The Effect of Local Anesthetic Solution in the Bladder Prior to Botox Injections in the Bladder

NCT05415865 | Unknown Phase 3 DMC

• 1 other identifier: BTXA2021
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate the effect of Lidocaine solution versus placebo (isotonic Sodium Chloride NaCl) disposed inside the urinary bladder as intravesical anesthesia prior to onabotulinum toxin A injections in the treatment of urgency urinary incontinence.

Conditions

Urge Incontinence; Overactive Bladder; Anesthesia, Local; Pain, Procedural; Urinary Tract Infections; Hematuria

Keywords

Urge incontinence; Anesthesia, Local; Botulinum Toxins, Type A; Overactive Bladder; Alkalinized Lidocaine; Double-blind Method; Visual Analog Scale; Administration, Intravesical

Outcome Measures

Primary Outcomes (1)

• 100 mm Visual Analogue Scale (VAS) score

  The maximum pain score reported by using VAS

  The participant is handed the VAS in paper form and asked to grade the intensity of pain according to the VAS by making a handwritten mark on the VAS immediately after the BTX-A injections

Secondary Outcomes (4)

• Post-void residual requiring Clean Intermittent Catheterization (CIC)

  Phone consultation one week after each treatment

• Urinary tract infection (UTI)

  Phone consultation one week after each treatment

• Hematuria

  Phone consultation one week after each treatment

• 5-point rating scale

  Phone consultation one week after each treatment

Study Arms (2)

Alkalinized Lidocaine, then Placebo

ACTIVE COMPARATOR

Participants will have Lidocaine Hydrochloride 20 mg/ml, 20 ml and Sodium hydrogen carbonate 1 mmol/ml, 10 ml (ie a total of 30 ml) installed in the bladder for 15 minutes prior to the BTXA-injection procedure. When signing up for the next BTXA-injection with a wash out period of minimum three months, participants will have the matching placebo containing Sodium Chloride 9 g/L, 20 ml and Sodium Chloride 9 g/L, 10 ml, a total of 30 ml installed in the bladder for 15 minutes prior to the BTXA-injection procedure.

Combination Product: Alkalinized Lidocaine; Drug: Placebo Sodium Chloride 0.9% Inj

Placebo, then Alkalinized Lidocaine

ACTIVE COMPARATOR

Participants will have placebo containing Sodium Chloride 9 g/L, 20 ml and Sodium Chloride 9 g/L, 10 ml, a total of 30 ml installed in the bladder 15 minutes prior to the BTXA-injection procedure. When signing up for the next BTXA-injection with a wash out period of minimum three months, participants will have Lidocaine Hydrochloride 20 mg/ml, 20 ml and Sodium hydrogen carbonate 1 mmol/ml, 10 ml (ie a total of 30 ml) installed in the bladder for 15 minutes prior to the BTXA-injection procedure.

Combination Product: Alkalinized Lidocaine; Drug: Placebo Sodium Chloride 0.9% Inj

Interventions

Alkalinized Lidocaine COMBINATION_PRODUCT

20 ml of Lidocaine Hydrochloride and 10 ml of Sodium hydrogen carbonate will be pulled up and mixed in a syringe on site, and 30 ml mixed solution in total will afterwards be installed in the bladder with a catheter.

Alkalinized Lidocaine, then Placebo; Placebo, then Alkalinized Lidocaine

Placebo Sodium Chloride 0.9% Inj DRUG

20 ml of Sodium Chloride 9 g/L and 10 ml of Sodium Chloride 9 g/L will be pulled up and mixed in a syringe on site, and 30 ml solution in total will afterwards be installed in the bladder with a catheter.

Alkalinized Lidocaine, then Placebo; Placebo, then Alkalinized Lidocaine

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female, age ≥18 years
• Admitted to treatment with BTX-A injections at the Urogynecological Clinic at Herlev Hospital due to UUI
• Able to read and understand Danish
• The female accepts to receive BTX-A injections as an outpatient treatment without the option of receiving sedative drugs

You may not qualify if:

• BTX-A allergy
• Neurological disorder that may affect bladder function (e.g. Multiple sclerosis or spinal cord inju-ry)
• Neurological disorder with neuromuscular transmission failure (i.e. Mystenia Gravis)
• Ongoing UTI or symptoms of UTI prior to treatment, assessed by principal investigator
• Any other bladder pathology at the time of cystoscopy if identified (includes trauma, stones, tu-mor)
• Pregnancy/breastfeeding women

Sponsors & Collaborators

• Herlev and Gentofte Hospital: lead
• Region Hovedstadens Apotek: collaborator

Study Sites (1)

Kvinde- og Bækkenbundssygdomme, klinik 1

Herlev, Capital Region, 2730, Denmark

RECRUITING

Related Publications (19)

• Haylen BT, de Ridder D, Freeman RM, Swift SE, Berghmans B, Lee J, Monga A, Petri E, Rizk DE, Sand PK, Schaer GN. An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Int Urogynecol J. 2010 Jan;21(1):5-26. doi: 10.1007/s00192-009-0976-9. Epub 2009 Nov 25.

