<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/NCT03038321</url>
  </required_header>
  <id_info>
    <org_study_id>R/17.01.02</org_study_id>
    <nct_id>NCT03038321</nct_id>
  </id_info>
  <brief_title>Solifenacin, Levofloxacin or Lornoxicam, Which Is Ideal for Management of Intravesical Instillation BCG Side Effects?</brief_title>
  <official_title>Solifenacin vs Levofloxacin vs Lornoxicam for Management of Intravesical Instillation of Bacillus Calmette-Guerin (BCG) Side Effects A Single Blinded Randomised Controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mansoura University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Compare the different supposed clinical treatment of side effects associated with&#xD;
      intravesical BCG by levofloxacin (quinolones) vs solifenacin (selective anti-muscarinic) vs&#xD;
      lornoxicam (NSAID)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      For urothelial carcinoma (UC), which accounts for over 90% of bladder cancers, more than 70%&#xD;
      of bladder cancer patients present with non-muscle-invasive disease. Approximately 40-80% of&#xD;
      these tumors will recur within the first year, of which 10-25% will progress to&#xD;
      muscle-invasive disease.&#xD;
&#xD;
      Intravesical treatments with cytotoxic chemotherapy and immunotherapy have become the&#xD;
      mainstay following transurethral resection (TUR). Increasing knowledge of BCG use allows for&#xD;
      effective management of these once debilitating side effects. The majority of patients will&#xD;
      still experience cystitis-like symptoms to some degree, including urinary frequency (71%),&#xD;
      cystitis (67%), fever (25%), and hematuria (23%).&#xD;
&#xD;
      Oxybutynin increases in fever, flu-like symptoms, dry mouth and constipation. However, in&#xD;
      this study oxybutynin started the night before treatment causing an element of incomplete&#xD;
      bladder emptying and allowing an increased BCG dwell time. We think that these effect can be&#xD;
      reversed by use anticholinergic 6 hours post BCG instillation Anti-inflammatory drugs&#xD;
      significantly reduced BCG-induced granulocyte activation and did not impair BCG-induced&#xD;
      lymphocyte cytotoxicity against bladder tumor cells in mice. The committee of International&#xD;
      Bladder Cancer Group (IBCG) recommend use of anti-inflammatory agents (NSAIDs) for treatment&#xD;
      of non-bacterial or chemical cystitis and other systemic BCG side effect.&#xD;
&#xD;
      Fluoroquinolone with tuberculostatic properties, has been shown to significantly prolong&#xD;
      survival in mice with BCG systemic infection and did not affect the antitumor efficacy of&#xD;
      BCG. ofloxacin significantly decreased by 18.5% the incidence of class II or higher moderate&#xD;
      and severe adverse events of BCG.&#xD;
&#xD;
      Because of sparse published studies on BCG side effect management, the 2016 European&#xD;
      Association of Urology (EAU) guidelines management options for side effects associated with&#xD;
      intravesical BCG modify the IBCG committee clinical practice without any degree of&#xD;
      recommendation. So, in this study the investigators will try to fill the gap in the&#xD;
      literature.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">February 1, 2017</start_date>
  <completion_date type="Anticipated">December 2019</completion_date>
  <primary_completion_date type="Anticipated">December 2017</primary_completion_date>
  <phase>Phase 4</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>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Comparing the drugs efficacy on decreasing systemic and local side effects of BCG</measure>
    <time_frame>6 weeks</time_frame>
    <description>__ Outcome Measure by Four-class classification grid of BCG adverse events</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Comparing the drugs effect on decreasing voiding and storage urinary symptoms of BCG</measure>
    <time_frame>6 weeks</time_frame>
    <description>__ Outcome Measure by overactive bladder symptoms scores and American Urological Association Symptom Index</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prostatic specific antigen (PSA) change</measure>
    <time_frame>1 month and 3 months</time_frame>
    <description>__ Outcome Measure by PSA measure 1 and 3 months post instillation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>recurrence free survival</measure>
    <time_frame>1 year</time_frame>
    <description>__ Outcome Measure by Number of patients surviving for one year without tumor recurrence will be counted and compared</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">150</enrollment>
  <condition>Non-Muscle-invasive Bladder Cancer (NMIBC)</condition>
  <condition>Bacillus Calmette-Guerin (BCG) Cystitis</condition>
  <condition>Intra-vesical Instillation</condition>
  <arm_group>
    <arm_group_label>solifenacin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>(Sofenacin ''solifenacin 10 m'') [Marcyrl Pharmaceutical Industries - Egypt]</description>
  </arm_group>
  <arm_group>
