Different Injection Number of the Same Dose of Botulinum Toxin A on Overactive Bladder Syndrome
Condition: Overactive Bladder
MeSH terms: Urinary Bladder, Overactive
Study type: Interventional
Phase: Phase 2

Summary: 
      Overactive bladder (OAB) is a symptom syndrome characterized by urgency frequency with or
      without urge urinary incontinence (UUI) that may affect the patients' quality of life.
      Current medical treatments are usually unsuccessful in completely eradicating urgency
      sensation. Intra-detrusor injection of botulinum toxin A (BoNT-A) modulates the release of
      neurotransmitters from sensory nerve endings and effectively modulates the inflammatory
      process mediated by nociceptive afferent nerve dysfunction. Satisfactory clinical results
      were achieved with intravesical BoNT-A injection, which increased bladder capacity and
      decreased urgency sensation in patients with neurogenic or idiopathic detrusor overactivity
      (NDO, IDO). Excellent results were achieved with injection of either 100 U or 200 U of
      BoNT-A. Episodes of frequency, urgency, and UUI were reduced, maximal cystometric capacity
      increased, maximal detrusor pressure (Pdet) decreased, and the quality of life index also
      improved significantly. However, post void residual (PVR) volume increased significantly and
      some patients required clean intermittent catheterization (CIC) to evacuate the PVR.
      Dose-related adverse events (AE) increased with increasing dose of BoNT-A. Therefore,
      adjustments of the BoNT-A dose and sites of injection might minimize the de novo AE and help
      to maintain success rates.
    

Detailed description: 
      This study was designed as a single blind, randomized, parallel, actively controlled trial.
      The urodynamic DO confirmed patients were randomly assigned to receive injection of
      onabotulinumtoxinA 100 U (BoNT-A, Allergan, Irvine, California, USA), which was reconstituted
      to 10 ml with normal saline for suburothelial injections, in one of the three groups with the
      following injection number: (A) 100 U in 10ml injections, 1.0ml for each injection, totally
      10 injections at bladder body (B) 100 U in 10ml, 0.5ml for each injection, totally 20
      injections at bladder body, (C) 100 U in 10ml, 0.25ml for each injection, totally 40
      injections at bladder body. Permuted block randomization was used for this trial. All
      treatments were evaluated at baseline and the primary end-point at 3 months.

      The inclusion criteria were patients of either gender, aged 20 years or more, with urodynamic
      DO and at least one episode of urgency (urgency severity scale, USS≥2) or UUI per day as
      recorded in the 3-day voiding diary. Patients with neurogenic bladder, urodynamically
      confirmed bladder outlet obstruction, prior pelvic surgery, anti-incontinence surgery or
      urinary tract infection (UTI, white blood cell(WBC)>10/high power field (HPF) in urinalysis)
      were excluded. Informed consent was obtained from all patients before randomization. This
      study should be approved by the Institution Review Board and Ethics Committee of the
      hospital.

      All patients had been managed with behavioral modification and treated with a certain number
      of antimuscarinics for more than 4 weeks before they were enrolled into this trial.
      Antimuscarinics was discontinued on the day of screening to wash out the remaining effect and
      obtaining a voiding diary that may reflect the true bladder condition.

      The injection method for each patient was not recorded in the operation note and the study
      nurse who controlled the outcome measures was blinded to the treatment assignment. All
      procedures were performed transurethrally under intravenous general anesthesia in the
      operation room. Anticoagulant was discontinued 1 week prior to onabotulinumtoxinA treatment.
      The bladder volume was kept at 100-150 ml and the blood vessels were avoided during
      injections. An indwelling Foley catheter was placed in the bladder overnight and the patients
      were discharged the next morning. Broad-spectrum prophylactic antibiotics were given
      postoperatively for 3 days. Patients who developed acute urinary retention (AUR) or PVR
      volumes greater than 250 ml were advised to perform CIC periodically to evacuate their
      bladders. The patients were monitored at the outpatient clinic regularly for upto 24 months
      until symptoms returned to baseline levels.

      Videourodynamic study was routinely performed at baseline, 3 and 6 months to measure
      urodynamic variables and detecting vesicoureteral reflux. The measured urodynamic variables
      included: maximum flow rate (Qmax), PVR, cystometric bladder capacity (CBC), detrusor
      pressure at Qmax (Pdet) and voiding efficiency (VE). The procedure and definition of
      videourodynamic study were in accordance of the recommendations of the International
      Continence Society.
    

Intervention name(s): BoNT-A (10 injection); BoNT-A (20 injection); BoNT-A (40 injection)
Intervention type(s): Drug; Drug; Drug
Intervention description(s): BoNT-A 100 U 10 injections; BoNT-A 100 U 20 injections; BoNT-A 100 U 40 injections
Other intervention name(s): Botulinum Toxin A (Botox); Botulinum Toxin A (Botox); Botulinum Toxin A (Botox)
Intervention MeSH terms: Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA; incobotulinumtoxinA
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Patients were randomized to receive different injection number of onabotulinumtoxinA
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: botulinum toxin; detrusor overactivity