Evaluation of Intradetrusor AbobotulinumtoxinA and IncobotulinumtoxinA in Women With Overactive Bladder

Evaluation of Intradetrusor AbobotulinumtoxinA and IncobotulinumtoxinA Efficacy and Safety in Women With Overactive Bladder and Urge Urinary Incontinence and the Value of Local Anesthesia for Pain Reduction

A randomized, single blind, non-inferiority clinical study was performed evaluating the efficacy and safety of AbobotulinumtoxinA vs. IncobotulinumtoxinA intradetrusor injections in women with overactive bladder and urge urinary incontinence. Also the effect of local anesthesia on pain level of the procedure was assessed.

Study Overview

• Status: Completed
• Conditions: Overactive Bladder
• Intervention / Treatment: Drug: AbobotulinumtoxinA 300 UNT; Drug: Lidocain; Other: placebo; Drug: IncobotulinumtoxinA 100 UNT

Detailed Description

In the described prospective, clinical trial, approved by the National Medical Ethics Committee (protocol number: 0120-44/2018/5; date of approval: 22/02/2018), female patients were enrolled, followed by signed informed consent.

Before treatment patients underwent history and physical examination. Before botulinum toxin injection each patient completed three questionnaires, UDI-6 (Urogenital Distress Inventory), IIQ-7 (Incontinence Impact Questionnaire), I-QOL (Incontinence Quality of Life). The total score of each questionnaire was considered. Before botulinum toxin injection, urinalysis was performed to check for a urinary tract infection (UTI). For those presenting with UTI, treatment was postponed until the UTI was treated and a repeat urinalysis was performed. Nitrofurantoin 100 mg twice daily per os was given prophylactically on the day of the procedure. Patients were randomised to receive either 300 units of AbobotulinumtoxinA (Dysport®) or 100 units of IncobotulinumtoxinA (Xeomin®). They were further randomised to receive local anesthesia or placebo. 30 minutes before the procedure the bladder was instilled with either 40 ml 1% lidocaine solution using a 16Fr urethral Foley catheter or with 40 ml 0.9% NaCl solution. All patients received urethral lubrication gel. Using rigid cystoscopy, normal saline was used to dilute the vial to 20 ml. A total of 20 evenly distributed intradetrusor injections, 1 ml per site, were performed, 2 of them included the trigone area. During the procedure the patients graded the pain level of every injection on a Visual Analog Scale (VAS). All patients were treated in an outpatient clinic and by one experienced surgeon.

After 1 to 2 weeks patients were seen for evaluation of systemic side effects, physical examination, measurement of residual urine and urinalysis to eventually diagnose and treat a urinary tract infection. After 4 months patients were seen to evaluate the treatment result and complete the questionnaires, IIQ-7, UDI-6, patient satisfaction survey and I-QOL. Side effects were monitored for 5 months after the procedure.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 4

Contacts and Locations

Study Locations

• Slovenia
  • Maribor, Slovenia, 2000
    • University Medical Centre Maribor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• female, age between 18 and 90, presence of urinary urgency with urgency urinary incontinence, residual urine below 150 ml, previous non-pharmacological conservative treatments (e.g., pelvic floor muscle training) inefficiency, anticholinergic or beta-3 agonist treatment inefficiency.

Exclusion Criteria:

