Clinical trial NCT05308979: Intradetrusor Botulinum Toxin A for OAB Via 1 Versus 10 Injections: A Randomized Clinical Trial
Official title: Intradetrusor Botulinum Toxin A for OAB Via 1 Versus 10 Injections: A Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Overactive Bladder
Urinary Urge Incontinence
Overactive Bladder Syndrome
Urinary Incontinence, Urge
Urge Incontinence
Urinary Urgency
Urinary Frequency
Lead sponsor: University of California, Irvine
Sponsor class: OTHER
Collaborators: name: Kaiser Permanente
name: St. Joseph Hospital of Orange
First posted: 2022-04-04
Enrollment: 116
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel study with 2 arms, 1:1 randomization
Primary purpose: TREATMENT

Brief summary: Patients with either overactive bladder (OAB) or urgency urinary incontinence (UUI) with be randomized (like a flip of a coin) to receive 100 units of bladder Botox® at either one injection site or ten injection sites. Efficacy and patient satisfaction will be measured by questionnaires.

Detailed description: Intradetrusor (bladder) Botulinum toxin A (BTA or Botox®) is a well-established treatment for urinary urgency incontinence (UUI).\[1,2\] While this treatment's efficacy in comparison to alternative therapies including anticholinergic medications and sacral neuromodulation for treatment of UUI has been studied, the ideal number of injection sites within the bladder has not been well established. \[3,4\] Intradetrusor BTA injections are often completed as an office procedure while the patient is awake. Each injection site can cause discomfort for the patient during the procedure. Urinary tract infection and urinary retention are risks associated with this procedure and could potentially be related to number of injection sites. Currently, there is a lack of information in the literature regarding the optimal number of intravesical BTA injection sites.

Prior studies evaluated efficacy using 100u BTA spread across 20 injections sites, however current practices at local institutions safely use 10 injections sites based on studies showing similar effect and adverse event profiles between use of 10, 20, and 40 injection sites.\[5,6\] Research using animal models has shown diffuse distribution of BTA within the entire detrusor muscle after just a single BTA injection at one site.\[7\] This has been corroborated in human studies.\[8\] A recently published observational pilot study shows promise for single site intradetrusor Botox® injection as it reported a lower rate of urinary retention and similar durability.\[9\] Similar clinical efficacy with only one to three intravesical BTA injection\[s\] has also been reported.\[10\]

In this study, participants will be randomized to receive 100u BTA via intradetrusor injection at one injection site (experimental) versus 10 injection sites (control). Investigators hypothesize that one injection will have similar efficacy to multiple injections and potentially better tolerability and patient satisfaction, due to decreased procedure time and less pain, along with potential for lower adverse event rates, specifically urinary retention and urinary tract infections.

Eligibility criteria: Inclusion Criteria:

* Female
* 18 years old or greater
* Diagnosis of overactive bladder (urinary urgency or frequency, OAB) or urinary urgency incontinence (UUI)

Exclusion Criteria:

* Have a diagnosis of neurogenic bladder
* Received intravesical botox injections within prior 6 months
* Current treatment with either: SNM, PTNS, or OAB medications - need wash out as below
* SNM - turn device off for at least 2 weeks prior to procedure, off during 3-month follow up window
* PTNS - no treatments within 2 weeks of start, none during 3-month post-procedure follow up window
* OAB meds - 2 week wash out period prior to injection, none during 3-month post-procedure follow up window
* Currently pregnant or trying to get pregnant
* Contraindications to Botox® - hypersensitivity to Botox®, inability to self-catheterize/refusal to have indwelling catheter
* Have a UTI (can enroll after treatment)
* Have urinary retention (PVR\>150cc on two occasions)
* Do not speak English or Spanish

