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Trial registered on ANZCTR


Registration number
ACTRN12615001105538
Ethics application status
Approved
Date submitted
11/08/2015
Date registered
21/10/2015
Date last updated
19/11/2020
Date data sharing statement initially provided
16/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A clinical research study that is testing whether Penthrox (methoxyflurane) plus local anaesthetic reduces pain and discomfort for men having their first transrectal ultrasound-guided prostate biopsy compared to local anaesthetic alone
Scientific title
A phase 3 double-blind placebo-controlled randomized trial of methoxyflurane with periprostatic local anaesthesia to reduce the discomfort of transrectal ultrasound-guided prostate biopsy (Pain-Free TRUS B)
Secondary ID [1] 287151 0
ANZUP 1501
Universal Trial Number (UTN)
U1111-1172-4458
Trial acronym
Pain-Free TRUS B
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Biopsy of the prostate for a raised PSA or an abnormal digital rectal examination. 295711 0
Condition category
Condition code
Cancer 295991 295991 0 0
Prostate
Anaesthesiology 296209 296209 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Inhaled methoxyflurane, provided as a commercial pack of one Penthrox (Registered Trademark) Inhaler, containing 3mL methoxyflurane, of which participants choose how many puffs they feel they need.
Administration will commence approximately one minute before insertion of the rectal probe.
To use the inhaler, the patient will put their lips around the mouthpiece and take normal sized breaths as required. Participants may choose to inhale throughout the entire procedure, however will only receive one pack, and therefore a maximum of 3mL methoxyflurane.
All participants will subsequently receive standard therapy (PILA) as standard of care. PILA consists of periprostatic injections of approximately 2.5mL of 2% lignocaine into each of the two sides of the base of the prostate gland at the junction of the seminal vesicle, using a 23g needle, administered about 5 minutes before doing the first biopsy.
The Pharmacy Department will maintain a record of drugs dispensed for each participant as well as a record of drug receipt and drug destruction as appropriate.

Intervention code [1] 292422 0
Treatment: Drugs
Comparator / control treatment
Placebo (inhaled 0.9% saline), provided as one Penthrox registered trademark Inhaler containing 3mL 0.9% saline, of which participants choose how many puffs they feel they need.
Control group
Placebo

Outcomes
Primary outcome [1] 295662 0
Pain rated by participants will be self-rated using a numeric rating scale with verbal anchors from 0 (no trouble at all) to 10 (worst I can imagine).
Timepoint [1] 295662 0
Pain will be assessed twice: at about 15 minutes after and 7 - 35 days after the TRUS biopsy
Secondary outcome [1] 316144 0
Composite Secondary Outcome: Other aspects of the biopsy experience rated by participants including how troubled they were by: discomfort, feeling embarrassed, the sounds, fear of the biopsy, fear of the results, drowsiness, feeling dizzy or light-headed, nausea, vomiting, and the whole experience. Participants will also rate ‘How much better or worse than expected’ were the pain, the discomfort, and the whole experience, again rated on 10 point scale from 0 (much better) to 5 (as expected) to 10 (much worse).
Timepoint [1] 316144 0
Rated at 15 minutes and 7-35 days after the biopsy
Secondary outcome [2] 316145 0
Willingness to undergo a biopsy in the future assessed by a questionnaire designed specifically for this study.
Timepoint [2] 316145 0
Rated at 15 minutes and 7-35 days after the biopsy
Secondary outcome [3] 316146 0
Urologist's ratings of the participant's biopsy experience, assessed by a questionnaire designed specifically for this study
Timepoint [3] 316146 0
On the same day as the TRUS biopsy
Secondary outcome [4] 316147 0
Biopsy completion is defined as performance of 80% or more of the planned number of biopsies. The number of planned biopsies is recorded by the urologist before the TRUS Biopsy. The number of biopsies performed is recorded by the urologist after the TRUS biopsy.
Timepoint [4] 316147 0
Defined as performance of 80% or more of the planned number of biopsies after the TRUS biopsy, after completion of all study participant biopsy procedures.
Secondary outcome [5] 316151 0
Frequency of specified adverse events. Surgical adverse events of interest (complications) include nausea, vomiting, dizziness, vasovagal episodes, fever, infection, urinary retention, or death within 30 days of the TRUS biopsy. the Clavien-Dindo Classification will be used to grade the most severe complication and SUSARS will be coded using the NCI CTCAEv4.03.
Timepoint [5] 316151 0
Adverse events will be recorded after the TRUS biopsy (before the participant leaves the clinic), and 7-35 days after the biopsy.
Secondary outcome [6] 316152 0
Frequency of hospitalisation by reviewing hospital records.
Timepoint [6] 316152 0
Details will be recorded for each emergency department visit and each non-elective hospital admission that occurs within 30 days of the TRUS biopsy.

Eligibility
Key inclusion criteria
1. Males older than 18 years scheduled to undergo a TRUS biopsy of the prostate.
2. No history of significant liver disease
3. No history of significant renal disease
4. Willing and able to complete questionnaires in English
5. Willing and able to undergo TRUS biopsy within 7 days of randomisation
6. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments
7. Signed, written informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. Previous TRUS biopsy of the prostate
2. Personal or family history of malignant hyperthermia
3. Hypersensitivity to fluorinated anaesthetics or other inhalational anaesthetics
4. Concurrent use of barbiturates or tetracycline antibiotics
5. Concurrent illness that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety
6. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse.

