<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/NCT01694069</url>
  </required_header>
  <id_info>
    <org_study_id>24255</org_study_id>
    <nct_id>NCT01694069</nct_id>
  </id_info>
  <brief_title>Continuous Infusion Piperacillin-tazobactam for the Treatment of Cystic Fibrosis</brief_title>
  <acronym>PIPE-CF</acronym>
  <official_title>Continuous Infusion Piperacillin-Tazobactam for the Treatment of Pulmonary Exacerbations in Patients With Cystic Fibrosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>West Virginia University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>West Virginia University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Cystic fibrosis is an inherited disorder leading to chronic pulmonary inflammation and&#xD;
      infection. A majority of people with cystic fibrosis have large quantities of bacteria&#xD;
      residing in their lungs. One of the most common and harmful bacteria is called Pseudomonas&#xD;
      aeruginosa.&#xD;
&#xD;
      Patients with cystic fibrosis require frequent therapy with intravenous (I.V.) antibiotics to&#xD;
      treat lung infections thought to be caused by Pseudomonas aeruginosa. One of the antibiotics&#xD;
      frequently used to treat this bacteria is piperacillin-tazobactam. Piperacillin-tazobactam is&#xD;
      thought to be the most effective when there is a constant level of drug in the body. The&#xD;
      standard way to administer piperacillin-tazobactam is to give several grams 4 times each day&#xD;
      as a 30 minute infusion. An alternative way to give piperacillin-tazobactam is by a&#xD;
      continuous infusion; a continuous infusion will make it more likely that drug will remain at&#xD;
      a constant level in the body. The objective of this study is to determine if administering&#xD;
      piperacillin-tazobactam as a continuous infusion is more effective at treating people having&#xD;
      a pulmonary exacerbation of cystic fibrosis than a standard 30 minute infusion, 4 times a&#xD;
      day.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      All patients will receive combination therapy to include piperacillin-tazobactam 400&#xD;
      mg/kg/day (based on piperacillin component, actual body weight) not to exceed 16 grams and&#xD;
      tobramycin 12 mg/kg/day extended interval dosing (once daily). Patients randomized to the&#xD;
      continuous infusion group will receive a one-time loading dose of 100 mg/kg over 30 minutes&#xD;
      followed immediately by initiation of the continuous infusion.&#xD;
&#xD;
      Other antibiotics with activity against Pseudomonas aeruginosa are not allowed. Patients may&#xD;
      receive an antibiotic for treatment of Staphylococcus aureus if deemed appropriate.&#xD;
&#xD;
      Other treatments for pulmonary exacerbation of cystic fibrosis will be left up to the control&#xD;
      of the treating physician. Patients will receive a total of 14 days of therapy. If deemed&#xD;
      appropriate, patients may be discharged to home where they will continue to receive blinded&#xD;
      treatment via an infusion pump. Patients will be evaluated after completing their 14 day&#xD;
      course of antibiotics (end of therapy).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Recruitment was not sufficient to complete the study&#xD;
  </why_stopped>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">September 2013</completion_date>
  <primary_completion_date type="Actual">September 2013</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Forced Expiratory Volume at One Second (FEV1)</measure>
    <time_frame>Baseline, Day 0, and Day 14</time_frame>
    <description>FEV1 will be measured upon enrollment (day 0). FEV1 will also be measured at end of therapy (day 14). If FEV1 is available when patient was stable, prior to enrollment, this value will be treated as baseline FEV1. Change in FEV1 will be calculated from baseline (if available) to day 14 and also Day 0 to day 14</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Piperacillin Serum Concentrations</measure>
    <time_frame>Day 3</time_frame>
    <description>Serum piperacillin concentration will be measured as follows:&#xD;
Intermittent infusion arm: prior to dose (trough), 30 minutes (after completion of infusion), and at 4 hours&#xD;
Continuous infusion arm: collected at the same time as in the intermittent infusion arm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Next Pulmonary Exacerbation</measure>
    <time_frame>Patients will be followed up to 52 weeks from time of enrollment</time_frame>
    <description>Patients will be followed for time of next subsequent pulmonary exacerbation for up to 52 weeks after completion of receiving study drug. Next pulmonary exacerbation is defined as requiring admission to a hospital for receipt of I.V. antibiotics because of a diagnosis of pulmonary exacerbation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Score</measure>
    <time_frame>Day 0 and day 14</time_frame>
    <description>The validated CFQ-R will be administered to patients at time of enrollment at end of therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Sputum Density of Pseudomonas Aeruginosa</measure>
    <time_frame>Day 0, day 3, and day 14</time_frame>
    <description>Sputum density of Pseudomonas aeruginosa will be determined at enrollment, day 3, and at end of therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Weight</measure>
