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Bladder Instillations Versus Onabotulinumtoxin A for Treatment of Interstitial Cystitis/Bladder Pain Syndrome

NCT04401176 — Phase 2, Completed, 58 participants, Walter Reed National Military Medical Center
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A Randomized Trial of Bladder Instillations Versus Onabotulinumtoxin A for Treatment of Interstitial Cystitis/Bladder Pain Syndrome

RegistryNCT04401176
StatusCompleted
PhasePhase 2
Study typeInterventional; randomized, parallel, masking: none, treatment
Enrollment58 (Actual)
SponsorWalter Reed National Military Medical Center (Fed)
ConditionsInterstitial Cystitis, Bladder Pain Syndrome
InterventionsHeparin & Alkalinized Lidocaine Bladder Instillation, Onabotulinum Toxin A (Drug)
Datesstart 2020-09-15, primary completion 2023-06-01, completion 2023-06-01, first posted 2020-05-26, last updated 2023-10-12
Locations1 site in United States

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-Summary

Recognition of interstitial cystitis (IC)/bladder pain syndrome (BPS) is increasing. There is a dire need to develop effective treatment options for these patients as it manifests as more than a physical disease, affecting general and psychological health as well. Existing trials comparing varying bladder instillation formulations have not identified an optimal bladder instillation therapy, however existing studies support combined heparin and alkalinized lidocaine bladder instillation as an affordable and effective treatment for IC/BPS. Additionally, intradetrusor onabotulinumtoxinA injection has been well established for the treatment of overactive bladder (OAB), a constellation of symptoms similar to that of IC/BPS. OnabotulinumtoxinA has now come into the forefront for treatment of OAB due to its efficacy, safety profile, and absence of cognitive effects related to the previous mainstay anticholinergic treatment. While both bladder instillation and onabotulinumtoxinA therapy have been shown to be effective for treatment of IC/BPS, a direct comparison of these treatments has not been performed. We therefore designed a randomized controlled trial to compare the efficacy of heparin with alkalized local anesthetic bladder instillation versus intradetrusor onabotulinumtoxinA injection in treating IC/BPS symptoms.

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+Arms and interventions

ArmTypeInterventionsDescription
Heparin & Alkalinized Lidocaine Bladder InstillationActive comparatorDrug: Heparin & Alkalinized Lidocaine Bladder InstillationSix weekly bladder instillations, each instillation consisting of 40,000 IU Heparin, 200mg lidocaine, 2ml 8.4% sodium bicarbonate, sterile water for a total volume 50 milliliters (mL).
Intradetrusor Onabotulinumtoxin A InjectionActive comparatorDrug: Onabotulinum Toxin A100 units onabotulinumtoxinA reconstituted in 10mL of injectable saline, injected in 20 sites with 0.5mL per injection along the posterior wall of the bladder above the trigone.
  • Heparin & Alkalinized Lidocaine Bladder Instillation (Drug): Bladder instillation instilled via catheter and to dwell for minimum of 30 minutes prior to spontaneous void
  • Onabotulinum Toxin A (Drug): Intradetrusor onabotulinumtoxinA injection (0.5mL x 20 sites)

+Outcome measures

Primary outcomes

  • Change in O'Leary-Sant questionnaire scores from baseline between bladder instillation and intradetrusor onabotulinumtoxinA injection groups [Baseline, 8-10 weeks]: Consists of O'Leary-Sant Symptom and Problem Index, total score 0-36.

