Trigonal vs Non Trigonal Botox Injection in OAB.

Trigonal-sparing Versus Trigonal-involved Intravesical Botulinumtoxin A Injection in Refractory Idiopathic Detrusor Overactivity.

The investigators attend to conduct a prospective randomized study to assess safety and efficacy of trigonal-involved vs. trigonal-sparing botox injection technique, quality of life measurement and post-injection anticholinergics use efficacy.

Assessing safety by identification of side effects like constipation, urine retention....etc.

efficacy is measured using Over Active Bladder Symptoms Score(OABSS) and urodynamics measures after 6 months follow up.

Study Overview

• Status: Completed
• Conditions: Quality of Life; Urologic Diseases; Overactive Bladder Syndrome; Anticholinergic Syndrome
• Intervention / Treatment: Drug: botulinum toxin A

Detailed Description

Overactive bladder (OAB) is a condition characterized by the presence of urinary urgency, typically joined by frequency and nocturia, with or without urgency urinary incontinence [UUI], in the absence of urinary tract infection (UTI) or other clear pathology.

Frequency is the most commonly reported symptom coming to 85% while 54% complained of urgency and 36% urgency incontinence.

OAB has usually resulted from detrusor over activities. The basic cause could be a neurological disorder (neurogenic type) such as spinal cord injuries, multiple sclerosis. In some cases, no obvious cause could be identified (idiopathic type).

OAB is a prevalent, chronic symptom complex that can impair quality of life (QOL). The prevalence of OAB in the general population was evaluated at 11.8% in a population-based survey conducted across five European countries. Epidemiological studies from North America have reported prevalence of OAB in women of 16.9% and the prevalence increases with age rising to 30.9% in those beyond 65 years.

Treatment objectives are to reduce the occurrence of bothersome symptoms. Several treatment choices are available for OAB including bladder and behavioral training, pharmacologic treatment, and surgical treatment.

Antimuscarinics are well established as pharmacotherapy for reducing OAB symptoms and enhancing QOL.Although, their use is limited in some patients by insufficient response to treatment "refractory OAB", or intolerable side effects , for example , dry mouth , blurred vision , constipation and cognitive impairment.

More recently, a European and Australian trial including about 2000 patients assessed mirabegron (β-3 agonist) (50 mg and 100 mg) in comparison to tolterodine (4 mg ER preparation) and placebo. There was a significant reduction in the number of voids over a 24-hours period, and incontinence episodes, vs. placebo at 12 weeks, at 1.93 vs. 1.34 (P < 0.05) and 1.57 vs. 1.17 (P < 0.05), respectively.

After a trial of pharmacotherapy, if the patient has not had satisfactory improvement in symptoms, intra-vesicle injection of Botox (BTX) can be offered as the following step.

Botulinum toxin (BTX) is a neurotoxin, it contains a heavy chain that binds to the presynaptic terminal of the neuromuscular junction , and this then acts by inhibiting the release of acetylcholine from the presynaptic vesicles at the axon terminal of the motor end plate , that then results in the muscle that is innervated becoming flaccidly paralyzed. BTX is available in different preparations. The current commercially utilized type is BTX type A.

Now, there is cumulative data supporting use of BTX in cases of refractory Detrusor overactivity (DO).

Intradetrusal injection of BTX is followed by a significant improvements in the number of voiding episodes over 24 hours, incontinence episodes, urodynamic variables and quality of life scores. There is a decrease in episodes of urgency and incontinence by 80% and 60%, respectively. The efficacy peaks at 4 weeks, with the effect lasting typically up to 9 months.

Some essential issues for further investigations are the injection site, volume and number of injections. In terms of dosage, there are no firm recommendations, but in practice the advice was for a lower starting dose of 100 units of BTX-A, based on the currently available research. The disadvantage with higher dosing is the reduction in detrusor voiding pressures and an increased risk of voiding problems, while at the same time there is no increased efficacy.

