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

Sponsor

Herlev and Gentofte Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05415865

Collaborator

Region Hovedstadens Apotek (Other)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Urge Incontinence Overactive Bladder Anesthesia, Local Pain, Procedural Urinary Tract Infections Hematuria	Combination Product: Alkalinized Lidocaine Drug: Placebo Sodium Chloride 0.9% Inj	Phase 3

Detailed Description

The aim of the study is to investigate if bladder installed Lidocaine solution have an effect on reported pain during BTX-A injections compared to placebo.

The study participants will be recruited from the existing patient populations enrolled in the BTX-A program of the tertiary Urogynaecological Clinic of Herlev University Hospital.

The participants are randomized to:

Active drug: Lidocaine Hydrochloride and Sodium hydrogen carbonate
Placebo: Sodium Chloride

The study includes 5 study visits:

Visit 1:

First treatment day
Randomization
Registration of pre-treatment pain relief medications: paracetamol, ibuprofen, or other medications. If pre-treatment pain relief is taken before first treatment, same pain relief should be taken before second treatment day (visit 4) in order to reduce bias
Registration of antibiotic treatment: current antibiotic treatment or long-term prophylactic antibiotic for prevention of recurrent UTI The participant receives the active treatment or placebo, double-blinded
The participant is asked to grade the intensity of pain according to VAS score immediately after, and when participant has been dressed after the BTX-A injections

Visit 2 (by telephone):

Phone consultation 1 week after treatment:
The participant's experience on the procedure on a 5-point ordinal scale: "1- very unsatisfied", "2- unsatisfied", "3- neither unsatisfied or satisfied", "4- satisfied", "5-very satisfied"

Side effects:

Questions on symptoms of UTI: dysuria, cloudy urine, pollakiuria, nocturia
Hematuria
Inability to empty the bladder
Other symptoms

(Visit 3:)

The participant contacts the Clinic for next treatment approximately 6-12 months later
Sponsor or investigator from the Urogynecological Clinic reach out for the participant asking on symptoms of UUI if the participant has not contacted the clinic within 12 months

Visit 4:

Second treatment day
The participant receives the opposite treatment, still double-blinded
Registration of pre-treatment pain relief medications: paracetamol, ibuprofen, or other medications
Registration of antibiotic treatment: current antibiotic treatment or long-term prophylactic antibiotic for prevention of recurrent UTI
The participant is asked to grade the intensity of pain according to VAS score immediately after, and when participant has been dressed after the BTX-A injections

Visit 5(by telephone):

Phone consultation 1 week after treatment:
The participant's experience on the procedure on a 5-point scale: "1- very unsatisfied", "2- unsatisfied", "3- neither unsatisfied or satisfied", "4- satisfied", "5-very satisfied"

Side effects:

Questions on symptoms of UTI: dysuria, cloudy urine, pollakiuria nocturia,
Hematuria
Inability to empty the bladder
Other symptoms

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

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.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.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

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.

Primary Purpose:

Supportive Care

Official Title:

The Effect of Intravesical Lidocaine Solution Versus Placebo as Anesthesia Prior to Intravesical Injection of Onabotulinum Toxin A. A Randomized, Double-blind, Placebo Controlled Cross-over Study

Anticipated Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Apr 1, 2024

Anticipated Study Completion Date :

May 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Alkalinized Lidocaine, then Placebo 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 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. Drug: Placebo Sodium Chloride 0.9% Inj 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.
Active Comparator: Placebo, then Alkalinized Lidocaine 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 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. Drug: Placebo Sodium Chloride 0.9% Inj 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.

Arm

Intervention/Treatment

Active Comparator: Alkalinized Lidocaine, then Placebo

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

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.

Drug: Placebo Sodium Chloride 0.9% Inj

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.

Active Comparator: Placebo, then Alkalinized Lidocaine

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

Outcome Measures

Primary Outcome Measures

100 mm Visual Analogue Scale (VAS) score [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]
The maximum pain score reported by using VAS

Secondary Outcome Measures

Post-void residual requiring Clean Intermittent Catheterization (CIC) [Phone consultation one week after each treatment]
The participant is contacted after each treatment and asked about any inability to empty the bladder
Urinary tract infection (UTI) [Phone consultation one week after each treatment]
The participant is contacted after each treatment and asked about symptoms of UTI: Dysuria, cloudy urine, pollakiuria, nocturia
Hematuria [Phone consultation one week after each treatment]
The participant is contacted after each treatment and asked about blood in the urine
5-point rating scale [Phone consultation one week after each treatment]
The participant is contacted one week after every treatment and asked about the experience on the procedure. The participant's experience on the procedure on a 5-point ordinal scale: "1- very unsatis-fied", "2- unsatisfied", "3- neither unsatisfied or satisfied", "4- satisfied", "5-very satisfied"

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion criteria:

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

Exclusion criteria:

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