<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04437108</url>
  </required_header>
  <id_info>
    <org_study_id>Li-SWT after relief of BPO</org_study_id>
    <nct_id>NCT04437108</nct_id>
  </id_info>
  <brief_title>Efficacy of Li-SWT on Persistent Storage Symptoms After Transurethral Surgery for BPO</brief_title>
  <official_title>Efficacy of Low-intensity Shock Wave Therapy on Persistent Storage Symptoms After Transurethral Surgery for Benign Prostatic Obstruction: A Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mansoura University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ahmed Mohamed Elshal</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Mansoura University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      comparing the outcome of low-intensity shock wave therapy (Li-SWT) versus solifenacin on&#xD;
      persistent storage symptoms after transurethral surgery for benign prostatic obstruction&#xD;
      (BPO)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Benign prostatic hyperplasia (BPH) is a common cause of lower urinary tract symptoms (LUTS)&#xD;
      in aging men including both voiding and storage symptoms. After prostatectomy, 20-30% of the&#xD;
      patients still have persistent storage symptoms. The pathophysiology of persistent storage&#xD;
      symptoms after surgical relief of benign prostatic obstruction (BPO) remains unclear. It may&#xD;
      be due to bladder changes produced by long standing bladder outlet obstruction (BOO)&#xD;
      including bladder ischemia and denervation or it may be related to other factors rather than&#xD;
      preoperative BOO such as aging, chronic inflammation or a subtle neurological disorder.&#xD;
&#xD;
      After exclusion of urinary tract infection (UTI) and BOO, antimuscarinics are the commonly&#xD;
      used medications for post-prostatectomy persistent storage symptoms. However, these&#xD;
      medications are associated with side effects which may interfere with the patient compliance.&#xD;
&#xD;
      Low-intensity shock wave therapy (Li-SWT) is a non invasive procedure that has a beneficial&#xD;
      effect in promoting revascularization and enhancing tissue regeneration. It has been applied&#xD;
      to the penis for erectile dysfunction and to the perineum for chronic pelvic pain syndrome&#xD;
      (CPPS) with encouraging results. In a rat model, it has been reported that defocused Li-SWT&#xD;
      leads to improvement of bladder innervation and vascularization.&#xD;
&#xD;
      Based on the previously mentioned studies, the investigators hypothesized that Li-SWT can&#xD;
      offer benefit in improvement of persistent storage symptoms after surgical relief of BPO. In&#xD;
      the present study, the investigators will evaluate the effect of Li-SWT on persistent storage&#xD;
      symptoms after transurethral surgery for BPO compared to antimuscarinics in a randomized&#xD;
      controlled trial (RCT).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 4, 2020</start_date>
  <completion_date type="Actual">July 21, 2022</completion_date>
  <primary_completion_date type="Actual">April 12, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The percent change in overactive bladder symptoms score (OABSS)</measure>
    <time_frame>approximately 20 months</time_frame>
    <description>The primary endpoint is the percent change from baseline in the total score of OABSS (total score = 15) at 3-month follow up.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percent of responders</measure>
    <time_frame>approximately 20 months</time_frame>
    <description>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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The numerical change in overactive bladder symptoms score (OABSS)</measure>
    <time_frame>approximately 2 years.</time_frame>
    <description>The numerical change from baseline in the total score and sub-scores of OABSS at 3 and 6-month follow up will be reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>3-day voiding diary</measure>
    <time_frame>approximately 2 years.</time_frame>
    <description>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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of adverse events associated with treatment</measure>
    <time_frame>approximately 18 months</time_frame>
    <description>Incidence of adverse events associated with Li-SWT or solifenacin (n%) should be reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>International index of prostate symptom score (IPSS)</measure>
    <time_frame>approximately 2 years.</time_frame>
    <description>Change in IPSS at 0, 3 and 6 months will be compared.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post voiding residual urine (PVR)</measure>
    <time_frame>approximately 2 years.</time_frame>
    <description>Change in PVR (ml) at 0, 3 and 6 months will be compared.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum flow rate (Qmax)</measure>
    <time_frame>approximately 2 years.</time_frame>
    <description>Change in Qmax (ml/s) at 0, 3 and 6 months will be compared.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>International index of erectile function-15 ( IIEF-15)</measure>
    <time_frame>approximately 2 years.</time_frame>
    <description>Change in IIEF-15) at 0, 3 and 6 months will be compared.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cystometric bladder capacity</measure>
    <time_frame>approximately 2 years.</time_frame>
    <description>Change in bladder volume (ml) at first sensation of filling and maximum cystometric capacity (ml) at 0 and 6 months will be analysed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Detrusor overactivity</measure>
    <time_frame>approximately 2 years.</time_frame>
    <description>Change in detrusor stability and maximum amplitude (cmH2O) of detrusor overactivity during cystometry at 0 and 6 months will be analysed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Detrusor contractility</measure>
    <time_frame>approximately 2 years.</time_frame>