Primary outcomes:
measure: Change in Overactive Bladder Questionnaire Long Form Score (Symptoms Severity Sub-scale)(OAB-Q LF)
timeFrame: change from baseline OAB-Q score to 3 wk post-procedure score
Secondary outcomes:
measure: Change in Overactive Bladder Questionnaire Long Form Score (Symptoms Severity Sub-scale)(OAB-Q LF)
timeFrame: comparison of baseline OAB-Q score to 3 month post-procedure score
measure: Post-void Residual (PVR)
timeFrame: PVR collected at 3 wk post-procedure
measure: Number of Participants With Urinary Tract Infection (UTI)
timeFrame: anytime after procedure, until at least 3 months post-procedure.
measure: Patient Global Impression - Improvement (PGI-I)
timeFrame: 3 months after botox procedure
measure: Visual Analogue Scale (VAS) - Pain
timeFrame: immediately after procedure
Other outcomes:
Locations:
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
Study officials:
affiliation: UC Irvine
name: Carly Crowder, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UC Irvine
name: Taylor Brueseke, MD
role: STUDY_DIRECTOR
affiliation: UC Irvine
name: Felicia Lane, MD
role: STUDY_CHAIR
References:
citation: Brubaker L, Richter HE, Visco A, Mahajan S, Nygaard I, Braun TM, Barber MD, Menefee S, Schaffer J, Weber AM, Wei J; Pelvic Floor Disorders Network. Refractory idiopathic urge urinary incontinence and botulinum A injection. J Urol. 2008 Jul;180(1):217-22. doi: 10.1016/j.juro.2008.03.028. Epub 2008 May 21.
citation: Chapple C, Sievert KD, MacDiarmid S, Khullar V, Radziszewski P, Nardo C, Thompson C, Zhou J, Haag-Molkenteller C. OnabotulinumtoxinA 100 U significantly improves all idiopathic overactive bladder symptoms and quality of life in patients with overactive bladder and urinary incontinence: a randomised, double-blind, placebo-controlled trial. Eur Urol. 2013 Aug;64(2):249-56. doi: 10.1016/j.eururo.2013.04.001. Epub 2013 Apr 10.
citation: Visco AG, Brubaker L, Richter HE, Nygaard I, Paraiso MF, Menefee SA, Schaffer J, Lowder J, Khandwala S, Sirls L, Spino C, Nolen TL, Wallace D, Meikle SF; Pelvic Floor Disorders Network. Anticholinergic therapy vs. onabotulinumtoxina for urgency urinary incontinence. N Engl J Med. 2012 Nov 8;367(19):1803-13. doi: 10.1056/NEJMoa1208872. Epub 2012 Oct 4.
citation: Amundsen CL, Richter HE, Menefee SA, Komesu YM, Arya LA, Gregory WT, Myers DL, Zyczynski HM, Vasavada S, Nolen TL, Wallace D, Meikle SF. OnabotulinumtoxinA vs Sacral Neuromodulation on Refractory Urgency Urinary Incontinence in Women: A Randomized Clinical Trial. JAMA. 2016 Oct 4;316(13):1366-1374. doi: 10.1001/jama.2016.14617.
citation: 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.
citation: Liao CH, Chen SF, Kuo HC. Different number of intravesical onabotulinumtoxinA injections for patients with refractory detrusor overactivity do not affect treatment outcome: A prospective randomized comparative study. Neurourol Urodyn. 2016 Aug;35(6):717-23. doi: 10.1002/nau.22780. Epub 2015 Apr 24.
citation: Coelho A, Cruz F, Cruz CD, Avelino A. Spread of onabotulinumtoxinA after bladder injection. Experimental study using the distribution of cleaved SNAP-25 as the marker of the toxin action. Eur Urol. 2012 Jun;61(6):1178-84. doi: 10.1016/j.eururo.2012.01.046. Epub 2012 Feb 1.
citation: Mehnert U, Boy S, Schmid M, Reitz A, von Hessling A, Hodler J, Schurch B. A morphological evaluation of botulinum neurotoxin A injections into the detrusor muscle using magnetic resonance imaging. World J Urol. 2009 Jun;27(3):397-403. doi: 10.1007/s00345-008-0362-0. Epub 2009 Jan 15.
citation: Ton J, Downing P, Versi E, van Uem S, Ephraim S, Murphy M, Lucente V. Outcomes of a single trigone-only vs. 20 trigone-sparing injections of OnabotulinumtoxinA for refractory overactive bladder (OAB). Int Urol Nephrol. 2021 Jun;53(6):1067-1072. doi: 10.1007/s11255-021-02802-0. Epub 2021 Mar 19.
citation: Avallone MA, Sack BS, El-Arabi A, Guralnick ML, O'Connor RC. Less is more-A pilot study evaluating one to three intradetrusor sites for injection of OnabotulinumtoxinA for neurogenic and idiopathic detrusor overactivity. Neurourol Urodyn. 2017 Apr;36(4):1104-1107. doi: 10.1002/nau.23052. Epub 2016 Jun 10.