<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/NCT02262936</url>
  </required_header>
  <id_info>
    <org_study_id>14-0188-A</org_study_id>
    <secondary_id>14-56</secondary_id>
    <secondary_id>14-16</secondary_id>
    <nct_id>NCT02262936</nct_id>
  </id_info>
  <brief_title>Comparison Between Desmopressin and Fesoterodine for Treatment of Night Time Voiding in Women Aged 65 and Older</brief_title>
  <acronym>DEFEND</acronym>
  <official_title>A Randomized Double-blinded Trial Comparing DEsmopressin to FEsoterodine in the Treatment of Severe Nocturia in Women Aged 65 and olDer: The DEFEND Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mount Sinai Hospital, Canada</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Baycrest</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Physicians' Services Incorporated Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Mount Sinai Hospital, Canada</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Nocturia, or voiding at night, is an extremely troublesome symptom which is highly prevalent&#xD;
      in the elderly. Desmopressin is a treatment for nocturia but it can result in hyponatremia&#xD;
      (low blood sodium), particularly in those aged 65 and older. Fesoterodine is used for the&#xD;
      treatment of overactive bladder (OAB). Recent trials showed Fesoterodine was effective in&#xD;
      reducing nocturia. This study aims to answer the following: In women 65 and older with severe&#xD;
      nocturia, is Fesoterodine more effective than Desmopressin in reducing the number of night&#xD;
      time voids? Does Fesoterodine have a better side effect profile compared to Desmopressin?&#xD;
&#xD;
      The study design is a 12 week randomized double-blinded trial of Fesoterodine and&#xD;
      Desmopressin in the treatment of severe nocturia in women aged 65 and older. This will be&#xD;
      conducted at the Urogynecology Unit at Mount Sinai Hospital (MSH) and Baycrest. A 3 day&#xD;
      voiding diary and Nocturia, Nocturnal Enuresis and Sleep-interruption Questionnaire (NNES-Q)&#xD;
      will be completed at baseline and at week 12. The primary outcome will be the number of night&#xD;
      time voids in the Fesoterodine group compared to the Desmopressin group, 12 weeks after&#xD;
      starting treatment. Secondary outcomes include changes in the NNES-Q scores and the safety of&#xD;
      each medication.&#xD;
&#xD;
      This study is expected to show that, in women 65 and older with severe nocturia, Fesoterodine&#xD;
      will be more effective in reducing the number of night time voids, reducing the volume of&#xD;
      voided urine, increasing the duration of sleep prior to first nocturnal void and improving&#xD;
      quality of life relative to Desmopressin. Fesoterodine will also be better tolerated, with&#xD;
      fewer significant adverse events, relative to Desmopressin.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will include female patients 65 years and older from the Urogynecology Units at&#xD;
      Mount Sinai Hospital (MSH) and Baycrest. It will be a 12 week prospective, randomized&#xD;
      double-blind trial comparing treatment of nocturia using Fesoterodine and Desmopressin.&#xD;
      Patients who agree to participate in the study will receive a starting dose of either&#xD;
      Fesoterodine 4mg tablet at bedtime or Desmopressin 0.1mg tablet at bedtime. After 4 weeks, if&#xD;
      patients have had minimal improvement in their symptoms and are not significantly affected by&#xD;
      side effects, patients will have the option of increasing the dose of their medication to 8mg&#xD;
      of Fesoterodine or 0.2mg of Desmopressin. This decision will be made by the patient and&#xD;
      physician together.&#xD;
&#xD;
      Patients will undergo block randomization by pharmacy. All patients and investigators will be&#xD;
      blinded to the treatment group. Patients will be followed for 12 weeks, with visits at 4 and&#xD;
      12 weeks. Patients will also have urine cultures and uroflowmetry with measurement of&#xD;
      post-void residuals at these visits, as per clinic standard of care. Venipuncture to monitor&#xD;
      electrolyte levels will be done at baseline, 1 week after randomization and then monthly&#xD;
      until the end of the study. If patients choose to increase their dose at the 4 week visit,&#xD;
      electrolyte levels will be repeated one week after the dose adjustment and then monthly until&#xD;
      the end of the study. The last follow up is at 12 weeks, when a 3 day voiding diary and the&#xD;
      NNES-Q will be collected.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Poor recruitment&#xD;
  </why_stopped>
  <start_date>July 2015</start_date>
  <completion_date type="Actual">February 2016</completion_date>
  <primary_completion_date type="Actual">February 2016</primary_completion_date>
  <phase>Phase 2/Phase 3</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of night time voids</measure>
    <time_frame>18 months</time_frame>
    <description>Patients will complete a 3-day voiding diary at baseline and after 12 weeks of treatment. The number of night time voids will be compared before and after treatment. The anticipated reduction in night time voids between the two treatment groups will be compared.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse event profile</measure>
    <time_frame>18 months</time_frame>
    <description>Type and number of adverse events will be collected and compared between the two treatment groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life</measure>
    <time_frame>18 months</time_frame>
    <description>Quality of life, as measured by the Nocturia, Nocturnal Enuresis and Sleep-interruptions Questionnaire (NNES-Q) will be compared between the two treatment groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Nocturnal voided volume</measure>