• patients that already have received treatment with botulinum toxin, pregnancy or breast- feeding and any diseases or functional abnormalities that might affect bladder function. Patients with stress urinary incontinence.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: AbobotulinumtoxinA and lidocaine; The bladder was instilled with 40 ml of 1% lidocaine solution using a 16Fr urethral Foley catheter. 30 minutes afterwards patients received 300 units of AbobotulinumtoxinA using rigid cystoscopy. Normal saline was used to dilute the vial to 20 ml. A total of 20 evenly distributed intradetrusor injections, 1 ml per site, were performed, 2 of them included the trigone area.	Drug: AbobotulinumtoxinA 300 UNT; 20 evenly distributed intradetrusor injections, 1 ml per site, were performed; Drug: Lidocain; 30 minutes before the procedure the bladder was instilled with 40 ml of 1% lidocaine solution using a 16Fr urethral Foley catheter
Other: AbobotulinumtoxinA and placebo; The bladder was instilled with 40 ml of 0.9% NaCl solution using a 16Fr urethral Foley catheter. 30 minutes afterwards patients received 300 units of AbobotulinumtoxinA using rigid cystoscopy. Normal saline was used to dilute the vial to 20 ml. A total of 20 evenly distributed intradetrusor injections, 1 ml per site, were performed, 2 of them included the trigone area.	Drug: AbobotulinumtoxinA 300 UNT; 20 evenly distributed intradetrusor injections, 1 ml per site, were performed; Other: placebo; 30 minutes before the procedure the bladder was instilled with 40 ml of 0.9% NaCl solution
Other: IncobotulinumtoxinA and lidocaine; The bladder was instilled with 40 ml of 1% lidocaine solution using a 16Fr urethral Foley catheter. 30 minutes afterwards patients received 100 units of IncobotulinumtoxinA using rigid cystoscopy. Normal saline was used to dilute the vial to 20 ml. A total of 20 evenly distributed intradetrusor injections, 1 ml per site, were performed, 2 of them included the trigone area.	Drug: Lidocain; 30 minutes before the procedure the bladder was instilled with 40 ml of 1% lidocaine solution using a 16Fr urethral Foley catheter; Drug: IncobotulinumtoxinA 100 UNT; 20 evenly distributed intradetrusor injections, 1 ml per site, were performed
Other: IncobotulinumtoxinA and placebo; The bladder was instilled with 40 ml of 0.9% NaCl solution using a 16Fr urethral Foley catheter. 30 minutes afterwards patients received 100 units of IncobotulinumtoxinA. using rigid cystoscopy. Normal saline was used to dilute the vial to 20 ml. A total of 20 evenly distributed intradetrusor injections, 1 ml per site, were performed, 2 of them included the trigone area.	Other: placebo; 30 minutes before the procedure the bladder was instilled with 40 ml of 0.9% NaCl solution; Drug: IncobotulinumtoxinA 100 UNT; 20 evenly distributed intradetrusor injections, 1 ml per site, were performed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of Intradetrusor AbobotulinumtoxinA and IncobotulinumtoxinA	Questionnaire scores of UDI-6 (Urogenital Distress Inventory), IIQ-7 (Incontinence Impact Questionnaire) and I-QOL (Incontinence Quality of Life) will be evaluated before and after the procedure for non-inferiority of the two drugs.	5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Value of Local Anesthesia for Pain Reduction	During the procedure the patients graded the pain level of every injection on a Visual Analog Scale (VAS). The total score of each questionnaire will be evaluated for non-inferiority of placebo in comparison to local anesthesia.	The day of procedure
Safety of Intradetrusor AbobotulinumtoxinA and IncobotulinumtoxinA	Frequency of adverse events (urinary retention, urinary tract infection)	5 months

Collaborators and Investigators

• Sponsor: Niko Kavcic
• Investigators: Principal Investigator: Niko Kavčič, MD, University Medical Centre Maribor

Publications and helpful links

General Publications

• Giannantoni A, Gubbiotti M, Rubilotta E, Balzarro M, Antonelli A, Bini V. IncobotulinumtoxinA versus onabotulinumtoxinA intradetrusor injections in patients with neurogenic detrusor overactivity incontinence: a double-blind, randomized, non-inferiority trial. Minerva Urol Nephrol. 2022 Oct;74(5):625-635. doi: 10.23736/S2724-6051.21.04227-2. Epub 2021 Mar 26.
• Lange S, Koch M, Lange R, Husslein H, Umek W, Bodner-Adler B. Perioperative Techniques for the Use of Botulinum Toxin in Overactive Bladder: Results of a Multinational Online Survey of Urogynecologists in Germany, Austria, and Switzerland. J Clin Med. 2023 Feb 12;12(4):1462. doi: 10.3390/jcm12041462.

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2018
• Primary Completion (Actual): November 25, 2022
• Study Completion (Actual): November 25, 2022

Study Registration Dates

• First Submitted: January 18, 2024
• First Submitted That Met QC Criteria: January 31, 2024
• First Posted (Actual): February 9, 2024

Study Record Updates

• Last Update Posted (Actual): February 12, 2024
• Last Update Submitted That Met QC Criteria: February 8, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: overactive bladder; botulinum toxin; local anesthesia; abobotulinumtoxinA; incobotulinumtoxinA
• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder, Overactive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Cholinergic Agents; Sensory System Agents; Anesthetics; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Acetylcholine Release Inhibitors; Neuromuscular Agents; Lidocaine; Botulinum Toxins, Type A; abobotulinumtoxinA; incobotulinumtoxinA
• Other Study ID Numbers: IRP-2018-01-14

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We intend to publish a research article in 2024. All supporting information will be shared with the journal.
• IPD Sharing Time Frame: We intend to publish a research article in 2024. All supporting information will be shared with the journal.
• IPD Sharing Access Criteria: Access will be provided by the journal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No