The current AUA and EUA guidelines recommend trigonal sparing technique. During the injection process the trigone is typically spared because of the theoretical risk of de novo VUR from inhibition of the peritrigonal anti-reflux mechanism.

Moreover, trigonal area is rich in sensory fibers, therefore trigonal injection may enhance sensory component of urgency.

• Study Type: Interventional
• Enrollment (Actual): 80
• 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: All

Description

Inclusion Criteria:

• Patients with idiopathic OAB refractory to treatment with antimuscarinics for 2 months or intolerable side effects of antimuscrinics

Exclusion Criteria:

• Patients who have any of the following were excluded:

  • Age less than 18 year old.
  • Neurogenic detrusor overactivity.
  • Evidence of obstructed flow in absence of prolapse.
  • Mixed urinary incontinence
  • Associated urethral pathology, e.g. Urethral diverticulum
  • Associated bladder pathology e.g. Fistula.
  • Active urinary tract infection as evidenced by positive urine culture.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: trigonal sparing botox injection; Using a 7 gauge needle injection were allocated uniformly and evenly throughout the designed area excluding trigone in other arm Dilution of BOTOX vial (100 u) in 10 ml normal saline (10 u/ml) and injected in 20 sites (0.5ml /site).•then after 6 months postoperative anticholinergics administration .	Drug: botulinum toxin A; botox A injection trigonal or trigonal sparing with trial of anticholinergics 6 months post operative for 3 months; Other Names: anticholinergics
Active Comparator: trigonal involved; Using a 7 gauge needle injection were allocated uniformly and evenly throughout the designed area including the trigone .Dilution of BOTOX vial (100 u) in 10 ml normal saline (10 u/ml) and injected in 20 sites (0.5ml /site).then after 6 months postoperative anticholinergics administration .	Drug: botulinum toxin A; botox A injection trigonal or trigonal sparing with trial of anticholinergics 6 months post operative for 3 months; Other Names: anticholinergics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
efficacy of Botox injections of the bladder treating OAB using Over active bladder Symptoms score (OABSS).OABSS total score is 15.more score means more symptoms.it is divided into:1-5 &6-10&11-15 means mild &moderate&sever symptoms respectively.	Over active bladder symptoms score (OABSS).	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
efficacy of anticholinergics post botox injection using Over active bladder symptoms score (OABSS).	Over active bladder symptoms score (OABSS).OABSS total score is 15.more score means more symptoms.it is divided into:1-5 &6-10&11-15 means mild &moderate&sever symptoms respectively.	3 months
quality of life assessment of patients with anticholinergics alone vs patients with botox injections vs combined therapy.	I-QOL Questionnaire	3 months
Arabic validation of overactive bladder symptoms score	To validate and translate English form to Arabic version of the over active bladder symptoms score (OABSS)	3 months

Collaborators and Investigators

• Sponsor: Mansoura University
• Investigators: Study Chair: Ahmed Shoma, MD, Urology and Nephrology Cente. Mansourah, Aldakahlia, Egypt, 35516

Publications and helpful links

General Publications

• Elbaset MA, Hashem A, Taha DE, Zahran MH, El-Hefnawy AS. Validation of the Arabic linguistic version of the Overactive Bladder Symptoms Score questionnaire. Arab J Urol. 2019 Jun 12;17(4):265-269. doi: 10.1080/2090598X.2019.1627061. eCollection 2019.

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2015
• Primary Completion (Actual): October 30, 2016
• Study Completion (Actual): May 30, 2018

Study Registration Dates

• First Submitted: April 29, 2018
• First Submitted That Met QC Criteria: May 10, 2018
• First Posted (Actual): May 22, 2018

Study Record Updates

• Last Update Posted (Actual): October 9, 2018
• Last Update Submitted That Met QC Criteria: October 5, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: OAB , Botox , anticholinergics , quality of life
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Disease; Drug-Related Side Effects and Adverse Reactions; Urinary Bladder, Overactive; Syndrome; Urologic Diseases; Anticholinergic Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA; Cholinergic Antagonists
• Other Study ID Numbers: OAB Botox injection

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