Anorectal Application of 5% Lidocaine Cream Reduces Pain Prior to Periprostatic Nerve Block During Transrectal Ultrasound Guided Biopsy

Anorectal Application of 5% Lidocaine Cream Reduces Pain Prior to Periprostatic Nerve Block During Transrectal Ultrasound Guided Biopsy: Randomized, Prospective Controlled Study

Transrectal ultrasound guided prostate biopsy is performed with a periprostatic nerve block to the neurovascular bundle bilaterally. This does not reduce the pain due to probe insertion and manipulation prior to nerve blockage.

Our study goal is to assess whether topical analgesia would reduce pain during the early stages of the procedure.

Study Overview

• Status: Completed
• Conditions: Pain; Prostate Cancer; Rectal/Anal
• Intervention / Treatment: Procedure: Trans rectal ultrasound guided prostate biopsy; Procedure: Trans rectal ultrasound; Procedure: Prostate biopsy; Procedure: Periprostatic nerve block

Detailed Description

Prospective, randomized controlled study. Patients signed an informed consent form. Exclusion criteria were Lidocaine allergy or pre-planned general anesthesia.

Patients were randomized into 6 groups: (1) nerve block with 5 ml 1% lidocaine for each neurovascular bundle + perianal topical application of 10 ml 5% lidocaine cream; (2) as in (1) plus application of 10 ml 5% lidocaine cream evenly on rectal walls. For each approach exposure times of 5, 10 and 20 minutes were allowed, all together 6 groups plus a control group of patients who received periprostatic nerve block only. A 0-10 Visual analogue scale (VAS) was filled by the patients at 5 time points: immediately after probe insertion, during probe manipulation and prostate assessment, immediately following neurovascular bundle nerve blockage, after prostate biopsies and a global pain estimation of the procedure.

• Study Type: Interventional
• Enrollment (Actual): 284
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Males referred to TRUSGBx due to elevated prostate specific antigen (PSA)
• Abnormal findings on digital rectal examination (DRE)
• Repeat biopsies as part of Active Surveillance (AS)
• Continuously elevated PSA levels despite prior negative for malignancy biopsies
• Previous histological findings of significant HGPIN were enrolled

Exclusion Criteria:

• Known sensitivity to Lidocaine
• Pre-planned biopsy under general anesthesia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Single

