<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/NCT04408352</url>
  </required_header>
  <id_info>
    <org_study_id>1360-001</org_study_id>
    <nct_id>NCT04408352</nct_id>
  </id_info>
  <brief_title>RF Ablation of the Trigone for the Treatment of UUI</brief_title>
  <acronym>TRANSFORM</acronym>
  <official_title>Selective Bladder Denervation Using RF Energy for the Treatment of UUI</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hologic, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>NAMSA</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Hologic, Inc.</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_unapproved_device>Yes</is_unapproved_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this pivotal study is to collect data on the safety and&#xD;
      effectiveness of the Hologic trigone RF ablation device to reduce urgency urinary&#xD;
      incontinence. Up to 325 subjects will be enrolled with 225 randomized (2:1) and treated at up&#xD;
      to 35 sites in the U.S. Additional sites in Canada, Australia, Europe, and other countries&#xD;
      may also be considered. Sites outside of the U.S. cannot randomize more than 25% of subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Up to 325 subjects who meet all inclusion and none of the exclusion criteria will be enrolled&#xD;
      and up to 225 subjects will be randomized. Subjects will be randomized to either an active&#xD;
      arm that includes treatment with the Hologic trigone RF ablation device, or a control arm who&#xD;
      receive a sham procedure. With a 2:1 randomization, approximately 150 subjects will be&#xD;
      treated with the Hologic trigone RF ablation device (treatment group) and 75 sham subjects&#xD;
      treated with the sham procedure.&#xD;
&#xD;
      Subjects will be blinded to their randomized treatment; however, due to the nature of the&#xD;
      procedure, the treating investigator cannot be blinded to individual randomization&#xD;
      assignments.&#xD;
&#xD;
      Subjects who are randomized to the treatment arm will be followed at 2 weeks, 1 month, 3, 6,&#xD;
      and 12 months and every 6 months thereafter. Subjects randomized to the sham arm will be&#xD;
      followed through the 6-month visit. Follow up of all other subjects (cross-over and treatment&#xD;
      arm) will conclude when the last subject in randomized treatment arm reaches their 12-month&#xD;
      visit, is withdrawn, or is determined lost to follow-up.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Suspended</overall_status>
  <why_stopped>
    for business planning purposes only, and is not related to any safety or performance issues&#xD;
    identified during the study&#xD;
  </why_stopped>
  <start_date type="Actual">April 27, 2020</start_date>
  <completion_date type="Anticipated">May 2030</completion_date>
  <primary_completion_date type="Anticipated">February 2030</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>Crossover Assignment</intervention_model>
    <intervention_model_description>Subjects will be randomized to either the treatment with the Hologic trigone RF ablation device or a sham procedure. Randomization will occur in a 2:1 fashion (treatment: sham) meaning approximately 150 subjects will be treated with the Hologic trigone RF ablation device and 75 control subjects treated with the sham procedure. Randomization will be stratified by site.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
    <masking_description>The device shall be assembled and maintained in a sterile environment outside the view of the subject during procedure preparation and treatment. The treating investigator, applicable nursing and site staff, and any representatives supporting the procedure should refrain from discussing the device or treatment assignment during the procedure and applicable follow-up visits. The sham procedure will mimic the Hologic trigone RF ablation device procedure to maintain subject blinding and provide the most accurate assessment of control data while minimizing risk to the subject. Energy will not be delivered to the tissue when each sham &quot;ablation&quot; is started.To be comparable to the Hologic trigone RF ablation device procedure, the simulated ablation procedure will need to be repeated as many times as necessary to cover the area of the trigone as is done in the treatment arm.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Primary Efficacy Endpoint</measure>
    <time_frame>6 months</time_frame>
    <description>The proportion of UUI responders having a &gt; 50% decrease in UUI episodes from baseline to 6-month follow-up as documented on the 3-day bladder diary.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Primary Safety Endpoint</measure>
    <time_frame>12 months</time_frame>
    <description>All adverse events from randomized treatment through the close of the 12-month follow-up visit for subjects treated with the Hologic trigone RF ablation device.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">225</enrollment>
  <condition>Urgent Urinary Incontinence</condition>
  <arm_group>