    <time_frame>Day 0 and day 14</time_frame>
    <description>The change in weight will be documented from enrollment to end of therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Defervescence</measure>
    <time_frame>Day 0 to day 14</time_frame>
    <description>Temperature will be taken multiple times daily according to standard of care. If patients present febrile, time until patient is afebrile and remains afebrile for 24 hours will be recorded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Normalization of White Blood Cell Count</measure>
    <time_frame>Day to day 14</time_frame>
    <description>White blood cell (WBC) count will be measured once daily. If patient presents with WBC count greater than 11.0 x 10^3/mL, time until patient has WBC less than 11.0 x 10^3/mL will be recorded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Failure of Treatment</measure>
    <time_frame>Day 14</time_frame>
    <description>Failure of treatment will be defined as patient needing I.V. antibiotics beyond the 14 days allowed in this study. The primary medical team (along with a blinded investigator) treating the patient will determine whether patient requires additional therapy.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Cystic Fibrosis</condition>
  <arm_group>
    <arm_group_label>Intermittent Infusion piperacillin-tazobactam</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams), divided in four equal doses, administered over 30 minutes, four times a day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Continuous infusion piperacillin-tazobactam</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams) as a continuous infusion over 24 hours, once daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Piperacillin-tazobactam combination product</intervention_name>
    <description>400 mg/kg/day as either intermittent or continuous infusion</description>
    <arm_group_label>Continuous infusion piperacillin-tazobactam</arm_group_label>
    <arm_group_label>Intermittent Infusion piperacillin-tazobactam</arm_group_label>
    <other_name>Zosyn</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Diagnosis of cystic fibrosis&#xD;
&#xD;
          2. 8 years of age or greater&#xD;
&#xD;
          3. Chronic or intermittent infection with Pseudomonas aeruginosa as defined by the Leeds&#xD;
             Criteria&#xD;
&#xD;
          4. Pulmonary exacerbation as defined by Fuchs et al.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Admission for greater than 48 hours prior to enrollment&#xD;
&#xD;
          2. Isolation of Burkholderia spp. in a respiratory tract culture in the prior 12 months&#xD;
&#xD;
          3. Current treatment for allergic bronchopulmonary aspergillosis&#xD;
&#xD;
          4. Pregnant or breast feeding&#xD;
&#xD;
          5. History of solid organ transplantation&#xD;
&#xD;
          6. Renal impairment at time of randomization (&lt; 40 mL/min as calculated by the&#xD;
             Cockcroft-Gault equation24 ¬for adults or the Schwartz equation45 for those &lt; 18 years&#xD;
             of age) or receipt of hemodialysis&#xD;
&#xD;
          7. Allergy to study medication&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>8 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lisa Biondo, PharmD</last_name>
    <role>Principal Investigator</role>
    <affiliation>West Virginia University Healthcare</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>West Virginia University Healthcare</name>
      <address>
        <city>Morgantown</city>
        <state>West Virginia</state>
        <zip>26505</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>September 19, 2012</study_first_submitted>
  <study_first_submitted_qc>September 24, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 26, 2012</study_first_posted>
  <results_first_submitted>December 22, 2020</results_first_submitted>
  <results_first_submitted_qc>January 28, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">February 1, 2022</results_first_posted>
  <last_update_submitted>January 28, 2022</last_update_submitted>
  <last_update_submitted_qc>January 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 1, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>piperacillin</keyword>
  <keyword>tazobactam</keyword>
  <keyword>pseudomonas aeruginosa</keyword>
  <keyword>cystic fibrosis</keyword>
  <keyword>pulmonary exacerbation</keyword>
  <keyword>continuous infusion</keyword>
  <keyword>beta lactam</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cystic Fibrosis</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tazobactam</mesh_term>
    <mesh_term>Piperacillin</mesh_term>
    <mesh_term>Piperacillin, Tazobactam Drug Combination</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study was terminated and the original PI has left the institution. Minimal results information is available; all efforts were made to retrieve more results information, but were unsuccessful. The available data does not indicate in which arm the participants were enrolled, therefore all available study data with be entered under All Study Participants.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>All Study Participants</title>
          <description>Intermittent Infusion piperacillin-tazobactam and Continuous infusion piperacillin-tazobactam were combined into the All Study Participants, because the available study data was not separated into arms.&#xD;