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)
Participants must meet all of the eligibility criteria.
Randomisation will be carried out by site staff via an internet based central randomisation system.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be in a 1:1 ratio and stratified by the following characteristics:
1) Age (18-60 years versus older than 60)
2) Study site
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The primary analysis will be a comparison between treatment groups on the pain score (following biopsy) using an analysis of variance with centre fitted as a covariate. Additional covariates will be added as part of a secondary analysis to explore the potential of baseline characteristics as prognostic factors or effect modifiers. Comparisons between treatment groups on other continuous secondary endpoints will be undertaken using a comparable approach to that used on the primary endpoint. Binary (and ordinal) secondary endpoints (e.g. treatment completion) will be undertaken using (ordinal) logistic regression with centre fitted as a covariate. A descriptive analysis of the safety data will be undertaken.
420 participants provides over 85% power at the two-sided 5% level of significance to detect a 0.80 point difference in mean pain scores (on scale from 0-10) assuming a standard deviation of 2.5 whilst allowing for missing data. A 0.80 point shift in mean pain scores should correspond to a reduction of more than 1/3 in the proportion of men reporting troublesome levels of pain.


Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
30/11/2015
Actual
13/01/2016
Date of last participant enrolment
Anticipated
30/06/2020
Actual
4/11/2019
Date of last data collection
Anticipated
Actual
31/03/2020
Sample size
Target
420
Accrual to date
Final
420
Recruitment in Australia
Recruitment state(s)
NSW,WA,VIC
Recruitment hospital [1] 4099 0
The Alfred - Prahran
Recruitment hospital [2] 4100 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [3] 4101 0
Westmead Hospital - Westmead
Recruitment hospital [4] 4102 0
Casey Hospital - Berwick
Recruitment postcode(s) [1] 10028 0
3181 - Prahran
Recruitment postcode(s) [2] 10029 0
6150 - Murdoch
Recruitment postcode(s) [3] 10030 0
2145 - Westmead
Recruitment postcode(s) [4] 10031 0
3806 - Berwick
Recruitment outside Australia
Country [1] 7053 0
New Zealand
State/province [1] 7053 0
North and South Islands

Funding & Sponsors
Funding source category [1] 291721 0
Government body
Name [1] 291721 0
Cancer Australia
Country [1] 291721 0
Australia
Funding source category [2] 291814 0
Charities/Societies/Foundations
Name [2] 291814 0
Prostate Cancer Foundation of Australia
Country [2] 291814 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
Level 6
Jane Foss Russell Building GO2
University of Sydney NSW 2006
Country
Australia
Secondary sponsor category [1] 290394 0
Other Collaborative groups
Name [1] 290394 0
Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group
Address [1] 290394 0
Lifehouse, Level 6
119-143 Missenden Road
Camperdown NSW 2050
Country [1] 290394 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293243 0
SLHD Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 293243 0
c/- Research Development Office
Royal Prince Alfred Hospital
Missenden Road
CAMPERDOWN NSW 2050
Ethics committee country [1] 293243 0
Australia
Date submitted for ethics approval [1] 293243 0
05/06/2015
Approval date [1] 293243 0
31/08/2015
Ethics approval number [1] 293243 0
X15-0217 & HREC/15/RPAH/286

Summary
Brief summary
The purpose of this study is to see if the discomfort of a prostate biopsy can be reduced by a drug called methoxyflurane (Penthrox) given with a simple inhaler, popularly known as the ‘green whistle’, and widely used by ambulance officers and first aid services. Methoxyflurane is already approved in Australia for the relief of pain in patients having surgical procedures.
Who is it for?
You may be eligible to participate in this study if you are a male, aged 18 or over, who has been scheduled for your first transrectal ultrasound-guided prostate biopsy.
Study Details
All participants have injections of a local anaesthetic (lignocaine) around their prostate before the biopsy. This is the standard way of reducing the discomfort of a prostate biopsy. Before having the local anaesthetic, all participants are given the study treatment which is a ‘green whistle’ inhaler after being shown how to use it. After their biopsy, participants fill out short, simple forms to let us know how they felt. In this study, one half of the participants are given inhalers loaded with methoxyflurane (the active inhaler group). The other half are given inhalers that look and smell the same, but are loaded with saline solution alone (the placebo inhaler group).
Comparing the results in these two groups at the end of the study will show how good methoxyflurane is at reducing the discomfort of a prostate biopsy. It is hoped that this study will improve understanding of drugs which may be used to reduce discomfort of prostate biopsies for future patients.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 59038 0
Mr Nick Buchan
Address 59038 0
Canterbury Urology Research Trust 132 Peterborough Street, Christchurch, 8013
Country 59038 0
New Zealand
Phone 59038 0
+61 2 9562 5000
Fax 59038 0
+61 2 9562 5094
Email 59038 0
[email protected]
Contact person for public queries
Name 59039 0
TRUS B Trial Coordinator
Address 59039 0
NHMRC CTC
Locked Bag 77
Camperdown NSW 1450
Country 59039 0
Australia
Phone 59039 0
+61 2 9562 5000
Fax 59039 0
+61 2 9562 5094
Email 59039 0
[email protected]
Contact person for scientific queries
Name 59040 0
TRUS B Trial Coordinator
Address 59040 0
NHMRC CTC
Locked Bag 77
Camperdown NSW 1450
Country 59040 0
Australia
Phone 59040 0
+61 2 9562 5000
Fax 59040 0
+61 2 9562 5094
Email 59040 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
Please contact CTC for data sharing policy


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.