    <arm_group_label>levofloxacin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>(Tavanic ''levofloxacin 500 mg'') [Sanofi-Aventis - Egypt]</description>
  </arm_group>
  <arm_group>
    <arm_group_label>lornoxicam</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>(Xefo ''lornoxicam 8 mg'') [Multi-Apex - Egypt, under license of: NYCOMED, Austria]</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>sofenacin</intervention_name>
    <description>solifenacin 10 mg, 6 hours after IVI of BCG and continue for another 2 days post instillation</description>
    <arm_group_label>solifenacin</arm_group_label>
    <other_name>Solfenacin 10 mg</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tavanic</intervention_name>
    <description>levofloxacin 500 mg, 6 hours after IVI of BCG and continue for another 2 days post instillation.</description>
    <arm_group_label>levofloxacin</arm_group_label>
    <other_name>levofloxacin 500</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Xefo</intervention_name>
    <description>lornoxicam 8 mg, 6 hours after IVI of BCG and continue for another 2 days post instillation.</description>
    <arm_group_label>lornoxicam</arm_group_label>
    <other_name>lornoxicam</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        • Patients classified as intermediate or high risk of the bladder tumour&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient over 80 years (natural decline in immune system function)&#xD;
&#xD;
          -  Refuse to complete study requirements&#xD;
&#xD;
          -  Contraindication to BCG therapy&#xD;
&#xD;
          -  High post-void residual (PVR) above 85 ml&#xD;
&#xD;
          -  American Urological Association (AUA) Symptoms score above 20&#xD;
&#xD;
          -  Sensitivity to previously mentioned 3 drugs&#xD;
&#xD;
          -  High serum creatinine&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hassan Abol-Enein, MD, Phd</last_name>
    <role>Study Chair</role>
    <affiliation>Urology and Nephrology Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ahmed Mosbah, MD</last_name>
    <role>Study Director</role>
    <affiliation>Urology and Nephrology Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ahmed Elhussein, MBBCH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Urology and Nephrology Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ahmed Elkarta, MBBCH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Urology and Nephrology Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mohamed Soltan</last_name>
    <role>Principal Investigator</role>
    <affiliation>Urology and Nephrology Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Urology and Nephrology Center</name>
      <address>
        <city>Mansoura</city>
        <state>Aldakahlia</state>
        <zip>35516</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>January 15, 2017</study_first_submitted>
  <study_first_submitted_qc>January 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 31, 2017</study_first_posted>
  <last_update_submitted>May 19, 2017</last_update_submitted>
  <last_update_submitted_qc>May 19, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 23, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mansoura University</investigator_affiliation>
    <investigator_full_name>Abdelwahab Hashem</investigator_full_name>
    <investigator_title>Urology Msc, Oncology fellow at Urology and Nephrology Center, Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>BCG Cystitis</keyword>
  <keyword>Bladder Cancer</keyword>
  <keyword>Levofloxacin</keyword>
  <keyword>Solifenacin</keyword>
  <keyword>Lornoxicam</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Urinary Bladder Neoplasms</mesh_term>
    <mesh_term>Non-Muscle Invasive Bladder Neoplasms</mesh_term>
    <mesh_term>Cystitis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Levofloxacin</mesh_term>
    <mesh_term>Lornoxicam</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>meta-analyses by contact the Prof. Hassan Abol-Enein, MD, Phd (Study Chair)</ipd_description>
  </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/NCT03038321
org study id: R/17.01.02
nct id: NCT03038321
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Compare the different supposed clinical treatment of side effects associated with
      intravesical BCG by levofloxacin (quinolones) vs solifenacin (selective anti-muscarinic) vs
      lornoxicam (NSAID)
For urothelial carcinoma (UC), which accounts for over 90% of bladder cancers, more than 70%
      of bladder cancer patients present with non-muscle-invasive disease. Approximately 40-80% of
      these tumors will recur within the first year, of which 10-25% will progress to
      muscle-invasive disease.

      Intravesical treatments with cytotoxic chemotherapy and immunotherapy have become the
      mainstay following transurethral resection (TUR). Increasing knowledge of BCG use allows for
      effective management of these once debilitating side effects. The majority of patients will
      still experience cystitis-like symptoms to some degree, including urinary frequency (71%),
      cystitis (67%), fever (25%), and hematuria (23%).