Continuous infusion piperacillin-tazobactam:&#xD;
Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams), divided in four equal doses, administered over 30 minutes, four times a day&#xD;
Continuous infusion piperacillin-tazobactam:&#xD;
Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams) as a continuous infusion over 24 hours, once daily&#xD;
Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The study was terminated and the original PI has left the institution. Minimal results information is available; all efforts were made to retrieve more results information, but were unsuccessful. The available data does not indicate in which arm the participants were enrolled, therefore all available study data with be entered under All Study Participants.</population>
      <group_list>
        <group group_id="B1">
          <title>All Study Participants</title>
          <description>Intermittent Infusion piperacillin-tazobactam and Continuous infusion piperacillin-tazobactam were combined into the All Study Participants, because the available study data was not separated into arms.&#xD;
Continuous infusion piperacillin-tazobactam:&#xD;
Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams), divided in four equal doses, administered over 30 minutes, four times a day&#xD;
Continuous infusion piperacillin-tazobactam:&#xD;
Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams) as a continuous infusion over 24 hours, once daily&#xD;
Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <description>There was no available information about age of participants outside of that included in the inclusion criteria, indicating participants needed to be at least 8 years old to participate.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Between 8 and 99 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </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="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </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="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Forced Expiratory Volume at One Second (FEV1)</title>
        <description>FEV1 will be measured upon enrollment (day 0). FEV1 will also be measured at end of therapy (day 14). If FEV1 is available when patient was stable, prior to enrollment, this value will be treated as baseline FEV1. Change in FEV1 will be calculated from baseline (if available) to day 14 and also Day 0 to day 14</description>
        <time_frame>Baseline, Day 0, and Day 14</time_frame>
        <population>The study was terminated and the original PI has left the institution. No outcome measure results information is available; all efforts were to made to retrieve results information, but efforts were unsuccessful.</population>
        <group_list>
          <group group_id="O1">
            <title>Intermittent Infusion Piperacillin-tazobactam</title>
            <description>Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams), divided in four equal doses, administered over 30 minutes, four times a day&#xD;
Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion</description>
          </group>
          <group group_id="O2">
            <title>Continuous Infusion Piperacillin-tazobactam</title>
            <description>Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams) as a continuous infusion over 24 hours, once daily&#xD;
Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Forced Expiratory Volume at One Second (FEV1)</title>
          <description>FEV1 will be measured upon enrollment (day 0). FEV1 will also be measured at end of therapy (day 14). If FEV1 is available when patient was stable, prior to enrollment, this value will be treated as baseline FEV1. Change in FEV1 will be calculated from baseline (if available) to day 14 and also Day 0 to day 14</description>
          <population>The study was terminated and the original PI has left the institution. No outcome measure results information is available; all efforts were to made to retrieve results information, but efforts were unsuccessful.</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>Piperacillin Serum Concentrations</title>
        <description>Serum piperacillin concentration will be measured as follows:&#xD;
Intermittent infusion arm: prior to dose (trough), 30 minutes (after completion of infusion), and at 4 hours&#xD;
Continuous infusion arm: collected at the same time as in the intermittent infusion arm</description>
        <time_frame>Day 3</time_frame>
        <population>The study was terminated and the original PI has left the institution. No outcome measure results information is available; all efforts were to made to retrieve results information, but efforts were unsuccessful.</population>
        <group_list>
          <group group_id="O1">
            <title>Intermittent Infusion Piperacillin-tazobactam</title>
            <description>Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams), divided in four equal doses, administered over 30 minutes, four times a day&#xD;
Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion</description>
          </group>
          <group group_id="O2">
            <title>Continuous Infusion Piperacillin-tazobactam</title>
            <description>Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams) as a continuous infusion over 24 hours, once daily&#xD;
Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Piperacillin Serum Concentrations</title>
          <description>Serum piperacillin concentration will be measured as follows:&#xD;
Intermittent infusion arm: prior to dose (trough), 30 minutes (after completion of infusion), and at 4 hours&#xD;
Continuous infusion arm: collected at the same time as in the intermittent infusion arm</description>
          <population>The study was terminated and the original PI has left the institution. No outcome measure results information is available; all efforts were to made to retrieve results information, but efforts were unsuccessful.</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>Time to Next Pulmonary Exacerbation</title>
        <description>Patients will be followed for time of next subsequent pulmonary exacerbation for up to 52 weeks after completion of receiving study drug. Next pulmonary exacerbation is defined as requiring admission to a hospital for receipt of I.V. antibiotics because of a diagnosis of pulmonary exacerbation.</description>
        <time_frame>Patients will be followed up to 52 weeks from time of enrollment</time_frame>
        <population>The study was terminated and the original PI has left the institution. No outcome measure results information is available; all efforts were to made to retrieve results information, but efforts were unsuccessful.</population>
        <group_list>
          <group group_id="O1">
            <title>Intermittent Infusion Piperacillin-tazobactam</title>
            <description>Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams), divided in four equal doses, administered over 30 minutes, four times a day&#xD;
Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion</description>
          </group>
          <group group_id="O2">
            <title>Continuous Infusion Piperacillin-tazobactam</title>
            <description>Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams) as a continuous infusion over 24 hours, once daily&#xD;
Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Next Pulmonary Exacerbation</title>
          <description>Patients will be followed for time of next subsequent pulmonary exacerbation for up to 52 weeks after completion of receiving study drug. Next pulmonary exacerbation is defined as requiring admission to a hospital for receipt of I.V. antibiotics because of a diagnosis of pulmonary exacerbation.</description>
          <population>The study was terminated and the original PI has left the institution. No outcome measure results information is available; all efforts were to made to retrieve results information, but efforts were unsuccessful.</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>Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Score</title>
        <description>The validated CFQ-R will be administered to patients at time of enrollment at end of therapy</description>
        <time_frame>Day 0 and day 14</time_frame>
        <population>The study was terminated and the original PI has left the institution. No outcome measure results information is available; all efforts were to made to retrieve results information, but efforts were unsuccessful.</population>
        <group_list>
          <group group_id="O1">
            <title>Intermittent Infusion Piperacillin-tazobactam</title>
            <description>Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams), divided in four equal doses, administered over 30 minutes, four times a day&#xD;
Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion</description>
          </group>
          <group group_id="O2">
            <title>Continuous Infusion Piperacillin-tazobactam</title>
            <description>Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams) as a continuous infusion over 24 hours, once daily&#xD;
Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Score</title>
          <description>The validated CFQ-R will be administered to patients at time of enrollment at end of therapy</description>
          <population>The study was terminated and the original PI has left the institution. No outcome measure results information is available; all efforts were to made to retrieve results information, but efforts were unsuccessful.</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>Change in Sputum Density of Pseudomonas Aeruginosa</title>
        <description>Sputum density of Pseudomonas aeruginosa will be determined at enrollment, day 3, and at end of therapy</description>
        <time_frame>Day 0, day 3, and day 14</time_frame>
        <population>The study was terminated and the original PI has left the institution. No outcome measure results information is available; all efforts were to made to retrieve results information, but efforts were unsuccessful.</population>
        <group_list>
          <group group_id="O1">
            <title>Intermittent Infusion Piperacillin-tazobactam</title>
            <description>Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams), divided in four equal doses, administered over 30 minutes, four times a day&#xD;
Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion</description>
          </group>
          <group group_id="O2">
            <title>Continuous Infusion Piperacillin-tazobactam</title>
            <description>Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams) as a continuous infusion over 24 hours, once daily&#xD;
Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Sputum Density of Pseudomonas Aeruginosa</title>
          <description>Sputum density of Pseudomonas aeruginosa will be determined at enrollment, day 3, and at end of therapy</description>
          <population>The study was terminated and the original PI has left the institution. No outcome measure results information is available; all efforts were to made to retrieve results information, but efforts were unsuccessful.</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>Change in Weight</title>
        <description>The change in weight will be documented from enrollment to end of therapy</description>
        <time_frame>Day 0 and day 14</time_frame>
        <population>The study was terminated and the original PI has left the institution. No outcome measure results information is available; all efforts were to made to retrieve results information, but efforts were unsuccessful.</population>
        <group_list>
          <group group_id="O1">
            <title>Intermittent Infusion Piperacillin-tazobactam</title>
            <description>Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams), divided in four equal doses, administered over 30 minutes, four times a day&#xD;
Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion</description>
          </group>
          <group group_id="O2">
            <title>Continuous Infusion Piperacillin-tazobactam</title>
            <description>Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams) as a continuous infusion over 24 hours, once daily&#xD;
Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Weight</title>
          <description>The change in weight will be documented from enrollment to end of therapy</description>
          <population>The study was terminated and the original PI has left the institution. No outcome measure results information is available; all efforts were to made to retrieve results information, but efforts were unsuccessful.</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>Time to Defervescence</title>
        <description>Temperature will be taken multiple times daily according to standard of care. If patients present febrile, time until patient is afebrile and remains afebrile for 24 hours will be recorded.</description>
        <time_frame>Day 0 to day 14</time_frame>
        <population>The study was terminated and the original PI has left the institution. No outcome measure results information is available; all efforts were to made to retrieve results information, but efforts were unsuccessful.</population>
        <group_list>
          <group group_id="O1">
            <title>Intermittent Infusion Piperacillin-tazobactam</title>
            <description>Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams), divided in four equal doses, administered over 30 minutes, four times a day&#xD;
Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion</description>
          </group>
          <group group_id="O2">
            <title>Continuous Infusion Piperacillin-tazobactam</title>
            <description>Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams) as a continuous infusion over 24 hours, once daily&#xD;
Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Defervescence</title>
          <description>Temperature will be taken multiple times daily according to standard of care. If patients present febrile, time until patient is afebrile and remains afebrile for 24 hours will be recorded.</description>
          <population>The study was terminated and the original PI has left the institution. No outcome measure results information is available; all efforts were to made to retrieve results information, but efforts were unsuccessful.</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>Time to Normalization of White Blood Cell Count</title>
        <description>White blood cell (WBC) count will be measured once daily. If patient presents with WBC count greater than 11.0 x 10^3/mL, time until patient has WBC less than 11.0 x 10^3/mL will be recorded.</description>
        <time_frame>Day to day 14</time_frame>
        <population>The study was terminated and the original PI has left the institution. No outcome measure results information is available; all efforts were to made to retrieve results information, but efforts were unsuccessful.</population>
        <group_list>
          <group group_id="O1">
            <title>Intermittent Infusion Piperacillin-tazobactam</title>
            <description>Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams), divided in four equal doses, administered over 30 minutes, four times a day&#xD;
Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion</description>
          </group>
          <group group_id="O2">
            <title>Continuous Infusion Piperacillin-tazobactam</title>
            <description>Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams) as a continuous infusion over 24 hours, once daily&#xD;
Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Normalization of White Blood Cell Count</title>
          <description>White blood cell (WBC) count will be measured once daily. If patient presents with WBC count greater than 11.0 x 10^3/mL, time until patient has WBC less than 11.0 x 10^3/mL will be recorded.</description>