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: External Anal application - 5 minutes exposure; Anal application of lidocaine cream 5% for 5 minutes before probe insertion. After probe insertion and prior to biopsy, a periprostatic nerve block was performed with 10 mL of 1% Lidocaine (5 mL on each side).	Procedure: Trans rectal ultrasound guided prostate biopsy; The investigators checked visual analogue scale of pain at different time periods: prior to probe insertion, during probe insertion. during probe manipulation in the rectum, during performance of periprostatic nerve block, during actual biopsy collection and at termination of procedure.; Procedure: Trans rectal ultrasound; Performing a prostate biopsy using a transrectal ultrasound probe - the BK pro focus 2202 transrectal ultrasound and the 8808 bi-plane transrectal probe; Other Names: BK pro focus 2202 transrectal ultrasound and the 8808 bi-plane transrectal probe; Procedure: Prostate biopsy; Prostate biopsy guided by a transrectal ultrasound with an 18 gauge needle; Procedure: Periprostatic nerve block; Performing a bilateral peri-prostatic nerve block with 10 mL of 1% lidocaine (5 mL on each side)
Active Comparator: External Anal application - 10 minutes exposure; Anal application of lidocaine cream 5% for 10 minutes before probe insertion. After probe insertion and prior to biopsy, a periprostatic nerve block was performed with 10 mL of 1% Lidocaine (5 mL on each side).	Procedure: Trans rectal ultrasound guided prostate biopsy; The investigators checked visual analogue scale of pain at different time periods: prior to probe insertion, during probe insertion. during probe manipulation in the rectum, during performance of periprostatic nerve block, during actual biopsy collection and at termination of procedure.; Procedure: Trans rectal ultrasound; Performing a prostate biopsy using a transrectal ultrasound probe - the BK pro focus 2202 transrectal ultrasound and the 8808 bi-plane transrectal probe; Other Names: BK pro focus 2202 transrectal ultrasound and the 8808 bi-plane transrectal probe; Procedure: Prostate biopsy; Prostate biopsy guided by a transrectal ultrasound with an 18 gauge needle; Procedure: Periprostatic nerve block; Performing a bilateral peri-prostatic nerve block with 10 mL of 1% lidocaine (5 mL on each side)
Active Comparator: External Anal application - 20 minutes exposure; Anal application of lidocaine cream 5% for 20 minutes before probe insertion. After probe insertion and prior to biopsy, a periprostatic nerve block was performed with 10 mL of 1% Lidocaine (5 mL on each side).	Procedure: Trans rectal ultrasound guided prostate biopsy; The investigators checked visual analogue scale of pain at different time periods: prior to probe insertion, during probe insertion. during probe manipulation in the rectum, during performance of periprostatic nerve block, during actual biopsy collection and at termination of procedure.; Procedure: Trans rectal ultrasound; Performing a prostate biopsy using a transrectal ultrasound probe - the BK pro focus 2202 transrectal ultrasound and the 8808 bi-plane transrectal probe; Other Names: BK pro focus 2202 transrectal ultrasound and the 8808 bi-plane transrectal probe; Procedure: Prostate biopsy; Prostate biopsy guided by a transrectal ultrasound with an 18 gauge needle; Procedure: Periprostatic nerve block; Performing a bilateral peri-prostatic nerve block with 10 mL of 1% lidocaine (5 mL on each side)
Active Comparator: External Anal plus intrarectal - 5 minutes exposure; Anal application plus intrarectal application of 5% lidocaine cream for 5 minutes before probe insertion. After probe insertion and prior to biopsy, a periprostatic nerve block was performed with 10 mL of 1% Lidocaine (5 mL on each side).	Procedure: Trans rectal ultrasound guided prostate biopsy; The investigators checked visual analogue scale of pain at different time periods: prior to probe insertion, during probe insertion. during probe manipulation in the rectum, during performance of periprostatic nerve block, during actual biopsy collection and at termination of procedure.; Procedure: Trans rectal ultrasound; Performing a prostate biopsy using a transrectal ultrasound probe - the BK pro focus 2202 transrectal ultrasound and the 8808 bi-plane transrectal probe; Other Names: BK pro focus 2202 transrectal ultrasound and the 8808 bi-plane transrectal probe; Procedure: Prostate biopsy; Prostate biopsy guided by a transrectal ultrasound with an 18 gauge needle; Procedure: Periprostatic nerve block; Performing a bilateral peri-prostatic nerve block with 10 mL of 1% lidocaine (5 mL on each side)
Active Comparator: External Anal plus intrarectal - 10 minutes exposure; Anal application plus intrarectal application of 5% lidocaine cream for 10 minutes before probe insertion. After probe insertion and prior to biopsy, a periprostatic nerve block was performed with 10 mL of 1% Lidocaine (5 mL on each side).	Procedure: Trans rectal ultrasound guided prostate biopsy; The investigators checked visual analogue scale of pain at different time periods: prior to probe insertion, during probe insertion. during probe manipulation in the rectum, during performance of periprostatic nerve block, during actual biopsy collection and at termination of procedure.; Procedure: Trans rectal ultrasound; Performing a prostate biopsy using a transrectal ultrasound probe - the BK pro focus 2202 transrectal ultrasound and the 8808 bi-plane transrectal probe; Other Names: BK pro focus 2202 transrectal ultrasound and the 8808 bi-plane transrectal probe; Procedure: Prostate biopsy; Prostate biopsy guided by a transrectal ultrasound with an 18 gauge needle; Procedure: Periprostatic nerve block; Performing a bilateral peri-prostatic nerve block with 10 mL of 1% lidocaine (5 mL on each side)
Active Comparator: External Anal plus intrarectal - 20 minutes exposure; Anal application plus intrarectal application of 5% lidocaine cream for 20 minutes before probe insertion. After probe insertion and prior to biopsy, a periprostatic nerve block was performed with 10 mL of 1% Lidocaine (5 mL on each side).	Procedure: Trans rectal ultrasound guided prostate biopsy; The investigators checked visual analogue scale of pain at different time periods: prior to probe insertion, during probe insertion. during probe manipulation in the rectum, during performance of periprostatic nerve block, during actual biopsy collection and at termination of procedure.; Procedure: Trans rectal ultrasound; Performing a prostate biopsy using a transrectal ultrasound probe - the BK pro focus 2202 transrectal ultrasound and the 8808 bi-plane transrectal probe; Other Names: BK pro focus 2202 transrectal ultrasound and the 8808 bi-plane transrectal probe; Procedure: Prostate biopsy; Prostate biopsy guided by a transrectal ultrasound with an 18 gauge needle; Procedure: Periprostatic nerve block; Performing a bilateral peri-prostatic nerve block with 10 mL of 1% lidocaine (5 mL on each side)
Sham Comparator: Control group; No anal application of lidocaine cream prior to probe insertion. After probe insertion and prior to biopsy, a periprostatic nerve block was performed with 10 mL of 1% Lidocaine (5 mL on each side).	Procedure: Trans rectal ultrasound guided prostate biopsy; The investigators checked visual analogue scale of pain at different time periods: prior to probe insertion, during probe insertion. during probe manipulation in the rectum, during performance of periprostatic nerve block, during actual biopsy collection and at termination of procedure.; Procedure: Trans rectal ultrasound; Performing a prostate biopsy using a transrectal ultrasound probe - the BK pro focus 2202 transrectal ultrasound and the 8808 bi-plane transrectal probe; Other Names: BK pro focus 2202 transrectal ultrasound and the 8808 bi-plane transrectal probe; Procedure: Prostate biopsy; Prostate biopsy guided by a transrectal ultrasound with an 18 gauge needle; Procedure: Periprostatic nerve block; Performing a bilateral peri-prostatic nerve block with 10 mL of 1% lidocaine (5 mL on each side)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain level before probe insertion	Self reported by the patient using a 0-10 visual analogue scale. 0 being no pain at all, 10 being worst pain imaginable.	Before transrectal ultrasound probe insertion
Pain level at TRUS probe insertion	Self reported by the patient using a 0-10 visual analogue scale. 0 being no pain at all, 10 being worst pain imaginable.	During transrectal ultrasound probe insertion into the rectum (defined as beginning of procedure)
Pain level during TRUS probe manipulation in the rectum	Self reported by the patient using a 0-10 visual analogue scale. 0 being no pain at all, 10 being worst pain imaginable.	During transrectal ultrasound probe manipulation in the rectum (estimated at 0-2 minutes length)
Pain level during periprostatic nerve block	Self reported by the patient using a 0-10 visual analogue scale. 0 being no pain at all, 10 being worst pain imaginable.	During periprostatic nerve block (rectal wall puncture with needle, estimated at 2-3 minutes after beginning of procedure)
Pain level during biopsy collection	Self reported by the patient using a 0-10 visual analogue scale. 0 being no pain at all, 10 being worst pain imaginable.	During biopsy collection using an 18-gauge needle (estimated at 3-10 minutes from beginning of procedure)
Pain level at termination of procedure	Self reported by the patient using a 0-10 visual analogue scale. 0 being no pain at all, 10 being worst pain imaginable.	At termination of procedure (total estimated length of procedure is 10 minutes).

