<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/NCT02246270</url>
  </required_header>
  <id_info>
    <org_study_id>IRB8481</org_study_id>
    <nct_id>NCT02246270</nct_id>
  </id_info>
  <brief_title>Recurrent Urinary Tract Infections and Heparin (RUTIH Trial)</brief_title>
  <official_title>Recurrent Urinary Tract Infections and Heparin: a Double-blind Randomized Trial (RUTIH Trial)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Oklahoma</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Oklahoma</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Urinary Tract Infections (UTIs) are the second most common infection in the body. UTIs&#xD;
      account for five percent of all visits to primary care physicians. Many women who have had a&#xD;
      UTI will develop recurring urinary tract infections. Recent studies suggest that some women&#xD;
      who suffer from recurrent UTIs have urinary tracts that allow bacteria to adhere to it more&#xD;
      readily than others. Women who suffered from bladder inflammation and recurrent UTIs were&#xD;
      noted to have reduced UTIs and bladder inflammation with heparin bladder instillations.&#xD;
      Heparin is a highly-sulfated glycosaminoglycan and stored within the secretory granules of&#xD;
      mast cells and released only into the vasculature at sites of tissue injury. It has been&#xD;
      proposed that, in addition to anticoagulation, the main purpose of heparin is defense at such&#xD;
      sites against invading bacteria and other foreign materials. The central question the&#xD;
      research is intended to answer is does Heparin bladder instillations decrease UTI rates in&#xD;
      patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary Objectives: The specific aims of this study are to 1) demonstrate that Heparin&#xD;
      bladder instillations reduce the number of UTI episodes; 2) demonstrate Heparin bladder&#xD;
      instillations increase median intervals between UTI; and 3) demonstrate that Heparin bladder&#xD;
      instillations decrease urine inflammatory (NGAL) levels. Study Design: This study will be a&#xD;
      randomized, double-blind, placebo-controlled trial of subjects treated for documented&#xD;
      recurrent urinary tract infections with heparin bladder instillation versus sterile saline&#xD;
      instillations. The study recruits women (n = 30) with 3 or more UTI episodes in one year from&#xD;
      the patient population at The University of Oklahoma Health Sciences Center (OUHSC) and The&#xD;
      University of Oklahoma-Tulsa (OU-Tulsa) and randomly assigns them to treatment as usual care&#xD;
      with sterile saline instillation (n =15) or treatment as usual with heparin bladder&#xD;
      instillations (n = 15). Subjects are given 6 weekly bladder instillations with interval&#xD;
      follow-ups; the primary outcome measures are number of UTI episodes during the six month&#xD;
      study period and a survival analysis assesses time to the next UTI. The usual care of this&#xD;
      study is antibiotic treatment for UTI only. Urine samples will be collected at certain&#xD;
      intervals. Analysis: We will seek a statistically significant difference of the recurrent UTI&#xD;
      rate for 6 months between heparin instillation and sterile saline instillation group.&#xD;
      Assuming Recurrent UTI rate of sterile saline bladder instillation is 2.3.3 UTI episodes per&#xD;
      six months, a 35% reduction in the recurrent UTI rate is deemed significant based on previous&#xD;
      literature. A sample size 30 (15 for each group) will achieve 60% power to detect a 35%&#xD;
      reduction in recurrent UTI rate at a 0.05 significance level. Allowing for a 25% drop out, a&#xD;
      total of 30 subjects will be required. Significance: Recurrent UTIs are challenging to&#xD;
      manage, especially if microbiological results are equivocal. In women who suffer from&#xD;
      frequent recurrences, daily antibiotic use is the most effective strategy for recurrent UTI&#xD;
      prevention compared to daily cranberry pills, daily estrogen therapy, and acupuncture.&#xD;
      However even with this traditional approach of continuous antibiotic for 6 to 12 months, the&#xD;
      rate of UTI was only reduced during prophylaxis and the rate of UTI was unchanged after&#xD;
      stopping antibiotic treatment. Increasing antibiotic resistance rates require immediate&#xD;
      identification of innovative alternative prophylactic therapies. The lack of non-antibiotic&#xD;
      therapies gives an opportunity to develop innovative strategies to decrease recurrent UTIs&#xD;
      and decrease the burden of UTIs. This study will augment the current evidence available on&#xD;
      the aggregate effects of a treatment that emphasizes the optimization of both antibiotic&#xD;
      regimens and non-antibiotic interventions.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 28, 2017</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">May 2023</primary_completion_date>
  <phase>Phase 1/Phase 2</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>Prevention</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from Baseline in UTI rate at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Will measure change from baseline in UTI rate at 6 months using statistical methods</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in median time to UTI recurrence at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Will measure change from baseline in median time to UTI recurrence at 6 months by statistical analysis</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change from Baseline in NGAL levels at 6 months(NGAL) levels after Heparin treatment</measure>