    <arm_group_label>RF Trigone Ablation Treatment Arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>A compatible standard cystoscopy lens (30°) will be inserted into the Hologic trigone RF Device. The bladder will be emptied of urine and saline infused into the bladder to allow adequate visualization and working space. Ablations at the trigone will be created using the Hologic trigone RF ablation device together with the compatible standard commercially available RF cannula and generator. It is expected that a subject would receive between 4-6 ablations to completely treat the appropriate area of the trigone. At the completion of the procedure, 200 ml of saline is instilled into the bladder to allow for assessment of voiding function prior to discharge.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RF Trigone Ablation Sham Arm</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>The sham procedure will mimic the Hologic trigone RF ablation device procedure to maintain subject blinding and provide the most accurate assessment of control data while minimizing risk to the subject.&#xD;
The bladder will be emptied of urine and saline infused into the bladder to allow adequate visualization and working space. Suction will be applied to the bladder wall and the cannulas (needles) will be introduced into the bladder wall. Energy will not be delivered to the tissue when each sham &quot;ablation&quot; is started. In order to maintain blinding of the subject, the typical sounds that Hologic trigone RF ablation device makes during actual ablation/fulguration will be replicated. The simulated ablation procedure will be repeated as many times as necessary to cover the area of the trigone. 4 to 6 sham &quot;ablations&quot; would be required. At the completion of the procedure, 200ml of saline is instilled into the bladder to allow for assessment of voiding function prior to discharge.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>selective bladder denervation using RF energy</intervention_name>
    <description>RF ablation of the trigone for the treatment of UUI</description>
    <arm_group_label>RF Trigone Ablation Sham Arm</arm_group_label>
    <arm_group_label>RF Trigone Ablation Treatment Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Non-pregnant, non-lactating female NOTE: Females who are of childbearing potential&#xD;
             must have had a negative pregnancy test &lt;7 days prior to procedure and must be using&#xD;
             medically accepted contraception or have a monogamous relationship with a partner who&#xD;
             has undergone sterilization.&#xD;
&#xD;
          2. Subject is ≥18 years of age&#xD;
&#xD;
          3. Subject has a history of idiopathic UUI for ≥ 6 months&#xD;
&#xD;
          4. Subject is willing to provide Informed Consent, is geographically stable, has the&#xD;
             cognitive ability to complete the 3-day bladder diary and comply with the required&#xD;
             diary, follow up visits and testing schedule requirements&#xD;
&#xD;
          5. Ambulatory and able to use toilet without assistance&#xD;
&#xD;
          6. Post-void residual (PVR) ≤ 150 ml&#xD;
&#xD;
          7. Intolerant of, contraindicated for, or have failed drug therapy AND should not be on&#xD;
             medications for their condition for at least 2 weeks prior&#xD;
&#xD;
          8. Predominance of urgency urinary incontinence in subjects with mixed incontinence (mix&#xD;
             of both stress and urgency incontinence) NOTE: Predominance is defined as having at&#xD;
             least 2/3rds or 67% of reported incontinence as urgency urinary incontinence on the&#xD;
             3-day bladder diary, and a higher percentage urgency urinary incontinence score as&#xD;
             compared to the SUI score on the MESA-UIQ&#xD;
&#xD;
          9. Subject has not previously received, or did receive ≤ 100 units/intravesical treatment&#xD;
             of Onabotulinum Toxin A (Botox®) for OAB and self-reports receiving benefit from Botox&#xD;
             of normal durability (3-6 months), but discontinued or wishes to discontinue due to&#xD;
             side effects, financial constraints, or required treatment regimen (e.g., treatment&#xD;
             every 6 months)&#xD;
&#xD;
         10. ≥ 4 episodes of urgency urinary incontinence (UUI) over 3-day Bladder Diary (an&#xD;
             average of 1.33 UUI episodes/day)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Planning on becoming pregnant during the 36-month study period&#xD;
&#xD;
          2. Serum creatinine or BUN &gt; twice the upper limit of normal within the last sixty days;&#xD;
             Impaired renal function as measured by glomerular filtration rate (GFR) ≤ 65&#xD;
&#xD;
          3. Current bleeding disorder or coagulopathies&#xD;
&#xD;
          4. Neurological disease affecting bladder function such as multiple sclerosis, spinal&#xD;
             cord injuries, myasthenia gravis, Charcot-Marie-Tooth disease&#xD;
&#xD;
          5. Subject has uncontrolled diabetes (HbA1C &gt;8.5) documented in the last three months&#xD;
&#xD;
          6. Subject is a chronic corticosteroid user defined as daily continuous use within the&#xD;
             last 30 days&#xD;
&#xD;
          7. Subject is critically ill or has a life expectancy &lt;3 years&#xD;
&#xD;
          8. Investigator determines that subject is not a suitable candidate for participation in&#xD;
             an investigational clinical research study&#xD;
&#xD;
          9. Post-surgical onset of de novo OAB&#xD;
&#xD;
         10. Current hydronephrosis or hydroureter&#xD;
&#xD;
         11. Patients with uninvestigated microhematuria&#xD;
&#xD;
         12. Impaired voiding dysfunction due to underactive bladder or bladder outflow obstruction&#xD;
&#xD;
         13. Current participation in any other interventional study. Participation in&#xD;