    <description>Change in maximum detrusor pressure (cmH2O) and BCI during voiding at 0 and 6 months will be analysed.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">132</enrollment>
  <condition>Overactive Bladder</condition>
  <condition>Urinary Incontinence, Urge</condition>
  <condition>Urgency-frequency Syndrome</condition>
  <condition>Post Prostatectomy</condition>
  <arm_group>
    <arm_group_label>Li-SWT</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham treatment</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Patients will be treated by 8 sessions of sham treatment with one week interval, applied through suprapubic and perineal approaches.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>antimuscarinics</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will be treated by solifenacin 10 mg once daily for 6 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Li-SWT (suprapubic approach)</intervention_name>
    <description>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.</description>
    <arm_group_label>Li-SWT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Li-SWT (perineal approach)</intervention_name>
    <description>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.</description>
    <arm_group_label>Li-SWT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Li-SWT (combined approach)</intervention_name>
    <description>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.</description>
    <arm_group_label>Li-SWT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Sham treatment</intervention_name>
    <description>The same technique of Li-SWT will be used but the applicator of the shock wave device will be turned off.</description>
    <arm_group_label>Sham treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Solifenacin</intervention_name>
    <description>The patients will be treated by antimuscarinics (solifenacin) which are considered as the conventional treatment of storage symptoms after prostatectomy.</description>
    <arm_group_label>antimuscarinics</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients have to fulfill all the following criteria to be included in the study:&#xD;
&#xD;
               1. Ability to give informed consent and reply to questionnaires.&#xD;
&#xD;
               2. Average urgency episodes per 24 hrs ≥ 1 and average daytime frequency ≥ 8 during&#xD;
                  the baseline 3-day voiding diary.&#xD;
&#xD;
               3. Relief of BOO as proved by non-invasive uroflowmetry, pressure flow study (PFS)&#xD;
                  or urethrocystoscopy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have any of the following will be excluded from the study:&#xD;
&#xD;
               1. Untreated UTI.&#xD;
&#xD;
               2. BOO such as bladder neck contracture (BNC), residual obstructing adenoma or&#xD;
                  urethral stricture.&#xD;
&#xD;
               3. Neurogenic lower urinary tract dysfunction (LUTD).&#xD;
&#xD;
               4. Uncontrolled diabetes mellitus.&#xD;
&#xD;
               5. Depression or any psychogenic disorders.&#xD;
&#xD;
               6. Prior radiation therapy to the pelvic area.&#xD;
&#xD;
               7. History of prostate cancer, bladder tumor or intravesical Bacillus Calmette&#xD;
                  Guerin (BCG) therapy.&#xD;
&#xD;
               8. Poor coagulopathy.&#xD;
&#xD;
               9. Severe cardiovascular disease.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Patients suffering from persistent storage symptoms ≥ 3 months following any transurethral surgery for BPO will be asked to participate in this study.</gender_description>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mohammed Hegazy</last_name>
    <role>Principal Investigator</role>
    <affiliation>Urology and nephrology center, Mansoura, Egypt</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mohamed Gaballah</last_name>
    <role>Study Director</role>
    <affiliation>Urology and nephrology center, Mansoura, Egypt</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Khaled Sheir</last_name>
    <role>Study Director</role>
    <affiliation>Urology and nephrology center, Mansoura, Egypt</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ahmed Elshal</last_name>
    <role>Study Director</role>
    <affiliation>Urology and nephrology center, Mansoura, Egypt</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Urology and Nephrology center</name>
      <address>
        <city>Mansoura</city>
        <zip>35516</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>June 11, 2020</study_first_submitted>
  <study_first_submitted_qc>June 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 18, 2020</study_first_posted>
  <last_update_submitted>June 12, 2023</last_update_submitted>
  <last_update_submitted_qc>June 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mansoura University</investigator_affiliation>
    <investigator_full_name>Mohammed Hegazy</investigator_full_name>
    <investigator_title>assistant lecturer of urology</investigator_title>
  </responsible_party>
  <keyword>low-intensity shock wave therapy</keyword>
  <keyword>persistent storage symptoms</keyword>
  <keyword>benign prostatic obstruction</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Urinary Incontinence</mesh_term>
    <mesh_term>Urinary Bladder, Overactive</mesh_term>
    <mesh_term>Urinary Incontinence, Urge</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Solifenacin Succinate</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04437108
org study id: Li-SWT after relief of BPO
nct id: NCT04437108
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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)
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).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The percent change in overactive bladder symptoms score (OABSS)
time frame: approximately 20 months
description: The primary endpoint is the percent change from baseline in the total score of OABSS (total score = 15) at 3-month follow up.