    <time_frame>18 months</time_frame>
    <description>The total volume of urine voided at night will be compared between the two treatment groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to first nocturnal void</measure>
    <time_frame>18 months</time_frame>
    <description>The number of minutes of sleep prior to first waking at night to void will be compared between the two treatment groups.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">4</enrollment>
  <condition>Nocturia</condition>
  <arm_group>
    <arm_group_label>Desmopressin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients randomized to receive Desmopressin will be given 0.1mg daily by mouth at bedtime. After 4 weeks, patients will have the option to increase their dose to 0.2mg daily by mouth at bedtime. Total time of drug administration will be 12 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fesoterodine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients randomized to receive Fesoterodine will be given 4mg daily by mouth at bedtime. After 4 weeks, patients will have the option to increase their dose to 8mg daily by mouth at bedtime. Total time of drug administration will be 12 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Desmopressin</intervention_name>
    <arm_group_label>Desmopressin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fesoterodine</intervention_name>
    <arm_group_label>Fesoterodine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Menopausal female patients aged 65 years and older&#xD;
&#xD;
          -  Patients with severe nocturia, defined as waking to void 3 or more times at night due&#xD;
             to an urge to void&#xD;
&#xD;
          -  Patients capable of understanding and having signed the consent form after full&#xD;
             discussion of the research, nature of the treatment, its risks and benefits&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Urinary tract infection or chronic inflammation such as interstitial cystitis and&#xD;
             bladder stones&#xD;
&#xD;
          -  Urinary and gastric retention&#xD;
&#xD;
          -  Narrow-angle glaucoma&#xD;
&#xD;
          -  von Willebrand's disease&#xD;
&#xD;
          -  Chronic severe constipation or history of gastrointestinal obstructive disease&#xD;
&#xD;
          -  Untreated congestive heart failure and venous insufficiency&#xD;
&#xD;
          -  Untreated hypertension or tachycardia&#xD;
&#xD;
          -  Untreated renal or liver disease&#xD;
&#xD;
          -  Untreated diabetes mellitus or insipidus&#xD;
&#xD;
          -  Unexplained and untreated electrolyte disturbances&#xD;
&#xD;
          -  Any clinical condition which in the opinion of the investigator would not allow safe&#xD;
             completion of the study&#xD;
&#xD;
          -  Current use of diuretics with untreated electrolyte disturbances&#xD;
&#xD;
          -  Patients taking drugs known to be strong CYP3A4 inhibitors (protease inhibitors,&#xD;
             ketoconazole, clarithromycin) or strong CYP3A4 inducers (carbamazepine, phenytoin, St.&#xD;
             John's Wort) used on a regular basis&#xD;
&#xD;
          -  Patients taking anticholinergic or antispasmodic medications who did not comply with a&#xD;
             minimum 14 days washout period&#xD;
&#xD;
          -  Previous failed therapy with Fesoterodine or Desmopressin&#xD;
&#xD;
          -  Hypersensitivity or intolerance to Fesoterodine or Desmopressin&#xD;
&#xD;
          -  Hypersensitivity to soya, peanuts or lactose&#xD;
&#xD;
          -  Clinically significant outlet obstruction as determined by the investigator&#xD;
&#xD;
          -  Patients with Post Void Residual (PVR) &gt; 100 ml&#xD;
&#xD;
          -  Patients with Mini-Mental State Exam (MMSE) &lt;24&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Harold P Drutz, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>MOUNT SINAI HOSPITAL</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mount Sinai Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G1X5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>October 8, 2014</study_first_submitted>
  <study_first_submitted_qc>October 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 13, 2014</study_first_posted>
  <last_update_submitted>November 11, 2016</last_update_submitted>
  <last_update_submitted_qc>November 11, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 15, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Aged</keyword>
  <keyword>Deamino Arginine Vasopressin</keyword>
  <keyword>Fesoterodine</keyword>
  <keyword>Randomized Controlled Trial</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nocturia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Deamino Arginine Vasopressin</mesh_term>
    <mesh_term>Fesoterodine</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/NCT02262936
org study id: 14-0188-A
secondary id: 14-56
secondary id: 14-16
nct id: NCT02262936
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
Nocturia, or voiding at night, is an extremely troublesome symptom which is highly prevalent
      in the elderly. Desmopressin is a treatment for nocturia but it can result in hyponatremia
      (low blood sodium), particularly in those aged 65 and older. Fesoterodine is used for the
      treatment of overactive bladder (OAB). Recent trials showed Fesoterodine was effective in
      reducing nocturia. This study aims to answer the following: In women 65 and older with severe
      nocturia, is Fesoterodine more effective than Desmopressin in reducing the number of night
      time voids? Does Fesoterodine have a better side effect profile compared to Desmopressin?

