety for patients. If patients have a severe needle phobia, they are often referred to have the procedure conducted in theatre under a general anaesthetic. Hundreds of South Australians are currently on the public elective surgery waiting list for this procedure, the majority of which are triaged as a Category 3 with a recommended waiting time of within 365 days (Australian Institute of Health and Welfare, 2023). These patients risk prolonged infection, pain, and deterioration of their condition, which can place unnecessary emotional and economic burden on the patient, and the health care system (Oudhoff et al., 2007).

SA Health, as the provider of public health in South Australia, have recently approved the use of inhaled methoxyflurane by Podiatrists who meet prescribing requirements. The use of methoxyflurane for podiatric surgical procedures can provide a lower risk and more timely alternative for patients with a needle phobia to receive care without the need for general anaesthesia (Jephcott et al., 2018). In this situation, methoxyflurane can be used as an analgesic prior to and during the local anaesthetic injections enabling many more patients to have their procedure performed in outpatient (OPD) clinics. In addition to improving patient outcomes, this could reduce elective surgical waiting lists and the demand for surgical services, reducing the overall cost that these procedures would otherwise have on the health care system.

Hypothesis: Is self-administered, inhaled methoxyflurane (Penthrox®) effective in reducing pain during local anaesthetic administration in a Podiatry Outpatient setting?
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
claire.huxtable@sa.gov.au
Contact person for public queries
Name 128427 0
Ms 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
claire.huxtable@sa.gov.au
Contact person for scientific queries
Name 128428 0
Ms 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
claire.huxtable@sa.gov.au

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.