  PMID: 19937315 BACKGROUND

• Vaughan CP, Johnson TM 2nd, Ala-Lipasti MA, Cartwright R, Tammela TL, Taari K, Auvinen A, Tikkinen KA. The prevalence of clinically meaningful overactive bladder: bother and quality of life results from the population-based FINNO study. Eur Urol. 2011 Apr;59(4):629-36. doi: 10.1016/j.eururo.2011.01.031. Epub 2011 Jan 25.

  PMID: 21306820 BACKGROUND

• Irwin DE, Milsom I, Kopp Z, Abrams P; EPIC Study Group. Symptom bother and health care-seeking behavior among individuals with overactive bladder. Eur Urol. 2008 May;53(5):1029-37. doi: 10.1016/j.eururo.2008.01.027. Epub 2008 Jan 16.

  PMID: 18243515 BACKGROUND

• Nitti VW, Ginsberg D, Sievert KD, Sussman D, Radomski S, Sand P, De Ridder D, Jenkins B, Magyar A, Chapple C; 191622-096 Investigators. Durable Efficacy and Safety of Long-Term OnabotulinumtoxinA Treatment in Patients with Overactive Bladder Syndrome: Final Results of a 3.5-Year Study. J Urol. 2016 Sep;196(3):791-800. doi: 10.1016/j.juro.2016.03.146. Epub 2016 Mar 30.

  PMID: 27038769 BACKGROUND

• Nambiar AK, Younis A, Khan ZA, Hildrup I, Emery SJ, Lucas MG. Alkalinized lidocaine versus lidocaine gel as local anesthesia prior to intra-vesical botulinum toxin (BoNTA) injections: A prospective, single center, randomized, double-blind, parallel group trial of efficacy and morbidity. Neurourol Urodyn. 2016 Apr;35(4):522-7. doi: 10.1002/nau.22750. Epub 2015 Mar 8.

  PMID: 25754188 BACKGROUND

• Nickel JC, Moldwin R, Lee S, Davis EL, Henry RA, Wyllie MG. Intravesical alkalinized lidocaine (PSD597) offers sustained relief from symptoms of interstitial cystitis and painful bladder syndrome. BJU Int. 2009 Apr;103(7):910-8. doi: 10.1111/j.1464-410X.2008.08162.x. Epub 2008 Nov 13.

  PMID: 19021619 BACKGROUND

• Henry R, Patterson L, Avery N, Tanzola R, Tod D, Hunter D, Nickel JC, Morales A. Absorption of alkalized intravesical lidocaine in normal and inflamed bladders: a simple method for improving bladder anesthesia. J Urol. 2001 Jun;165(6 Pt 1):1900-3. doi: 10.1097/00005392-200106000-00014.

  PMID: 11371877 BACKGROUND

• Narahashi T, Frazier T, Yamada M. The site of action and active form of local anesthetics. I. Theory and pH experiments with tertiary compounds. J Pharmacol Exp Ther. 1970 Jan;171(1):32-44. No abstract available.

  PMID: 5410936 BACKGROUND

• Henry RA, Patterson L, Nickel C, Morales A. Alkalinized intravesical lidocaine to treat interstitial cystitis: absorption kinetics in normal and interstitial cystitis bladders. Urology. 2001 Jun;57(6 Suppl 1):119. doi: 10.1016/s0090-4295(01)01069-x. No abstract available.

  PMID: 11378101 BACKGROUND

• Yanagi H, Sankawa H, Saito H, Iikura Y. Effect of lidocaine on histamine release and Ca2+ mobilization from mast cells and basophils. Acta Anaesthesiol Scand. 1996 Oct;40(9):1138-44. doi: 10.1111/j.1399-6576.1996.tb05577.x.

  PMID: 8933856 BACKGROUND

• Pereira E Silva R, Ponte C, Lopes F, Palma Dos Reis J. Alkalinized lidocaine solution as a first-line local anesthesia protocol for intradetrusor injection of onabotulinum toxin A: Results from a double-blinded randomized controlled trial. Neurourol Urodyn. 2020 Nov;39(8):2471-2479. doi: 10.1002/nau.24519. Epub 2020 Sep 21.

