<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/NCT01667094</url>
  </required_header>
  <id_info>
    <org_study_id>249/12</org_study_id>
    <secondary_id>U1111-1132-8291</secondary_id>
    <nct_id>NCT01667094</nct_id>
  </id_info>
  <brief_title>A Study Comparing Continuous Infusion Antibiotics to Standard Treatment for Lung Infections in Cystic Fibrosis</brief_title>
  <acronym>CISTIC</acronym>
  <official_title>Continuous-infusion Anti-pseudomonal β-lactams for the Treatment of Acute, Infective Pulmonary Exacerbations in Cystic Fibrosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Alfred</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The Alfred</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Cystic fibrosis (CF) is an inherited disorder which results in increased thickness of&#xD;
      secretions, especially in the lungs. By adulthood, the majority of patients with CF will have&#xD;
      a bacteria living in their lungs, called Pseudomonas aeruginosa which can cause lung&#xD;
      infections. This usually results in worsening respiratory symptoms and often an acute&#xD;
      deterioration in their lung function. They are usually treated with antibiotics that target&#xD;
      the Pseudomonas aeruginosa. These antibiotics are typically given as short intravenous&#xD;
      infusions several times a day. This study aims to compare the standard method of giving these&#xD;
      antibiotics with a different strategy of giving these antibiotics to see if this can improve&#xD;
      the outcomes of treatment of these infections and reduce the amount of Pseudomonas aeruginosa&#xD;
      in the lungs of these patients. This strategy consists of giving the same antibiotics&#xD;
      continuously, to ensure there is always enough antibiotic in the bloodstream and the lung to&#xD;
      be able to kill the bacteria.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>September 2012</start_date>
  <completion_date type="Anticipated">July 2017</completion_date>
  <primary_completion_date type="Anticipated">July 2017</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cystic Fibrosis Questionnaire-Revised respiratory component (CFQ-R) respiratory symptom score</measure>
    <time_frame>Day 0 to Day 14</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory symptom score</measure>
    <time_frame>Day 0 to Day 7, Day 0 to Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lung function testing; Forced volume expired in one second (FEV1)</measure>
    <time_frame>Day 0 to Day 7, Day 0 to Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>C-reactive peptide (CRP)</measure>
    <time_frame>Day 0 to Day 3</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quantitative bacterial load in sputum (total + Pseudomonas aeruginosa)</measure>
    <time_frame>Day 0 to Day 3, Day 0 to Day 7</time_frame>
    <description>Measured by PCR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time above minimum inhibitory concentration (MIC)</measure>
    <time_frame>Day 3</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antibiotic stability</measure>
    <time_frame>Day 3</time_frame>
    <description>For ceftazidime and meropenem, antibiotic levels will be measured from the infusion bag at the beginning and end of the infusion to determine the amount of degradation of these antibiotics.&#xD;
The temperature of the infusion bags will be monitored continuously during this time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pseudomonas aeruginosa virulence gene determinants</measure>
    <time_frame>Day 0 to Day 3 and Day 0 to Day 7</time_frame>
    <description>A panel of different previously identified virulence gene determinants for Pseudomonas aeruginosa will be measured by RNA analysis.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Cystic Fibrosis</condition>
  <arm_group>
    <arm_group_label>Intermittent, short infusion</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Infusion over 30 minutes of either:&#xD;
Cefepime 1g q8/24 OR Ceftazidime 2g q8/24 OR Meropenem 1g q8/24 OR Piperacillin-Tazobactam 4.5g q8/24 OR Ticarcillin-clavulanate 3.1g q6/24&#xD;
Antibiotic chosen by treating physician</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Continuous infusion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Continuous infusion of either:&#xD;
Cefepime 1.5g over 12h, q12/24 after initial loading dose of 500mg OR Ceftazidime 3g over 12h, q12/24 after initial loading dose 1g OR Meropenem 1.5g over 12h, q12/24 after initial loading dose 500mg OR Piperacillin-tazobactam 13.5g over 24h after initial loading dose 2.25g OR Ticarcillin-clavulanate 12.4g over 24h after initial loading dose 1.55g&#xD;
Antibiotic chosen by treating physician</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intermittent, short infusion Ceftazidime</intervention_name>
    <description>Ceftazidime 1g q8/24</description>
    <arm_group_label>Intermittent, short infusion</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Continuous infusion Ceftazidime</intervention_name>
    <description>Ceftazidime loading dose 1g infused over 30mins then 3g infused over 12h q12/24</description>
    <arm_group_label>Continuous infusion</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intermittent, short infusion Meropenem</intervention_name>
    <description>Meropenem 1g q8/24, infusion over 30 minutes</description>
    <arm_group_label>Intermittent, short infusion</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Continuous infusion Meropenem</intervention_name>
    <description>Meropenem initial loading dose of 500mg infused over 30 minutes followed by 1.5g infused over 12/24, q12/24</description>
    <arm_group_label>Continuous infusion</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intermittent, short infusion Ticarcillin-clavulanate</intervention_name>
    <description>Ticarcillin/clavulanate 3.1g q6/24</description>
    <arm_group_label>Intermittent, short infusion</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Continuous infusion Ticarcillin-clavulanate</intervention_name>
