Different Injection Number of the Same Dose of Botulinum Toxin A on Overactive Bladder Syndrome
Different Injection Number of the Same Dose of Botulinum Toxin A on Overactive Bladder Syndrome
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.
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.
Inclusion Criteria:

 -  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.

 Exclusion Criteria:

 -  Use of antimuscarinic agent and effective in treatment of lower urinary tract symptoms

 -  Patients with severe cardiopulmonary disease and such as congestive heart failure,
 arrhythmia, poorly controlled hypertension, not able to receive regular follow-up

 -  Patients with bladder outlet obstruction on enrollment

 -  Patients with postvoid residual > 150ml

 -  Patients with uncontrolled confirmed diagnosis of acute urinary tract infection

 -  Patients have laboratory abnormalities at screening including:

 -  Alanine aminotransferase (ALT)> 3 x upper limit of normal range

 -  Aspartate aminotransferase (AST)> 3 x upper limit of normal range

 -  Patients have abnormal serum creatinine level > 2 x upper limit of normal range

 -  Patients with any contraindication to be urethral catheterization during treatment

 -  Female patients who is pregnant, lactating, or with child-bearing potential without
 contraception.

 -  Myasthenia gravis, Eaton Lambert syndrome.

 -  Patients with any other serious disease considered by the investigator not suitable
 for general anesthesia or in the condition to enter the trial Patients participated
 investigational drug trial within 1 month before entering this study