          <population>The study was terminated and the original PI has left the institution. No outcome measure results information is available; all efforts were to made to retrieve results information, but efforts were unsuccessful.</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>Clinical Failure of Treatment</title>
        <description>Failure of treatment will be defined as patient needing I.V. antibiotics beyond the 14 days allowed in this study. The primary medical team (along with a blinded investigator) treating the patient will determine whether patient requires additional therapy.</description>
        <time_frame>Day 14</time_frame>
        <population>The study was terminated and the original PI has left the institution. No outcome measure results information is available; all efforts were to made to retrieve results information, but efforts were unsuccessful.</population>
        <group_list>
          <group group_id="O1">
            <title>Intermittent Infusion Piperacillin-tazobactam</title>
            <description>Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams), divided in four equal doses, administered over 30 minutes, four times a day&#xD;
Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion</description>
          </group>
          <group group_id="O2">
            <title>Continuous Infusion Piperacillin-tazobactam</title>
            <description>Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams) as a continuous infusion over 24 hours, once daily&#xD;
Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Failure of Treatment</title>
          <description>Failure of treatment will be defined as patient needing I.V. antibiotics beyond the 14 days allowed in this study. The primary medical team (along with a blinded investigator) treating the patient will determine whether patient requires additional therapy.</description>
          <population>The study was terminated and the original PI has left the institution. No outcome measure results information is available; all efforts were to made to retrieve results information, but efforts were unsuccessful.</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>
      <desc>The study was terminated and the original PI has left the institution. No adverse event information is available; all efforts were to made to retrieve adverse event information, but efforts were unsuccessful.</desc>
      <group_list>
        <group group_id="E1">
          <title>Intermittent Infusion Piperacillin-tazobactam</title>
          <description>Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams), divided in four equal doses, administered over 30 minutes, four times a day&#xD;
Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion</description>
        </group>
        <group group_id="E2">
          <title>Continuous Infusion Piperacillin-tazobactam</title>
          <description>Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams) as a continuous infusion over 24 hours, once daily&#xD;
Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion</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="0"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</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="0"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </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>
    <point_of_contact>
      <name_or_title>Clinical Trials Compliance Coordinator</name_or_title>
      <organization>West Virginia Universtiy, WVCTSI</organization>
      <phone>304-293-0216</phone>
      <email>ctgovadmin@hsc.wvu.edu</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/NCT01694069
org study id: 24255
nct id: NCT01694069
lead sponsor: 
has dmc: No
Cystic fibrosis is an inherited disorder leading to chronic pulmonary inflammation and
      infection. A majority of people with cystic fibrosis have large quantities of bacteria
      residing in their lungs. One of the most common and harmful bacteria is called Pseudomonas
      aeruginosa.

      Patients with cystic fibrosis require frequent therapy with intravenous (I.V.) antibiotics to
      treat lung infections thought to be caused by Pseudomonas aeruginosa. One of the antibiotics
      frequently used to treat this bacteria is piperacillin-tazobactam. Piperacillin-tazobactam is
      thought to be the most effective when there is a constant level of drug in the body. The
      standard way to administer piperacillin-tazobactam is to give several grams 4 times each day
      as a 30 minute infusion. An alternative way to give piperacillin-tazobactam is by a
      continuous infusion; a continuous infusion will make it more likely that drug will remain at
      a constant level in the body. The objective of this study is to determine if administering
      piperacillin-tazobactam as a continuous infusion is more effective at treating people having
      a pulmonary exacerbation of cystic fibrosis than a standard 30 minute infusion, 4 times a
      day.
All patients will receive combination therapy to include piperacillin-tazobactam 400
      mg/kg/day (based on piperacillin component, actual body weight) not to exceed 16 grams and
      tobramycin 12 mg/kg/day extended interval dosing (once daily). Patients randomized to the
      continuous infusion group will receive a one-time loading dose of 100 mg/kg over 30 minutes
      followed immediately by initiation of the continuous infusion.