  PMID: 32956506 BACKGROUND

• Nitti VW, Dmochowski R, Herschorn S, Sand P, Thompson C, Nardo C, Yan X, Haag-Molkenteller C; EMBARK Study Group. OnabotulinumtoxinA for the treatment of patients with overactive bladder and urinary incontinence: results of a phase 3, randomized, placebo controlled trial. J Urol. 2013 Jun;189(6):2186-93. doi: 10.1016/j.juro.2012.12.022. Epub 2012 Dec 14.

  PMID: 23246476 BACKGROUND

• Duthie JB, Vincent M, Herbison GP, Wilson DI, Wilson D. Botulinum toxin injections for adults with overactive bladder syndrome. Cochrane Database Syst Rev. 2011 Dec 7;2011(12):CD005493. doi: 10.1002/14651858.CD005493.pub3.

  PMID: 22161392 BACKGROUND

• Dmochowski R, Chapple C, Nitti VW, Chancellor M, Everaert K, Thompson C, Daniell G, Zhou J, Haag-Molkenteller C. Efficacy and safety of onabotulinumtoxinA for idiopathic overactive bladder: a double-blind, placebo controlled, randomized, dose ranging trial. J Urol. 2010 Dec;184(6):2416-22. doi: 10.1016/j.juro.2010.08.021. Epub 2010 Oct 16.

  PMID: 20952013 BACKGROUND

• Cote TR, Mohan AK, Polder JA, Walton MK, Braun MM. Botulinum toxin type A injections: adverse events reported to the US Food and Drug Administration in therapeutic and cosmetic cases. J Am Acad Dermatol. 2005 Sep;53(3):407-15. doi: 10.1016/j.jaad.2005.06.011.

  PMID: 16112345 BACKGROUND

• Thrasher JB, Peterson NE, Donatucci CF. Lidocaine as a topical anesthetic for bladder biopsies. J Urol. 1991 Jun;145(6):1209-10. doi: 10.1016/s0022-5347(17)38577-4.

  PMID: 2033694 BACKGROUND

• Thrasher JB, Kreder KJ, Peterson NE, Donatucci CF. Lidocaine as topical anesthesia for bladder mappings and cold-cup biopsies. J Urol. 1993 Aug;150(2 Pt 1):335-6. doi: 10.1016/s0022-5347(17)35477-0.

  PMID: 8326556 BACKGROUND

• Birch BR, Miller RA. Absorption characteristics of lignocaine following intravesical instillation. Scand J Urol Nephrol. 1994 Dec;28(4):359-64. doi: 10.3109/00365599409180513.

  PMID: 7886411 BACKGROUND

• El Issaoui M, Elmelund M, Klarskov N. Alkalinised lidocaine as an anaesthetic before onabotulinumtoxinA injections. a randomised trial. BJU Int. 2025 Apr;135(4):638-647. doi: 10.1111/bju.16647. Epub 2025 Jan 11.

  PMID: 39797697 DERIVED

Related Links

• Abrams P, Cardozo, L, Wagg, A, Wein, A. (Eds) Incontinence 6th Edition. International Continence Society, Bristol UK,: ICI-ICS.; 2017
• Incontinence. International Consultation on Incontinence: ICUD; 2017

MeSH Terms

Conditions

Urinary Incontinence, Urge; Urinary Bladder, Overactive; Pain, Procedural; Urinary Tract Infections; Hematuria

Condition Hierarchy (Ancestors)

Urinary Incontinence; Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Urinary Bladder Diseases; Pain; Neurologic Manifestations; Infections; Hemorrhage; Pathologic Processes

Study Officials

• Niels Klarskov, Prof,MD,DMSc

  Herlev and Gentofte Hospital, University of Copenhagen

  STUDY DIRECTOR

Central Study Contacts

Meryam El Issaoui, MD

CONTACT

+4553252379; meryam.el.issaoui.01@regionh.dk

Niels Klarskov, Prof,MD,DMSc

CONTACT

+4538681406; niels.klarskov@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Region Hovedstadens Apotek, Herlev Hospital produces the Lidocaine solution and the matching placebo solution, performs the randomization, and packages the blinded dosing kits with the order of Lidocaine and placebo in a balanced design (50% Lidocaine at the first treatment). Participants will get consecutive randomization numbers, which specify the dosing kit. Neither the participant, the operator, or the healthcare professional interviewing the participant about her pain score know what solution the participant gets administered.
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD Student

Model Details: The study is a randomized, controlled, double-blinded, crossover study. The participants are their own control in the evaluation of the effect of intravesical alkalinized Lidocaine solution versus placebo as anesthesia prior to intravesical injection of onabotulinum toxin A. The chosen model is advantageous as a smaller sample size is needed, and error variance is reduced.

Study Record Dates

• First Submitted: June 8, 2022
• First Posted: June 13, 2022
• Study Start: September 12, 2022
• Primary Completion: April 1, 2024
• Study Completion: May 1, 2024
• Last Updated: September 22, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)