      Oxybutynin increases in fever, flu-like symptoms, dry mouth and constipation. However, in
      this study oxybutynin started the night before treatment causing an element of incomplete
      bladder emptying and allowing an increased BCG dwell time. We think that these effect can be
      reversed by use anticholinergic 6 hours post BCG instillation Anti-inflammatory drugs
      significantly reduced BCG-induced granulocyte activation and did not impair BCG-induced
      lymphocyte cytotoxicity against bladder tumor cells in mice. The committee of International
      Bladder Cancer Group (IBCG) recommend use of anti-inflammatory agents (NSAIDs) for treatment
      of non-bacterial or chemical cystitis and other systemic BCG side effect.

      Fluoroquinolone with tuberculostatic properties, has been shown to significantly prolong
      survival in mice with BCG systemic infection and did not affect the antitumor efficacy of
      BCG. ofloxacin significantly decreased by 18.5% the incidence of class II or higher moderate
      and severe adverse events of BCG.

      Because of sparse published studies on BCG side effect management, the 2016 European
      Association of Urology (EAU) guidelines management options for side effects associated with
      intravesical BCG modify the IBCG committee clinical practice without any degree of
      recommendation. So, in this study the investigators will try to fill the gap in the
      literature.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Comparing the drugs efficacy on decreasing systemic and local side effects of BCG
time frame: 6 weeks
description: __ Outcome Measure by Four-class classification grid of BCG adverse events
measure: Comparing the drugs effect on decreasing voiding and storage urinary symptoms of BCG
time frame: 6 weeks
description: __ Outcome Measure by overactive bladder symptoms scores and American Urological Association Symptom Index
measure: Prostatic specific antigen (PSA) change
time frame: 1 month and 3 months
description: __ Outcome Measure by PSA measure 1 and 3 months post instillation
measure: recurrence free survival
time frame: 1 year
description: __ Outcome Measure by Number of patients surviving for one year without tumor recurrence will be counted and compared
arm group label: solifenacin
arm group type: Active Comparator
description: (Sofenacin ''solifenacin 10 m'') [Marcyrl Pharmaceutical Industries - Egypt]
arm group label: levofloxacin
arm group type: Active Comparator
description: (Tavanic ''levofloxacin 500 mg'') [Sanofi-Aventis - Egypt]
arm group label: lornoxicam
arm group type: Active Comparator
description: (Xefo ''lornoxicam 8 mg'') [Multi-Apex - Egypt, under license of: NYCOMED, Austria]
intervention type: Drug
intervention name: sofenacin
description: solifenacin 10 mg, 6 hours after IVI of BCG and continue for another 2 days post instillation
arm group label: solifenacin
other name: Solfenacin 10 mg
intervention type: Drug
intervention name: Tavanic
description: levofloxacin 500 mg, 6 hours after IVI of BCG and continue for another 2 days post instillation.
arm group label: levofloxacin
other name: levofloxacin 500
intervention type: Drug
intervention name: Xefo
description: lornoxicam 8 mg, 6 hours after IVI of BCG and continue for another 2 days post instillation.
arm group label: lornoxicam
other name: lornoxicam
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Hassan Abol-Enein, MD, Phd
role: Study Chair
affiliation: Urology and Nephrology Center
last name: Ahmed Mosbah, MD
role: Study Director
affiliation: Urology and Nephrology Center
last name: Ahmed Elhussein, MBBCH
role: Principal Investigator
affiliation: Urology and Nephrology Center
last name: Ahmed Elkarta, MBBCH
role: Principal Investigator
affiliation: Urology and Nephrology Center
last name: Mohamed Soltan
role: Principal Investigator
affiliation: Urology and Nephrology Center
facility: 
country: Egypt
responsible party type: Principal Investigator
investigator affiliation: Mansoura University
investigator full name: Abdelwahab Hashem
investigator title: Urology Msc, Oncology fellow at Urology and Nephrology Center, Principal Investigator
mesh term: Urinary Bladder Neoplasms
mesh term: Non-Muscle Invasive Bladder Neoplasms
mesh term: Cystitis
mesh term: Levofloxacin
mesh term: Lornoxicam
sharing ipd: Yes
ipd description: meta-analyses by contact the Prof. Hassan Abol-Enein, MD, Phd (Study Chair)