             observational studies is permitted&#xD;
&#xD;
         14. Prior or current diagnosis of polyuria or has a screening 3-day bladder diary with&#xD;
             24-hour total volume of &gt; 3000 ml&#xD;
&#xD;
         15. Urinary tract infection (UTI) that is not resolved or has not been treated with&#xD;
             antibiotics for a minimum of 3 days at the time of procedure and has not been verified&#xD;
             by a negative urinalysis&#xD;
&#xD;
         16. Subject reports having, or has a documented history of ≥ 2 urinary tract infections&#xD;
             (UTIs) in the last 6 months, or ≥3 UTIs in the last 12 months prior to enrollment&#xD;
&#xD;
         17. Documented, spontaneous, unprovoked urinary retention requiring any type of&#xD;
             catheterization within the last 6 months or retention in the past for which there was&#xD;
             no diagnosis or definitive treatment&#xD;
&#xD;
         18. Anatomical conditions that, in the opinion of the investigator, would preclude the&#xD;
             introduction and/or use of the device&#xD;
&#xD;
         19. Any prolapse at or beyond the hymen&#xD;
&#xD;
         20. Subject has been diagnosed (at any time) with bladder cancer, interstitial cystitis or&#xD;
             chronic pelvic pain syndrome&#xD;
&#xD;
         21. Ureteral dysfunction, stricture or reflux including vesicoureteral reflux or a history&#xD;
             of surgical treatment for vesicoureteral reflux&#xD;
&#xD;
         22. Any abnormality of the urinary tract including the bladder, ureters or kidneys such as&#xD;
             but not limited to: hydroureter, hydronephrosis, ureteric reflux, Hutch diverticulum,&#xD;
             ureterocele, duplex system, ectopic ureter, unilateral renal agenesis, ectopic kidney,&#xD;
             cross fused ectopia, or megaureter&#xD;
&#xD;
         23. Any invasive or surgical intervention involving the kidneys, bladder, urethra, rectum&#xD;
             or vaginal wall within the last 6 months (e.g., radiofrequency, implant, mid-urethral&#xD;
             sling)&#xD;
&#xD;
         24. Prior history of surgical mesh in the anterior vaginal compartment to treat pelvic&#xD;
             organ prolapse&#xD;
&#xD;
         25. History of complications with any transvaginal or mid-urethral implanted mesh&#xD;
&#xD;
         26. Prior abdominal, pelvic or vaginal surgery that may have modified the structure or&#xD;
             location of the bladder, ureters or urinary vasculature such as bladder&#xD;
             reconstruction, retroperitoneal dissection or cross-trigonal ureteral implantation,&#xD;
             urinary tract fistula repair&#xD;
&#xD;
         27. Current use of OAB medications within the last 2 weeks&#xD;
&#xD;
         28. OAB symptoms previously treated with a single injection of &gt;100 units of Onabotulinum&#xD;
             Toxin A (Botox®)&#xD;
&#xD;
         29. OAB symptoms previously treated with Sacral Neuromodulation (SNM) and/or PTNS&#xD;
&#xD;
         30. Previous pelvic irradiation&#xD;
&#xD;
         31. Complete or total incontinence (i.e. the continuous or total loss of urinary control)&#xD;
&#xD;
         32. Any functional incontinence (incontinence caused by a physical or mental impairment&#xD;
             that keeps a subject from reaching the bathroom in time to urinate)&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>The study will enroll adult (≥18 years of age), female subjects with urgency urinary incontinence (UUI) who are found to be intolerant of, contraindicated for, or have failed drug therapy and are not on medications for their condition.</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Cypress Medical Research Center, LLC</name>
      <address>
        <city>Wichita</city>
        <state>Kansas</state>
        <zip>67226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regional Urology, LLC</name>
      <address>
        <city>Shreveport</city>
        <state>Louisiana</state>
        <zip>71106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Magee Womens Hospital</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alleghany Health Network</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Center for Pelvic Health</name>
      <address>
        <city>Franklin</city>
        <state>Tennessee</state>
        <zip>37067</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Urology</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>May 26, 2020</study_first_submitted>
  <study_first_submitted_qc>May 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 29, 2020</study_first_posted>
  <last_update_submitted>July 28, 2022</last_update_submitted>
  <last_update_submitted_qc>July 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 1, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Urinary Incontinence</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04408352
org study id: 1360-001
nct id: NCT04408352
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: Yes
is unapproved device: Yes
The primary objective of this pivotal study is to collect data on the safety and
      effectiveness of the Hologic trigone RF ablation device to reduce urgency urinary
      incontinence. Up to 325 subjects will be enrolled with 225 randomized (2:1) and treated at up
      to 35 sites in the U.S. Additional sites in Canada, Australia, Europe, and other countries
      may also be considered. Sites outside of the U.S. cannot randomize more than 25% of subjects.
