Efficacy of Li-SWT on Persistent Storage Symptoms After Transurethral Surgery for BPO

Study Overview
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Brief Summary
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comparing the outcome of low-intensity shock wave therapy (Li-SWT) versus solifenacin on persistent storage symptoms after transurethral surgery for benign prostatic obstruction (BPO)

Detailed Description
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Benign prostatic hyperplasia (BPH) is a common cause of lower urinary tract symptoms (LUTS) in aging men including both voiding and storage symptoms. After prostatectomy, 20-30% of the patients still have persistent storage symptoms. The pathophysiology of persistent storage symptoms after surgical relief of benign prostatic obstruction (BPO) remains unclear. It may be due to bladder changes produced by long standing bladder outlet obstruction (BOO) including bladder ischemia and denervation or it may be related to other factors rather than preoperative BOO such as aging, chronic inflammation or a subtle neurological disorder. After exclusion of urinary tract infection (UTI) and BOO, antimuscarinics are the commonly used medications for post-prostatectomy persistent storage symptoms. However, these medications are associated with side effects which may interfere with the patient compliance. Low-intensity shock wave therapy (Li-SWT) is a non invasive procedure that has a beneficial effect in promoting revascularization and enhancing tissue regeneration. It has been applied to the penis for erectile dysfunction and to the perineum for chronic pelvic pain syndrome (CPPS) with encouraging results. In a rat model, it has been reported that defocused Li-SWT leads to improvement of bladder innervation and vascularization. Based on the previously mentioned studies, the investigators hypothesized that Li-SWT can offer benefit in improvement of persistent storage symptoms after surgical relief of BPO. In the present study, the investigators will evaluate the effect of Li-SWT on persistent storage symptoms after transurethral surgery for BPO compared to antimuscarinics in a randomized controlled trial (RCT).

Official Title
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Efficacy of Low-intensity Shock Wave Therapy on Persistent Storage Symptoms After Transurethral Surgery for Benign Prostatic Obstruction: A Randomized Controlled Trial

Conditions
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Overactive Bladder, Urinary Incontinence, Urge, Urgency-frequency Syndrome, Post Prostatectomy

Intervention / Treatment
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* Procedure: Li-SWT (suprapubic approach)
* Procedure: Li-SWT (perineal approach)
* Procedure: Li-SWT (combined approach)
* Procedure: Sham treatment
* Drug: Solifenacin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients have to fulfill all the following criteria to be included in the study: Ability to give informed consent and reply to questionnaires. Average urgency episodes per 24 hrs ≥ 1 and average daytime frequency ≥ 8 during the baseline 3-day voiding diary. Relief of BOO as proved by non-invasive uroflowmetry, pressure flow study (PFS) or urethrocystoscopy. Exclusion Criteria: Patients who have any of the following will be excluded from the study: Untreated UTI. BOO such as bladder neck contracture (BNC), residual obstructing adenoma or urethral stricture. Neurogenic lower urinary tract dysfunction (LUTD). Uncontrolled diabetes mellitus. Depression or any psychogenic disorders. Prior radiation therapy to the pelvic area. History of prostate cancer, bladder tumor or intravesical Bacillus Calmette Guerin (BCG) therapy. Poor coagulopathy. Severe cardiovascular disease.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Li-SWT<br>Patients will be treated by 8 sessions of Li-SWT with one week interval. This group is subdivided into 3 subgroups according to the approach through which Li-SWT is applied; suprapubic, perineal and combined approaches | Procedure: Li-SWT (suprapubic approach)<br>* The patient will be asked to lie in flat dorsal position. A commercially used gel for sonography will be applied to the suprapubic region. The applicator will be placed on suprapubic region with two fingers apart from the symphysis pubis tilting to 45°. Shock waves will be directed to 3 different sites; the midline (over the bladder dome) and 3 cm right and left to the midline (over bilateral bladder walls). The patient will receive 3000 shocks (1000 shocks per site) with energy flux density of 0.12 mJ/mm² and frequency of 4 Hz.<br>Procedure: Li-SWT (perineal approach)<br>* The patient will be asked to lie in lithotomy position. A commercially used gel for sonography will be applied to the perineum. The applicator will be placed on perineal region. Shock waves will be directed to 3 different sites: the midline and 2 cm above and below the midline. The patient will receive 3000 shocks (1000 shocks per site) with energy flux density of 0.12 mJ/mm² and frequency of 4 Hz.<br>Procedure: Li-SWT (combined approach)<br>* The patient will receive 3000 shocks; 1500 shocks through suprapubic approach (500 shocks per site) and another 1500 shocks through perineal approach (500 shocks per site) with energy flux density of 0.12 mJ/mm² and frequency of 4 Hz.<br>|
| Sham Comparator: Sham treatment<br>Patients will be treated by 8 sessions of sham treatment with one week interval, applied through suprapubic and perineal approaches. | Procedure: Sham treatment<br>* The same technique of Li-SWT will be used but the applicator of the shock wave device will be turned off.<br>|
| Active Comparator: antimuscarinics<br>Patients will be treated by solifenacin 10 mg once daily for 6 months. | Drug: Solifenacin<br>* The patients will be treated by antimuscarinics (solifenacin) which are considered as the conventional treatment of storage symptoms after prostatectomy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percent change in overactive bladder symptoms score (OABSS) | The primary endpoint is the percent change from baseline in the total score of OABSS (total score = 15) at 3-month follow up. | approximately 20 months | 
| Percent of responders | The percent of responders at 3-month follow up. Three points reduction in the total score of OABSS is determined as the minimal threshold for a meaningful change. Responders are defined as patients who achieved reduction in the total score of OABSS ≥ 3 at 3-month follow up, and those patients will continue on the same treatment modality. | approximately 20 months | 
| The numerical change in overactive bladder symptoms score (OABSS) | The numerical change from baseline in the total score and sub-scores of OABSS at 3 and 6-month follow up will be reported. | approximately 2 years. | 
| 3-day voiding diary | Change in daytime frequency (times/24hrs), urgency (times/24hrs), urge incontinence (times/24hrs), nocturia (times/24hrs) and average voided volume/micturition (ml) from baseline will be compared at 3 and 6-month follow up. | approximately 2 years. | 
| Incidence of adverse events associated with treatment | Incidence of adverse events associated with Li-SWT or solifenacin (n%) should be reported. | approximately 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| International index of prostate symptom score (IPSS) | Change in IPSS at 0, 3 and 6 months will be compared. | approximately 2 years. | 
| Post voiding residual urine (PVR) | Change in PVR (ml) at 0, 3 and 6 months will be compared. | approximately 2 years. | 
| Maximum flow rate (Qmax) | Change in Qmax (ml/s) at 0, 3 and 6 months will be compared. | approximately 2 years. | 
| International index of erectile function-15 ( IIEF-15) | Change in IIEF-15) at 0, 3 and 6 months will be compared. | approximately 2 years. | 
| Cystometric bladder capacity | Change in bladder volume (ml) at first sensation of filling and maximum cystometric capacity (ml) at 0 and 6 months will be analysed. | approximately 2 years. | 
| Detrusor overactivity | Change in detrusor stability and maximum amplitude (cmH2O) of detrusor overactivity during cystometry at 0 and 6 months will be analysed. | approximately 2 years. | 
| Detrusor contractility | Change in maximum detrusor pressure (cmH2O) and BCI during voiding at 0 and 6 months will be analysed. | approximately 2 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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low-intensity shock wave therapy, persistent storage symptoms, benign prostatic obstruction