    <time_frame>6 months</time_frame>
    <description>Will measure change from baseline in NGAL levels at 6 months (NGAL) levels after Heparin treatment using statistical analysis</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Recurrent Urinary Tract Infections</condition>
  <arm_group>
    <arm_group_label>Intravesical heparin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Recurrent UTI subject receives intravesical heparin once every week for 6 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Recurrent UTI subject receives intravesical saline once every week for 6 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intravesical Heparin</intervention_name>
    <description>Heparin bladder instillation</description>
    <arm_group_label>Intravesical heparin</arm_group_label>
    <other_name>Intravesical heparin bladder instillation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Intravesical saline</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women aged 18-85 with history of recurrent urinary tract infections.&#xD;
&#xD;
               -  Definition of Recurrent UTI: if experienced either more than 3 symptomatic UTI&#xD;
                  episodes in the past year (including the index infection) or 2 such episodes in&#xD;
                  the past 6 months.&#xD;
&#xD;
               -  Definition of UTI: &gt;103 cfu/mL of a uropathogen in midstream urine culture from a&#xD;
                  woman experiencing more than 2 symptoms of cystitis (dysuria, urgency, frequency,&#xD;
                  suprapubic pain, or hematuria) or, in the absence of a culture, demonstration of&#xD;
                  pyuria on urinalysis and more than 2 urinary symptoms, as well as complete and&#xD;
                  rapid resolution of symptoms in response to antibiotic therapy for UTI.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Taking any anticoagulant such as warfarin sodium, heparin&#xD;
&#xD;
          -  Taking any thrombolytic agent such as a tissue plasminogen activator or streptokinase&#xD;
&#xD;
          -  Known aneurysm, thrombocytopenia, hemorrhagic disease, hemophilia, gastrointestinal&#xD;
             ulceration, polyps, or diverticula&#xD;
&#xD;
          -  Known hypersensitivity to heparin&#xD;
&#xD;
          -  History of, or currently has neurogenic bladder, pelvic irradiation or chemical&#xD;
             cystitis&#xD;
&#xD;
          -  Presence of urethral, pelvic, or rectal carcinoma, Benign or malignant bladder tumors&#xD;
&#xD;
          -  Tuberculous cystitis, urinary schistosomiasis&#xD;
&#xD;
          -  Bladder or ureteral calculi, urethral or bladder obstruction, augmentation&#xD;
             cystoplasty, cystectomy, supratrigonal denervation of the bladder (cystolysis),&#xD;
             neurectomy, or implanted peripheral nerve stimulator that has affected bladder&#xD;
             function; Microscopic hematuria as defined as &gt; 5 red blood cells (RBC) /high power&#xD;
             field at baseline visit without a negative workup within the last year&#xD;
&#xD;
          -  Positive pregnancy test at the baseline visit, are pregnant or lactating, or are&#xD;
             planning to become pregnant during the study period&#xD;
&#xD;
          -  Have history of uterine, cervical or vaginal cancer during the past 3 years&#xD;
&#xD;
          -  Clinically significant vaginitis at baseline visit&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jameca R. Price, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Oklahoma</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jameca R Price, MD</last_name>
    <phone>918-660-8350</phone>
    <email>Jameca-Price@ouhsc.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Oklahoma-Tulsa OB/GYN Dept and OU-Physicians</name>
      <address>
        <city>Tulsa</city>
        <state>Oklahoma</state>
        <zip>74135</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jameca R Price, MD</last_name>
      <phone>918-660-8350</phone>
      <email>Jameca-Price@ouhsc.edu</email>
    </contact>
    <investigator>
      <last_name>Jameca R. Price, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>September 15, 2014</study_first_submitted>
  <study_first_submitted_qc>September 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 22, 2014</study_first_posted>
  <last_update_submitted>October 31, 2022</last_update_submitted>
  <last_update_submitted_qc>October 31, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 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>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Urinary Tract Infections</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heparin</mesh_term>
    <mesh_term>Calcium heparin</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/NCT02246270
org study id: IRB8481
nct id: NCT02246270
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Urinary Tract Infections (UTIs) are the second most common infection in the body. UTIs
      account for five percent of all visits to primary care physicians. Many women who have had a
      UTI will develop recurring urinary tract infections. Recent studies suggest that some women
      who suffer from recurrent UTIs have urinary tracts that allow bacteria to adhere to it more
      readily than others. Women who suffered from bladder inflammation and recurrent UTIs were
      noted to have reduced UTIs and bladder inflammation with heparin bladder instillations.
      Heparin is a highly-sulfated glycosaminoglycan and stored within the secretory granules of
      mast cells and released only into the vasculature at sites of tissue injury. It has been
      proposed that, in addition to anticoagulation, the main purpose of heparin is defense at such
      sites against invading bacteria and other foreign materials. The central question the
      research is intended to answer is does Heparin bladder instillations decrease UTI rates in
      patients.
Primary Objectives: The specific aims of this study are to 1) demonstrate that Heparin
      bladder instillations reduce the number of UTI episodes; 2) demonstrate Heparin bladder
      instillations increase median intervals between UTI; and 3) demonstrate that Heparin bladder
      instillations decrease urine inflammatory (NGAL) levels. Study Design: This study will be a
      randomized, double-blind, placebo-controlled trial of subjects treated for documented
      recurrent urinary tract infections with heparin bladder instillation versus sterile saline
      instillations. The study recruits women (n = 30) with 3 or more UTI episodes in one year from
      the patient population at The University of Oklahoma Health Sciences Center (OUHSC) and The
      University of Oklahoma-Tulsa (OU-Tulsa) and randomly assigns them to treatment as usual care
      with sterile saline instillation (n =15) or treatment as usual with heparin bladder
      instillations (n = 15). Subjects are given 6 weekly bladder instillations with interval
      follow-ups; the primary outcome measures are number of UTI episodes during the six month
      study period and a survival analysis assesses time to the next UTI. The usual care of this
      study is antibiotic treatment for UTI only. Urine samples will be collected at certain
      intervals. Analysis: We will seek a statistically significant difference of the recurrent UTI
      rate for 6 months between heparin instillation and sterile saline instillation group.
      Assuming Recurrent UTI rate of sterile saline bladder instillation is 2.3.3 UTI episodes per
      six months, a 35% reduction in the recurrent UTI rate is deemed significant based on previous
      literature. A sample size 30 (15 for each group) will achieve 60% power to detect a 35%
      reduction in recurrent UTI rate at a 0.05 significance level. Allowing for a 25% drop out, a
      total of 30 subjects will be required. Significance: Recurrent UTIs are challenging to
      manage, especially if microbiological results are equivocal. In women who suffer from
      frequent recurrences, daily antibiotic use is the most effective strategy for recurrent UTI
      prevention compared to daily cranberry pills, daily estrogen therapy, and acupuncture.
      However even with this traditional approach of continuous antibiotic for 6 to 12 months, the
      rate of UTI was only reduced during prophylaxis and the rate of UTI was unchanged after
      stopping antibiotic treatment. Increasing antibiotic resistance rates require immediate
      identification of innovative alternative prophylactic therapies. The lack of non-antibiotic
      therapies gives an opportunity to develop innovative strategies to decrease recurrent UTIs
      and decrease the burden of UTIs. This study will augment the current evidence available on
      the aggregate effects of a treatment that emphasizes the optimization of both antibiotic
      regimens and non-antibiotic interventions.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Investigator)
measure: Change from Baseline in UTI rate at 6 months
time frame: 6 months
description: Will measure change from baseline in UTI rate at 6 months using statistical methods
measure: Change from Baseline in median time to UTI recurrence at 6 months
time frame: 6 months
description: Will measure change from baseline in median time to UTI recurrence at 6 months by statistical analysis
measure: Change from Baseline in NGAL levels at 6 months(NGAL) levels after Heparin treatment
time frame: 6 months
description: Will measure change from baseline in NGAL levels at 6 months (NGAL) levels after Heparin treatment using statistical analysis
arm group label: Intravesical heparin
arm group type: Experimental
description: Recurrent UTI subject receives intravesical heparin once every week for 6 weeks
arm group label: Placebo
arm group type: Active Comparator
description: Recurrent UTI subject receives intravesical saline once every week for 6 weeks
intervention type: Drug
intervention name: Intravesical Heparin
description: Heparin bladder instillation
arm group label: Intravesical heparin
other name: Intravesical heparin bladder instillation
intervention type: Other
intervention name: Placebo
description: Intravesical saline
arm group label: Placebo
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Jameca R. Price, MD
role: Principal Investigator
affiliation: University of Oklahoma
last name: Jameca R Price, MD
phone: 918-660-8350
email: Jameca-Price@ouhsc.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Urinary Tract Infections
mesh term: Recurrence
mesh term: Heparin
mesh term: Calcium heparin