Collaborators and Investigators

• Sponsor: Assaf-Harofeh Medical Center
• Investigators: Study Chair: Judith Ben Zvi, Assaf Harofeh Medical Center ethical committee for experiments in humans

Publications and helpful links

General Publications

• Lee C, Woo HH. Current methods of analgesia for transrectal ultrasonography (TRUS)-guided prostate biopsy -- a systematic review. BJU Int. 2014 Mar;113 Suppl 2:48-56. doi: 10.1111/bju.12433.
• Tiong HY, Liew LC, Samuel M, Consigliere D, Esuvaranathan K. A meta-analysis of local anesthesia for transrectal ultrasound-guided biopsy of the prostate. Prostate Cancer Prostatic Dis. 2007;10(2):127-36. doi: 10.1038/sj.pcan.4500935. Epub 2007 Jan 9.
• Wang J, Wang L, Du Y, He D, Chen X, Li L, Nan X, Fan J. Addition of intrarectal local analgesia to periprostatic nerve block improves pain control for transrectal ultrasonography-guided prostate biopsy: a systematic review and meta-analysis. Int J Urol. 2015 Jan;22(1):62-8. doi: 10.1111/iju.12595. Epub 2014 Aug 21.
• Raber M, Scattoni V, Roscigno M, Deho F, Briganti A, Salonia A, Gallina A, Di Girolamo V, Montorsi F, Rigatti P. Topical prilocaine-lidocaine cream combined with peripheral nerve block improves pain control in prostatic biopsy: results from a prospective randomized trial. Eur Urol. 2008 May;53(5):967-73. doi: 10.1016/j.eururo.2007.09.005. Epub 2007 Sep 18.
• Giannarini G, Autorino R, Valent F, Mogorovich A, Manassero F, De Maria M, Morelli G, Barbone F, Di Lorenzo G, Selli C. Combination of perianal-intrarectal lidocaine-prilocaine cream and periprostatic nerve block for pain control during transrectal ultrasound guided prostate biopsy: a randomized, controlled trial. J Urol. 2009 Feb;181(2):585-91; discussion 591-3. doi: 10.1016/j.juro.2008.10.002. Epub 2008 Dec 13.
• Barcohana N, Duperon DF, Yashar M. The relationship of application time to EMLA efficacy. J Dent Child (Chic). 2003 Jan-Apr;70(1):51-4.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): July 1, 2017

Study Registration Dates

• First Submitted: January 20, 2019
• First Submitted That Met QC Criteria: August 19, 2019
• First Posted (Actual): August 21, 2019

Study Record Updates

• Last Update Posted (Actual): January 13, 2020
• Last Update Submitted That Met QC Criteria: January 8, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: Assaf-HarofehMC 0289-15-ASF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No