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

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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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

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

Intervention / Treatment
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* Combination Product: Alkalinized Lidocaine
* Drug: Placebo Sodium Chloride 0.9% Inj


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional 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.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Alkalinized Lidocaine, then Placebo<br>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<br>* 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.<br>Drug: Placebo Sodium Chloride 0.9% Inj<br>* 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.<br>|
| Active Comparator: Placebo, then Alkalinized Lidocaine<br>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<br>* 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.<br>Drug: Placebo Sodium Chloride 0.9% Inj<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-void residual requiring Clean Intermittent Catheterization (CIC) | The participant is contacted after each treatment and asked about any inability to empty the bladder | Phone consultation one week after each treatment | 
| Urinary tract infection (UTI) | The participant is contacted after each treatment and asked about symptoms of UTI: Dysuria, cloudy urine, pollakiuria, nocturia | Phone consultation one week after each treatment | 
| Hematuria | The participant is contacted after each treatment and asked about blood in the urine | Phone consultation one week after each treatment | 
| 5-point rating scale | 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 | Phone consultation one week after each treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Urge incontinence, Anesthesia, Local, Botulinum Toxins, Type A, Overactive Bladder, Alkalinized Lidocaine, Double-blind Method, Visual Analog Scale, Administration, Intravesical