      The study design is a 12 week randomized double-blinded trial of Fesoterodine and
      Desmopressin in the treatment of severe nocturia in women aged 65 and older. This will be
      conducted at the Urogynecology Unit at Mount Sinai Hospital (MSH) and Baycrest. A 3 day
      voiding diary and Nocturia, Nocturnal Enuresis and Sleep-interruption Questionnaire (NNES-Q)
      will be completed at baseline and at week 12. The primary outcome will be the number of night
      time voids in the Fesoterodine group compared to the Desmopressin group, 12 weeks after
      starting treatment. Secondary outcomes include changes in the NNES-Q scores and the safety of
      each medication.

      This study is expected to show that, in women 65 and older with severe nocturia, Fesoterodine
      will be more effective in reducing the number of night time voids, reducing the volume of
      voided urine, increasing the duration of sleep prior to first nocturnal void and improving
      quality of life relative to Desmopressin. Fesoterodine will also be better tolerated, with
      fewer significant adverse events, relative to Desmopressin.
This study will include female patients 65 years and older from the Urogynecology Units at
      Mount Sinai Hospital (MSH) and Baycrest. It will be a 12 week prospective, randomized
      double-blind trial comparing treatment of nocturia using Fesoterodine and Desmopressin.
      Patients who agree to participate in the study will receive a starting dose of either
      Fesoterodine 4mg tablet at bedtime or Desmopressin 0.1mg tablet at bedtime. After 4 weeks, if
      patients have had minimal improvement in their symptoms and are not significantly affected by
      side effects, patients will have the option of increasing the dose of their medication to 8mg
      of Fesoterodine or 0.2mg of Desmopressin. This decision will be made by the patient and
      physician together.

      Patients will undergo block randomization by pharmacy. All patients and investigators will be
      blinded to the treatment group. Patients will be followed for 12 weeks, with visits at 4 and
      12 weeks. Patients will also have urine cultures and uroflowmetry with measurement of
      post-void residuals at these visits, as per clinic standard of care. Venipuncture to monitor
      electrolyte levels will be done at baseline, 1 week after randomization and then monthly
      until the end of the study. If patients choose to increase their dose at the 4 week visit,
      electrolyte levels will be repeated one week after the dose adjustment and then monthly until
      the end of the study. The last follow up is at 12 weeks, when a 3 day voiding diary and the
      NNES-Q will be collected.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of night time voids
time frame: 18 months
description: Patients will complete a 3-day voiding diary at baseline and after 12 weeks of treatment. The number of night time voids will be compared before and after treatment. The anticipated reduction in night time voids between the two treatment groups will be compared.
measure: Adverse event profile
time frame: 18 months
description: Type and number of adverse events will be collected and compared between the two treatment groups.
measure: Quality of life
time frame: 18 months
description: Quality of life, as measured by the Nocturia, Nocturnal Enuresis and Sleep-interruptions Questionnaire (NNES-Q) will be compared between the two treatment groups.
measure: Nocturnal voided volume
time frame: 18 months
description: The total volume of urine voided at night will be compared between the two treatment groups.
measure: Time to first nocturnal void
time frame: 18 months
description: The number of minutes of sleep prior to first waking at night to void will be compared between the two treatment groups.
arm group label: Desmopressin
arm group type: Active Comparator
description: Patients randomized to receive Desmopressin will be given 0.1mg daily by mouth at bedtime. After 4 weeks, patients will have the option to increase their dose to 0.2mg daily by mouth at bedtime. Total time of drug administration will be 12 weeks.
arm group label: Fesoterodine
arm group type: Active Comparator
description: Patients randomized to receive Fesoterodine will be given 4mg daily by mouth at bedtime. After 4 weeks, patients will have the option to increase their dose to 8mg daily by mouth at bedtime. Total time of drug administration will be 12 weeks.
intervention type: Drug
intervention name: Desmopressin
arm group label: Desmopressin
intervention type: Drug
intervention name: Fesoterodine
arm group label: Fesoterodine
criteria: 
gender: Female
minimum age: 65 Years
maximum age: N/A
healthy volunteers: No
last name: Harold P Drutz, MD
role: Principal Investigator
affiliation: MOUNT SINAI HOSPITAL
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Nocturia
mesh term: Deamino Arginine Vasopressin
mesh term: Fesoterodine