Effect of 50 and 100 IU Doses of Botox A Toxin Injection in BPH Patients.
Effect of 50 and 100 IU Doses of Botox A Toxin Injection in BPH Patients.
The primary objective of this study is to compare the efficacy and safety of a single
 injection of 50 U and 100 U doses of BoNT-A for the treatment of BPH-associated LUTS.
Patients and method:

 Men with symptomatic BPH will be invited to participate in this prospective study. Inclusion
 criteria will be an age of above 50 years, persistent moderate to severe LUTS as determined
 by International Prostatic Symptom Score (IPSS) >8, peak urinary flow rate of less than 12
 mL/s, and an enlarged prostate gland on digital rectal examination. Exclusion criteria will
 be history of previous surgery for BPH, presence of urethral stenosis, urinary tract
 infection, prostate or bladder cancer, history of pelvic surgery or radiotherapy,
 neurological diseases, urinary retention and BPH-associated complications requiring surgical
 treatment including bladder stone, and bilateral hydronephrosis.

 Subjects will undergo further evaluation before treatment, including urine analysis, serum
 creatinine, prostate-specific antigen (PSA), Trans rectal prostatic and Trans abdominal
 urinary tract sonography, uroflowmetry, and measurement of post-void residual volume (PVR)
 via abdominal ultrasonography.

 Just before the injection procedure, patients will be randomized to receive either 50 U or
 100 U of BoNT-A.

 -  Intervention All patients submitted for intervention will receive oral antibiotics (oral
 levofloxacin and flagyl 500 mg) 2 days before injection. Patients will be instructed to
 avoid taking anticoagulants, such as aspirin, for at least seven days prior to the
 procedure. An enema will be done two to four hours before the ultrasound to clean out
 the bowel.

 Injection procedure: With the patient lying in lateral position, local anesthesia is
 performed with 20 mL of lidocaine 2% solution injected transrectally via transrectal
 ultrasound then wait for 10-minutes. The two different BoNT-A doses (50 U or 100 U) will be
 reconstituted with saline 0.9% to a total volume of 5 ml. All patients will receive five
 injections of 1 mL of the BoNT-A solution, including two injections in each lateral lobe (one
 proximal and one distal) and one injection in the median lobe. The injection depth will be
 7-10 mm. After the procedure, patients will remain under observation until they are able to
 void spontaneously without hematuria. Oral levofloxacin (500 mg once a day) will be
 administered for five days.

 Follow up:

 Evaluation will be performed one week, 3 and 6 months after treatment. They will include a
 clinical assessment of LUTS with the IPSS score as well as measurement of peak urinary flow
 rate and post void residual volume. Serum PSA level and prostate volume will be assessed at
 the 6th month. The primary endpoint is improvement of IPSS scores (at least 30% improvement
 from baseline to 3 months IPSS and/or maximum urinary flow rate) and safety. The study will
 be stopped if 1) a life threatening, disabling or fatal event related to the BONT-A injection
 occurred, or 2) 40% or more of the participants report a moderate or severe side effect
 related to the botulinum toxin injection.

 After 3 months, patients showing no improvement within 50 u group will be reinjected another
 dose of 100 u and then reevaluated after 3 months of reinjection.

 Statistical Analysis:

 Data will be expressed as means with standard deviations (SD) and range or absolute values
 and fractions. Intergroup changes from baseline of continuous variables will be analyzed with
 analysis of variance for repeated measurements. Intragroup comparisons will be performed
 using the Student's paired t-test. Fisher's test is used for categorical variables. A sample
 size of 17 in each group has 80% power to detect a difference between means of 3.00 (units in
 the IPSS score), at a two-tailed significance level of 0.05 or less.
Inclusion Criteria:

 -  persistent moderate to severe LUTS as determined by International Prostatic Symptom
 Score (IPSS) >8.

 -  peak urinary flow rate of less than 12 mL/s.

 -  an enlarged prostate gland on digital rectal examination.

 Exclusion Criteria:

 -  history of previous surgery for BPH.

 -  presence of urethral stenosis.

 -  urinary tract infection.

 -  prostate or bladder cancer.

 -  history of pelvic surgery or radiotherapy.

 -  neurological diseases.

 -  urinary retention.

 -  BPH-associated complications requiring surgical treatment including bladder stone, and
 bilateral hydronephrosis.