measure: Percent of responders
time frame: approximately 20 months
description: 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.
measure: The numerical change in overactive bladder symptoms score (OABSS)
time frame: approximately 2 years.
description: The numerical change from baseline in the total score and sub-scores of OABSS at 3 and 6-month follow up will be reported.
measure: 3-day voiding diary
time frame: approximately 2 years.
description: 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.
measure: Incidence of adverse events associated with treatment
time frame: approximately 18 months
description: Incidence of adverse events associated with Li-SWT or solifenacin (n%) should be reported.
measure: International index of prostate symptom score (IPSS)
time frame: approximately 2 years.
description: Change in IPSS at 0, 3 and 6 months will be compared.
measure: Post voiding residual urine (PVR)
time frame: approximately 2 years.
description: Change in PVR (ml) at 0, 3 and 6 months will be compared.
measure: Maximum flow rate (Qmax)
time frame: approximately 2 years.
description: Change in Qmax (ml/s) at 0, 3 and 6 months will be compared.
measure: International index of erectile function-15 ( IIEF-15)
time frame: approximately 2 years.
description: Change in IIEF-15) at 0, 3 and 6 months will be compared.
measure: Cystometric bladder capacity
time frame: approximately 2 years.
description: Change in bladder volume (ml) at first sensation of filling and maximum cystometric capacity (ml) at 0 and 6 months will be analysed.
measure: Detrusor overactivity
time frame: approximately 2 years.
description: Change in detrusor stability and maximum amplitude (cmH2O) of detrusor overactivity during cystometry at 0 and 6 months will be analysed.
measure: Detrusor contractility
time frame: approximately 2 years.
description: Change in maximum detrusor pressure (cmH2O) and BCI during voiding at 0 and 6 months will be analysed.
arm group label: Li-SWT
arm group type: Active Comparator
description: 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
arm group label: Sham treatment
arm group type: Sham Comparator
description: Patients will be treated by 8 sessions of sham treatment with one week interval, applied through suprapubic and perineal approaches.
arm group label: antimuscarinics
arm group type: Active Comparator
description: Patients will be treated by solifenacin 10 mg once daily for 6 months.
intervention type: Procedure
intervention name: Li-SWT (suprapubic approach)
description: 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.
arm group label: Li-SWT
intervention type: Procedure
intervention name: Li-SWT (perineal approach)
description: 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.
arm group label: Li-SWT
intervention type: Procedure
intervention name: Li-SWT (combined approach)
description: 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.
arm group label: Li-SWT
intervention type: Procedure
intervention name: Sham treatment
description: The same technique of Li-SWT will be used but the applicator of the shock wave device will be turned off.
arm group label: Sham treatment
intervention type: Drug
intervention name: Solifenacin
description: The patients will be treated by antimuscarinics (solifenacin) which are considered as the conventional treatment of storage symptoms after prostatectomy.
arm group label: antimuscarinics
criteria: 
gender: Male
gender based: Yes
gender description: Patients suffering from persistent storage symptoms ≥ 3 months following any transurethral surgery for BPO will be asked to participate in this study.
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Mohammed Hegazy
role: Principal Investigator
affiliation: Urology and nephrology center, Mansoura, Egypt
last name: Mohamed Gaballah
role: Study Director
affiliation: Urology and nephrology center, Mansoura, Egypt
last name: Khaled Sheir
role: Study Director
affiliation: Urology and nephrology center, Mansoura, Egypt
last name: Ahmed Elshal
role: Study Director
affiliation: Urology and nephrology center, Mansoura, Egypt
facility: 
country: Egypt
responsible party type: Principal Investigator
investigator affiliation: Mansoura University
investigator full name: Mohammed Hegazy
investigator title: assistant lecturer of urology
mesh term: Urinary Incontinence
mesh term: Urinary Bladder, Overactive
mesh term: Urinary Incontinence, Urge
mesh term: Solifenacin Succinate