      Other antibiotics with activity against Pseudomonas aeruginosa are not allowed. Patients may
      receive an antibiotic for treatment of Staphylococcus aureus if deemed appropriate.

      Other treatments for pulmonary exacerbation of cystic fibrosis will be left up to the control
      of the treating physician. Patients will receive a total of 14 days of therapy. If deemed
      appropriate, patients may be discharged to home where they will continue to receive blinded
      treatment via an infusion pump. Patients will be evaluated after completing their 14 day
      course of antibiotics (end of therapy).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in Forced Expiratory Volume at One Second (FEV1)
time frame: Baseline, Day 0, and Day 14
description: FEV1 will be measured upon enrollment (day 0). FEV1 will also be measured at end of therapy (day 14). If FEV1 is available when patient was stable, prior to enrollment, this value will be treated as baseline FEV1. Change in FEV1 will be calculated from baseline (if available) to day 14 and also Day 0 to day 14
measure: Piperacillin Serum Concentrations
time frame: Day 3
description: Serum piperacillin concentration will be measured as follows:
Intermittent infusion arm: prior to dose (trough), 30 minutes (after completion of infusion), and at 4 hours
Continuous infusion arm: collected at the same time as in the intermittent infusion arm
measure: Time to Next Pulmonary Exacerbation
time frame: Patients will be followed up to 52 weeks from time of enrollment
description: Patients will be followed for time of next subsequent pulmonary exacerbation for up to 52 weeks after completion of receiving study drug. Next pulmonary exacerbation is defined as requiring admission to a hospital for receipt of I.V. antibiotics because of a diagnosis of pulmonary exacerbation.
measure: Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Score
time frame: Day 0 and day 14
description: The validated CFQ-R will be administered to patients at time of enrollment at end of therapy
measure: Change in Sputum Density of Pseudomonas Aeruginosa
time frame: Day 0, day 3, and day 14
description: Sputum density of Pseudomonas aeruginosa will be determined at enrollment, day 3, and at end of therapy
measure: Change in Weight
time frame: Day 0 and day 14
description: The change in weight will be documented from enrollment to end of therapy
measure: Time to Defervescence
time frame: Day 0 to day 14
description: Temperature will be taken multiple times daily according to standard of care. If patients present febrile, time until patient is afebrile and remains afebrile for 24 hours will be recorded.
measure: Time to Normalization of White Blood Cell Count
time frame: Day to day 14
description: White blood cell (WBC) count will be measured once daily. If patient presents with WBC count greater than 11.0 x 10^3/mL, time until patient has WBC less than 11.0 x 10^3/mL will be recorded.
measure: Clinical Failure of Treatment
time frame: Day 14
description: Failure of treatment will be defined as patient needing I.V. antibiotics beyond the 14 days allowed in this study. The primary medical team (along with a blinded investigator) treating the patient will determine whether patient requires additional therapy.
arm group label: Intermittent Infusion piperacillin-tazobactam
arm group type: Active Comparator
description: Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams), divided in four equal doses, administered over 30 minutes, four times a day
arm group label: Continuous infusion piperacillin-tazobactam
arm group type: Experimental
description: Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams) as a continuous infusion over 24 hours, once daily
intervention type: Drug
intervention name: Piperacillin-tazobactam combination product
description: 400 mg/kg/day as either intermittent or continuous infusion
arm group label: Continuous infusion piperacillin-tazobactam
arm group label: Intermittent Infusion piperacillin-tazobactam
other name: Zosyn
criteria: 
gender: All
minimum age: 8 Years
maximum age: N/A
healthy volunteers: No
last name: Lisa Biondo, PharmD
role: Principal Investigator
affiliation: West Virginia University Healthcare
facility: 
country: United States
responsible party type: Sponsor
mesh term: Cystic Fibrosis
mesh term: Fibrosis
mesh term: Tazobactam
mesh term: Piperacillin
mesh term: Piperacillin, Tazobactam Drug Combination
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 