Trial of Methoxyflurane With Periprostatic Local Anaesthesia to Reduce the Discomfort of TRUS B (TRUSB)

• ClinicalTrials.gov Identifier: NCT02604225
• Recruitment Status: Completed
• First Posted: November 13, 2015
• Last Update Posted: May 11, 2020
• Sponsor: University of Sydney
• Collaborator: Australian and New Zealand Urogenital and Prostate Cancer Trials Group
• Information provided by (Responsible Party): University of Sydney

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Cancer	Drug: Methoxyflurane; Drug: Placebo	Phase 3

Detailed Description:

Background Transrectal ultrasound-guided (TRUS) prostate biopsy is associated with significant discomfort, despite the use of periprostatic infiltration of local anaesthetic (PILA).

General aim To determine the efficacy and safety of inhaled methoxyflurane plus PILA versus PILA alone in men undergoing TRUS biopsy of the prostate.

Objectives (endpoints)

To determine the effects of inhaled methoxyflurane on:

Primary

1. Pain-rated by participants 15 minutes after biopsy.

   Secondary

2. Other aspects of the biopsy experience rated by participants 15 minutes and 7-35 days after the biopsy
3. Willingness to undergo a biopsy in the future
4. Urologist's ratings of the participant's biopsy experience (study specific questionnaire completed after the biopsy)
5. Biopsy completion (80% or more of the planned number of biopsies being taken)
6. Frequency of specified adverse events (CTC AE v4.03 and Clavien-Dindo Classification).
7. Frequency of hospitalisation

Design Multi-centre, placebo-controlled, double-blinded, centrally randomised (1:1), stratified, phase 3 trial.

Target population Men scheduled to undergo their first TRUS biopsy of the prostate for a raised PSA or abnormal digital rectal examination (DRE).

Study treatments

Participants randomised to inhaled:

Methoxyflurane (Penthrox®, experimental group). OR Placebo (0.9% saline, control group

All participants are subsequently treated with PILA (2% lignocaine), injected into and around the prostate about 5 minutes before the biopsy.

Assessments Participants will be assessed at time of scheduling of the TRUS prostate biopsy (up to 84 days prior to randomisation), on the day of biopsy, and at the post biopsy clinic (7-35 days after the biopsy). Assessments comprise of medical history and standard blood tests at baseline, patient questionnaire on the day of biopsy and post(7-35 days) biopsy and safety assessments on the day of biopsy and post (7--35 days) biopsy.

Statistical considerations 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 420 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official 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
• Study Start Date: December 2015
• Actual Primary Completion Date: December 5, 2019
• Actual Study Completion Date: December 30, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Penthrox; Methoxyflurane	Drug: Methoxyflurane; Participants randomised to the experimental arm will inhale methoxyflurane administered through the Penthrox® inhaler starting approximately one minute before insertion of the rectal probe.; Other Name: Penthrox®
Placebo Comparator: Placebo; Saline 0.9%	Drug: Placebo; Participants randomised to the control arm will inhale 0.9% saline administered through the Penthrox® inhaler starting approximately one minute before insertion of the rectal probe.; Other Name: Saline 0.9%

Outcome Measures

Primary Outcome Measures :

1. 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). [ Time Frame: Pain will be assessed at 15 minutes after the TRUS biopsy ]

Secondary Outcome Measures :

1. Other aspects of the biopsy experience rated by participants on the Patient's Experience of TRUS biopsy questionnaire. [ Time Frame: Rated at 15 minutes after the biopsy ]
2. Other aspects of the biopsy experience rated by participants on the Patient's Experience of TRUS biopsy questionnaire. [ Time Frame: Rated at 7-35 days after the biopsy ]
3. Willingness to undergo a biopsy in the future assessed by a questionnaire designed specifically for this study. [ Time Frame: Rated at 15 minutes and 7-35 days after the biopsy ]
4. Urologist's ratings of the participant's biopsy experience, assessed by a questionnaire [ Time Frame: On the same day as the TRUS biopsy ]
5. Biopsy completion rate. [ Time Frame: Recorded on day of TRUS biopsy. ]
6. Frequency of specified adverse events. [ Time Frame: Adverse events will be recorded after the TRUS biopsy (before the participant leaves the clinic), and 7-35 days after the biopsy. ]
7. Frequency of hospitalisation by reviewing hospital records. [ Time Frame: 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 Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Males older than 18 years scheduled to undergo a TRUS biopsy of the prostate.
2. Adequate liver function: ALT, AST, or bilirubin ≤ 2 x ULN
3. Adequate renal function: serum eGFR> 30 ml/min/1.73m2
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

Exclusion Criteria:

1. Previous TRUS biopsy of the prostate
2. Personal or family history of malignant hyperthermia
3. History of significant liver disease
4. Hypersensitivity to fluorinated anaesthetics or other inhalational anaesthetics
5. Concurrent use of barbiturates or tetracycline antibiotics
6. Concurrent illness that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety
7. 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.

Contacts and Locations

Locations

Australia, New South Wales

Concord Hospital

Concord, New South Wales, Australia, 2640

Australian Clinical Trials

Wahroonga, New South Wales, Australia, 2640

Australia, Victoria

Casey Hospital

Berwick, Victoria, Australia

The Alfred Hospital

Prahran, Victoria, Australia

Australia, Western Australia

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

Australia

Westmead Hospital

Westmead, Australia

New Zealand

Canterbury Urology Research Trust

Christchurch, New Zealand

Sponsors and Collaborators

University of Sydney

Australian and New Zealand Urogenital and Prostate Cancer Trials Group

Investigators

• Study Chair: Jeremy Grummet; Principal Investigator

More Information

• Responsible Party: University of Sydney
• ClinicalTrials.gov Identifier: NCT02604225
• Other Study ID Numbers: ANZUP 1501; ACTRN12615001105538 ( Registry Identifier: ANZCTR )
• First Posted: November 13, 2015
• Last Update Posted: May 11, 2020
• Last Verified: May 2020

Keywords provided by University of Sydney:

Anaethesiology

Additional relevant MeSH terms:

Methoxyflurane; Anesthetics, Inhalation; Anesthetics, General; Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs