<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/NCT02200328</url>
  </required_header>
  <id_info>
    <org_study_id>FLA14-061</org_study_id>
    <nct_id>NCT02200328</nct_id>
  </id_info>
  <brief_title>Efficacy of Metronidazole Prophylaxis Against Clostridium Difficile-Associated Diarrhea in High Risk Adult Patients</brief_title>
  <official_title>Efficacy of Metronidazole Prophylaxis Against Clostridium Difficile-Associated Diarrhea in High Risk Adult Patients: A Randomized Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Alison Schneider</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The Cleveland Clinic</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to test if metronidazole prophylaxis is effective in decreasing&#xD;
      the incidence of hospital induced Clostridium Difficile diarrhea among patients at high risk&#xD;
      for this infection.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Clostridium Difficile infection or C. Diff (CDI) is an infection that causes severe diarrhea.&#xD;
      Risk factors for this infection include hospitalization, the use of antibiotics, along with&#xD;
      medications that decrease the acid in the stomach. This infection leads to a disease which is&#xD;
      difficult to treat and can cause serious complications including death in rare cases. This&#xD;
      infection also increases medical costs by prolonging hospital stays.&#xD;
&#xD;
      Metronidazole (known by the brand name Flagyl) is an antibiotic that has been available for&#xD;
      decades and has been used to treat this disease. Flagyl is approved by the Food and Drug&#xD;
      Administration for the treatment of C. diff infection. Recent research by the investigators&#xD;
      group has shown that hospitalized patients who took Flagyl had a decreased chance of getting&#xD;
      C. Diff infection. However, high quality studies are needed to better evaluate whether the&#xD;
      investigators can prevent C. Diff infection in high risk patients with the use of Flagyl.&#xD;
&#xD;
      The purpose of this study is to assess if metronidazole prophylaxis is effective in&#xD;
      decreasing the incidence of hospital induced Clostridium Difficile diarrhea among inpatients&#xD;
      at high risk for this infection.&#xD;
&#xD;
      High risk patient population are as defined below: taking a broad spectrum antibiotics&#xD;
      (piperacillin/tazobactam-Zosyn; Ciprofloxacin).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Patients noncompliant with instructions and follow ups could not be completed.&#xD;
  </why_stopped>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">March 2016</completion_date>
  <primary_completion_date type="Actual">March 2016</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>Prevention</primary_purpose>
    <masking>Single (Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The Incidence of Clostridium Difficile Diarrhea in Both Study Groups at 30 Days Post Broad Spectrum Antibiotic Use.</measure>
    <time_frame>30 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Determine Differences in Clostridium Difficile Diarrhea Incidence Between Patients on Piperacillin/Tazobactam vs. Patients on Ciprofloxacin.</measure>
    <time_frame>30 days</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">76</enrollment>
  <condition>Clostridium Difficile Diarrhea</condition>
  <arm_group>
    <arm_group_label>Metronidazole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Metronidazole tablets 500mg orally or IV , 3 times a day for a maximum of 14 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo(Corn starch pill) orally 3 times a day for a maximum of 14 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metronidazole</intervention_name>
    <description>Metronidazole tablets 500mg orally or IV , 3 times a day for a maximum of 14 days</description>
    <arm_group_label>Metronidazole</arm_group_label>
    <other_name>Flagyl</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo(Corn starch pill) orally 3 times a day for a maximum of 14 days</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>corn starch pill</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Inpatients &gt;55&#xD;
&#xD;
          -  Proton Pump inhibitor / Histamine-2 Blocker&#xD;
&#xD;
          -  On broad spectrum antibiotics (Zosyn and/or Ciprofloxacin). These two antibiotics are&#xD;
             selected based on current hospital formulary/use&#xD;
&#xD;
          -  Anticipated hospital stay &gt;48 hours&#xD;
&#xD;
          -  Mental capacity (able to give informed written consent).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Admission for CDI&#xD;
&#xD;
          -  Existing diarrhea at admission&#xD;
&#xD;
          -  Passed prophylactic window (&gt;48 hours on broad spectrum antibiotics)&#xD;
&#xD;
          -  Unable to take PO at the time of evaluation for study entry&#xD;
&#xD;
          -  No more than 14 days of broad spectrum antibiotics anticipated&#xD;
&#xD;
          -  Medications with serious interactions/contraindications to that would be taken&#xD;
             together with metronidazole (ex. Warfarin, disulfiram, phenytoin, calcineurin&#xD;
             inhibitors)&#xD;
&#xD;
          -  Inflammatory Bowel Disease&#xD;
&#xD;
          -  Admission for colonic bowel surgery or h/o total/Subtotal colectomy)&#xD;
&#xD;
          -  Hospice&#xD;
&#xD;
          -  Mortality expected &lt;7days&#xD;
&#xD;
          -  Previous CDI in the past 6 months&#xD;
&#xD;
          -  Intensive care admission due to the difficulty of monitoring them&#xD;
&#xD;
          -  Allergy to Metronidazole or other Antibiotics in protocol&#xD;
&#xD;
          -  Patients with neuropathy&#xD;
&#xD;
          -  History of heavy ethyl alcohol intake(greater than 3 drinks daily) or intake in past&#xD;
             24 hours,Solid organ transplant.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>55 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alison Schneider, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cleveland Clinic Florida</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cleveland Clinic Florida</name>
      <address>
        <city>Weston</city>
        <state>Florida</state>
        <zip>33331</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2017</verification_date>
  <study_first_submitted>July 21, 2014</study_first_submitted>
  <study_first_submitted_qc>July 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 25, 2014</study_first_posted>
  <results_first_submitted>March 29, 2016</results_first_submitted>
  <results_first_submitted_qc>May 4, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">June 10, 2016</results_first_posted>
  <last_update_submitted>April 17, 2017</last_update_submitted>
  <last_update_submitted_qc>April 17, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 17, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Cleveland Clinic Florida</investigator_affiliation>
    <investigator_full_name>Alison Schneider</investigator_full_name>
    <investigator_title>M.D</investigator_title>
  </responsible_party>
  <keyword>Clostridium difficile infection</keyword>
  <keyword>Diarrhea</keyword>
  <keyword>Flagyl</keyword>
  <keyword>Metronidazole</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Clostridium Infections</mesh_term>
    <mesh_term>Diarrhea</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metronidazole</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Metronidazole</title>
          <description>Metronidazole tablets 500mg orally or IV , 3 times a day for a maximum of 14 days&#xD;
Metronidazole: Metronidazole tablets 500mg orally or IV , 3 times a day for a maximum of 14 days</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo(Corn starch pill) orally 3 times a day for a maximum of 14 days&#xD;
Placebo: Placebo(Corn starch pill) orally 3 times a day for a maximum of 14 days</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="43"/>
                <participants group_id="P2" count="33"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="43"/>
                <participants group_id="P2" count="33"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Metronidazole</title>
          <description>Metronidazole tablets 500mg orally or IV , 3 times a day for a maximum of 14 days&#xD;
Metronidazole: Metronidazole tablets 500mg orally or IV , 3 times a day for a maximum of 14 days</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo(Corn starch pill) orally 3 times a day for a maximum of 14 days&#xD;
Placebo: Placebo(Corn starch pill) orally 3 times a day for a maximum of 14 days</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="43"/>
            <count group_id="B2" value="33"/>
            <count group_id="B3" value="76"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="71" lower_limit="55" upper_limit="96"/>
                    <measurement group_id="B2" value="71.8" lower_limit="58" upper_limit="98"/>
                    <measurement group_id="B3" value="71.4" lower_limit="55" upper_limit="98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="43"/>
                    <measurement group_id="B2" value="33"/>
                    <measurement group_id="B3" value="76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Incidence of Clostridium Difficile Diarrhea in Both Study Groups at 30 Days Post Broad Spectrum Antibiotic Use.</title>
        <time_frame>30 days</time_frame>
        <population>0 participants were analyzed due to large number of patients not complying to the instructions and loss to follow up.</population>
        <group_list>
          <group group_id="O1">
            <title>Metronidazole</title>
            <description>Metronidazole tablets 500mg orally or IV , 3 times a day for a maximum of 14 days&#xD;
Metronidazole: Metronidazole tablets 500mg orally or IV , 3 times a day for a maximum of 14 days</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo(Corn starch pill) orally 3 times a day for a maximum of 14 days&#xD;
Placebo: Placebo(Corn starch pill) orally 3 times a day for a maximum of 14 days</description>
          </group>
        </group_list>
        <measure>
          <title>The Incidence of Clostridium Difficile Diarrhea in Both Study Groups at 30 Days Post Broad Spectrum Antibiotic Use.</title>
          <population>0 participants were analyzed due to large number of patients not complying to the instructions and loss to follow up.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Determine Differences in Clostridium Difficile Diarrhea Incidence Between Patients on Piperacillin/Tazobactam vs. Patients on Ciprofloxacin.</title>
        <time_frame>30 days</time_frame>
        <population>0 participants were analyzed due to large number of patients not complying to the instructions and loss to follow up.</population>
        <group_list>
          <group group_id="O1">
            <title>Metronidazole</title>
            <description>Metronidazole tablets 500mg orally or IV , 3 times a day for a maximum of 14 days&#xD;
Metronidazole: Metronidazole tablets 500mg orally or IV , 3 times a day for a maximum of 14 days</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo(Corn starch pill) orally 3 times a day for a maximum of 14 days&#xD;
Placebo: Placebo(Corn starch pill) orally 3 times a day for a maximum of 14 days</description>
          </group>
        </group_list>
        <measure>
          <title>Determine Differences in Clostridium Difficile Diarrhea Incidence Between Patients on Piperacillin/Tazobactam vs. Patients on Ciprofloxacin.</title>
          <population>0 participants were analyzed due to large number of patients not complying to the instructions and loss to follow up.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Metronidazole</title>
          <description>Metronidazole tablets 500mg orally or IV , 3 times a day for a maximum of 14 days&#xD;
Metronidazole: Metronidazole tablets 500mg orally or IV , 3 times a day for a maximum of 14 days</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo(Corn starch pill) orally 3 times a day for a maximum of 14 days&#xD;
Placebo: Placebo(Corn starch pill) orally 3 times a day for a maximum of 14 days</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Early termination:&#xD;
Many patients did not comply with the protocol instructions.&#xD;
Lack of resources to conduct the study.&#xD;
Many patients did not respond to follow up calls.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr.Alison Schneider</name_or_title>
      <organization>Cleveland Clinic Florida</organization>
      <phone>9546595646</phone>
      <email>schneia2@ccf.org</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02200328
org study id: FLA14-061
nct id: NCT02200328
lead sponsor: 
has dmc: Yes
The purpose of this study is to test if metronidazole prophylaxis is effective in decreasing
      the incidence of hospital induced Clostridium Difficile diarrhea among patients at high risk
      for this infection.
Clostridium Difficile infection or C. Diff (CDI) is an infection that causes severe diarrhea.
      Risk factors for this infection include hospitalization, the use of antibiotics, along with
      medications that decrease the acid in the stomach. This infection leads to a disease which is
      difficult to treat and can cause serious complications including death in rare cases. This
      infection also increases medical costs by prolonging hospital stays.

      Metronidazole (known by the brand name Flagyl) is an antibiotic that has been available for
      decades and has been used to treat this disease. Flagyl is approved by the Food and Drug
      Administration for the treatment of C. diff infection. Recent research by the investigators
      group has shown that hospitalized patients who took Flagyl had a decreased chance of getting
      C. Diff infection. However, high quality studies are needed to better evaluate whether the
      investigators can prevent C. Diff infection in high risk patients with the use of Flagyl.

      The purpose of this study is to assess if metronidazole prophylaxis is effective in
      decreasing the incidence of hospital induced Clostridium Difficile diarrhea among inpatients
      at high risk for this infection.

      High risk patient population are as defined below: taking a broad spectrum antibiotics
      (piperacillin/tazobactam-Zosyn; Ciprofloxacin).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Single (Care Provider)
measure: The Incidence of Clostridium Difficile Diarrhea in Both Study Groups at 30 Days Post Broad Spectrum Antibiotic Use.
time frame: 30 days
measure: Determine Differences in Clostridium Difficile Diarrhea Incidence Between Patients on Piperacillin/Tazobactam vs. Patients on Ciprofloxacin.
time frame: 30 days
arm group label: Metronidazole
arm group type: Experimental
description: Metronidazole tablets 500mg orally or IV , 3 times a day for a maximum of 14 days
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo(Corn starch pill) orally 3 times a day for a maximum of 14 days
intervention type: Drug
intervention name: Metronidazole
description: Metronidazole tablets 500mg orally or IV , 3 times a day for a maximum of 14 days
arm group label: Metronidazole
other name: Flagyl
intervention type: Drug
intervention name: Placebo
description: Placebo(Corn starch pill) orally 3 times a day for a maximum of 14 days
arm group label: Placebo
other name: corn starch pill
criteria: 
gender: All
minimum age: 55 Years
maximum age: N/A
healthy volunteers: No
last name: Alison Schneider, M.D.
role: Principal Investigator
affiliation: Cleveland Clinic Florida
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Cleveland Clinic Florida
investigator full name: Alison Schneider
investigator title: M.D
mesh term: Clostridium Infections
mesh term: Diarrhea
mesh term: Metronidazole
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Early termination:
Many patients did not comply with the protocol instructions.
Lack of resources to conduct the study.
Many patients did not respond to follow up calls.
point of contact: 