Up to 325 subjects who meet all inclusion and none of the exclusion criteria will be enrolled
      and up to 225 subjects will be randomized. Subjects will be randomized to either an active
      arm that includes treatment with the Hologic trigone RF ablation device, or a control arm who
      receive a sham procedure. With a 2:1 randomization, approximately 150 subjects will be
      treated with the Hologic trigone RF ablation device (treatment group) and 75 sham subjects
      treated with the sham procedure.

      Subjects will be blinded to their randomized treatment; however, due to the nature of the
      procedure, the treating investigator cannot be blinded to individual randomization
      assignments.

      Subjects who are randomized to the treatment arm will be followed at 2 weeks, 1 month, 3, 6,
      and 12 months and every 6 months thereafter. Subjects randomized to the sham arm will be
      followed through the 6-month visit. Follow up of all other subjects (cross-over and treatment
      arm) will conclude when the last subject in randomized treatment arm reaches their 12-month
      visit, is withdrawn, or is determined lost to follow-up.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Subjects will be randomized to either the treatment with the Hologic trigone RF ablation device or a sham procedure. Randomization will occur in a 2:1 fashion (treatment: sham) meaning approximately 150 subjects will be treated with the Hologic trigone RF ablation device and 75 control subjects treated with the sham procedure. Randomization will be stratified by site.
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
masking description: The device shall be assembled and maintained in a sterile environment outside the view of the subject during procedure preparation and treatment. The treating investigator, applicable nursing and site staff, and any representatives supporting the procedure should refrain from discussing the device or treatment assignment during the procedure and applicable follow-up visits. The sham procedure will mimic the Hologic trigone RF ablation device procedure to maintain subject blinding and provide the most accurate assessment of control data while minimizing risk to the subject. Energy will not be delivered to the tissue when each sham "ablation" is started.To be comparable to the Hologic trigone RF ablation device procedure, the simulated ablation procedure will need to be repeated as many times as necessary to cover the area of the trigone as is done in the treatment arm.
measure: Primary Efficacy Endpoint
time frame: 6 months
description: The proportion of UUI responders having a > 50% decrease in UUI episodes from baseline to 6-month follow-up as documented on the 3-day bladder diary.
measure: Primary Safety Endpoint
time frame: 12 months
description: All adverse events from randomized treatment through the close of the 12-month follow-up visit for subjects treated with the Hologic trigone RF ablation device.
arm group label: RF Trigone Ablation Treatment Arm
arm group type: Active Comparator
description: A compatible standard cystoscopy lens (30°) will be inserted into the Hologic trigone RF Device. The bladder will be emptied of urine and saline infused into the bladder to allow adequate visualization and working space. Ablations at the trigone will be created using the Hologic trigone RF ablation device together with the compatible standard commercially available RF cannula and generator. It is expected that a subject would receive between 4-6 ablations to completely treat the appropriate area of the trigone. At the completion of the procedure, 200 ml of saline is instilled into the bladder to allow for assessment of voiding function prior to discharge.
arm group label: RF Trigone Ablation Sham Arm
arm group type: Sham Comparator
description: The sham procedure will mimic the Hologic trigone RF ablation device procedure to maintain subject blinding and provide the most accurate assessment of control data while minimizing risk to the subject.
The bladder will be emptied of urine and saline infused into the bladder to allow adequate visualization and working space. Suction will be applied to the bladder wall and the cannulas (needles) will be introduced into the bladder wall. Energy will not be delivered to the tissue when each sham "ablation" is started. In order to maintain blinding of the subject, the typical sounds that Hologic trigone RF ablation device makes during actual ablation/fulguration will be replicated. The simulated ablation procedure will be repeated as many times as necessary to cover the area of the trigone. 4 to 6 sham "ablations" would be required. At the completion of the procedure, 200ml of saline is instilled into the bladder to allow for assessment of voiding function prior to discharge.
intervention type: Device
intervention name: selective bladder denervation using RF energy
description: RF ablation of the trigone for the treatment of UUI
arm group label: RF Trigone Ablation Sham Arm
arm group label: RF Trigone Ablation Treatment Arm
criteria: 
gender: Female
gender based: Yes
gender description: The study will enroll adult (≥18 years of age), female subjects with urgency urinary incontinence (UUI) who are found to be intolerant of, contraindicated for, or have failed drug therapy and are not on medications for their condition.
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Urinary Incontinence
sharing ipd: Undecided