Secondary outcomes

  • Change in O'Leary-Sant questionnaire scores from baseline between bladder instillation and intradetrusor onabotulinumtoxinA injection groups [Baseline, 4-6 weeks, 6-9 months]: Consists of O'Leary-Sant Symptom and Problem Index. Total score 0-36
  • Change in pain scores using the Defense and Veterans Pain Rating Scale (visual analog scale) between bladder instillation and intradetrusor onabotulinumtoxinA injection groups [Baseline, 4-6 weeks, 8-10 weeks, 6-9 months]: Scale of 0-10 (0= no pain, 10 = worst pain)
  • Change in Female Sexual Function Index (FSFI) score between bladder instillation and intradetrusor onabotulinumtoxinA injection groups [Baseline, 4-6 weeks, 8-10 weeks]: FSFI evaluates 5 domains of female sexual function including desire, arousal, lubrication, orgasm, satisfaction, and pain. Total score 2-36.
  • Change in Female Sexual Distress Scale-Revised (FSDS-R) score between bladder instillation and intradetrusor onabotulinumtoxinA injection groups [Baseline, 4-6 weeks, 8-10 weeks]: FSDS-R evaluates distress associated with inadequate/impaired sexual function. Total score 0-52.
  • Change in 12-item Short Form Survey (SF-12) score between bladder instillation and intradetrusor onabotulinumtoxinA injection groups [Baseline, 4-6 weeks, 8-10 weeks]: SF-12 is a general health questionnaire that evaluates quality of life measures, divided into mental and physical component scores.
  • Change in bladder capacity between bladder instillation and intradetrusor onabotulinumtoxinA injection groups [Baseline, 4-6 weeks, 8-10 weeks]: Bladder capacity via 1-day bladder diary
  • Incidence of adverse outcomes between bladder instillation and intradetrusor onabotulinumtoxinA injection groups [8-10 weeks]: Adverse outcomes to be defined specific to medication administered (urinary tract infection in both bladder instillation and onabotulinumtoxinA injection groups, urinary retention requiring catheterization, systemic effects related to onabotulinumtoxinA group only)
  • Patient perceptions of treatment between bladder instillation and intradetrusor onabotulinumtoxinA injection groups [6-9 months]: "How convenient or inconvenient was it to follow the treatment schedule as instructed?" (Scale 1-5 extremely inconvenient - extremely convenient) "How satisfied or dissatisfied are you in the ability of the treatment to treat your condition?" (Scale 1-5 extremely dissatisfied - extremely satisfied) "Taking all things into account, how satisfied or dissatisfied are you with this treatment?" (Scale 1-5 extremely dissatisfied - extremely satisfied) "How willing would you be to undergo this treatment again?" (Scale 1-5 extremely unwilling - extremely willing).
  • Incidence of re-treatment between bladder instillation and intradetrusor onabotulinumtoxinA injection groups [6-9 months]: Re-treatment defined as additional course or crossover treatment outside of assigned treatment group

+Eligibility

Sex: Female, ages: 18 Years to any

Inclusion Criteria:

* Females ≥ 18 years of age
* O'Leary-Sant questionnaire score ≥ 6
* Ability to follow study instructions and complete all required follow-up

Exclusion Criteria:

* Contraindications and/or allergies to medications used
* Known alternative diagnosis explaining bladder pain symptoms
* Bladder instillation within the past 3 months
* Intradetrusor onabotulinumtoxinA injection within the past 6 months
* Use of ≥ 400 units of onabotulinumtoxinA in the last 3 months
* Inability or unwillingness to self-catheterize
* Post-void residual > 200mL
* Concurrent procedural treatment (including hydrodistension, sacral neuromodulation)
* Current use of vaginal pessary/devices
* Untreated symptomatic prolapse > pelvic organ prolapse quantification system (POP-Q) stage 2
* Females who are pregnant or planning a pregnancy during the study or who think that they may be pregnant at the start of the study and who are unwilling or unable to use a reliable form of contraception during the study
* Inability to speak/read English

+Locations (1)

FacilityCityCountryStatus
Walter Reed National Military Medical CenterBethesda, MarylandUnited States

+Publications

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  • Results publication: Welch EK, Dengler KL, DiCarlo-Meacham AM, Wheat JE, Pekny CJ, Aden JK, Vaccaro CM. Bladder instillations vs onabotulinumtoxinA injection for interstitial cystitis/bladder pain syndrome: a randomized clinical trial. Am J Obstet Gynecol. 2024 Nov;231(5):528.e1-528.e11. doi: 10.1016/j.ajog.2024.05.027. Epub 2024 May 18. PMID 38768800

+Study documents

My Notes