    <description>Ticarcillin-clavulanate loading dose 1.55g followed by 12.4g infused over 24/24 q24/24</description>
    <arm_group_label>Continuous infusion</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intermittent, short infusion Cefepime</intervention_name>
    <description>Cefepime 1g q8/24</description>
    <arm_group_label>Intermittent, short infusion</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Continuous infusion Cefepime</intervention_name>
    <description>Cefepime loading dose 500mg followed by 1.5g infused over 12/24, q12/24</description>
    <arm_group_label>Continuous infusion</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Continuous infusion Piperacillin tazobactam</intervention_name>
    <description>Piperacillin tazobactam loading dose of 4.5g infused over 30 minutes followed by 18g infused over 24/24, q24/24</description>
    <arm_group_label>Continuous infusion</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intermittent, short infusion Piperacillin tazobactam</intervention_name>
    <description>Piperacillin tazobactam 4.5g q6/24</description>
    <arm_group_label>Intermittent, short infusion</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients &gt;= 18 years of age,&#xD;
&#xD;
          2. Pseudomonas aeruginosa isolated in sputum within the last 12 months,&#xD;
&#xD;
          3. has an acute infective exacerbation, defined by international standards of 2 or more&#xD;
             of the following in the last 2 weeks:&#xD;
&#xD;
               -  change sputum volume or colour,&#xD;
&#xD;
               -  increased cough,&#xD;
&#xD;
               -  increased dyspnoea,&#xD;
&#xD;
               -  increased malaise, fatigue or lethargy,&#xD;
&#xD;
               -  anorexia or weight loss,&#xD;
&#xD;
               -  decrease in pulmonary function by 10% or more, or&#xD;
&#xD;
               -  new radiographic changes&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. patients &lt; 18 yrs of age,&#xD;
&#xD;
          2. patients that do not meet the criteria for an acute infective exacerbation,&#xD;
&#xD;
          3. concurrent pulmonary embolism, significant haemoptysis, pneumothorax, or respiratory&#xD;
             failure,&#xD;
&#xD;
          4. impaired renal function with an estimated creatinine clearance &lt; 60 mls/min,&#xD;
&#xD;
          5. patients allergic to ß-lactam antibiotics,&#xD;
&#xD;
          6. aminoglycoside contra-indicated,&#xD;
&#xD;
          7. intravenous antibiotics in the last 2 weeks, prior to this admission,&#xD;
&#xD;
          8. received more than 24 hours of intravenous antibiotics in this admission,&#xD;
&#xD;
          9. previous lung transplantation,&#xD;
&#xD;
         10. pregnancy or lactation, or&#xD;
&#xD;
         11. inability to consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anton Peleg, MBBS, FRACP.</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Alfred</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Alfred Hospital</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3181</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>April 2017</verification_date>
  <study_first_submitted>August 13, 2012</study_first_submitted>
  <study_first_submitted_qc>August 15, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 17, 2012</study_first_posted>
  <last_update_submitted>April 18, 2017</last_update_submitted>
  <last_update_submitted_qc>April 18, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">April 20, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Alfred</investigator_affiliation>
    <investigator_full_name>Katherine Langan</investigator_full_name>
    <investigator_title>PhD</investigator_title>
  </responsible_party>
  <keyword>Pulmonary exacerbation</keyword>
  <keyword>Continuous infusion</keyword>
  <keyword>Antipseudomonal beta-lactams</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>Meropenem</mesh_term>
    <mesh_term>Tazobactam</mesh_term>
    <mesh_term>Piperacillin</mesh_term>
    <mesh_term>Clavulanic Acid</mesh_term>
    <mesh_term>Clavulanic Acids</mesh_term>
    <mesh_term>Ceftazidime</mesh_term>
    <mesh_term>Cefepime</mesh_term>
    <mesh_term>Piperacillin, Tazobactam Drug Combination</mesh_term>
    <mesh_term>Ticarcillin</mesh_term>
    <mesh_term>Ticarcillin-clavulanic acid</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/NCT01667094
org study id: 249/12
secondary id: U1111-1132-8291
nct id: NCT01667094
lead sponsor: 
has dmc: No
Cystic fibrosis (CF) is an inherited disorder which results in increased thickness of
      secretions, especially in the lungs. By adulthood, the majority of patients with CF will have
      a bacteria living in their lungs, called Pseudomonas aeruginosa which can cause lung
      infections. This usually results in worsening respiratory symptoms and often an acute
      deterioration in their lung function. They are usually treated with antibiotics that target
      the Pseudomonas aeruginosa. These antibiotics are typically given as short intravenous
      infusions several times a day. This study aims to compare the standard method of giving these
      antibiotics with a different strategy of giving these antibiotics to see if this can improve
      the outcomes of treatment of these infections and reduce the amount of Pseudomonas aeruginosa
      in the lungs of these patients. This strategy consists of giving the same antibiotics
      continuously, to ensure there is always enough antibiotic in the bloodstream and the lung to
      be able to kill the bacteria.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Cystic Fibrosis Questionnaire-Revised respiratory component (CFQ-R) respiratory symptom score
time frame: Day 0 to Day 14
measure: Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory symptom score
time frame: Day 0 to Day 7, Day 0 to Day 28
measure: Lung function testing; Forced volume expired in one second (FEV1)
time frame: Day 0 to Day 7, Day 0 to Day 28
measure: C-reactive peptide (CRP)
time frame: Day 0 to Day 3
measure: Quantitative bacterial load in sputum (total + Pseudomonas aeruginosa)
time frame: Day 0 to Day 3, Day 0 to Day 7
description: Measured by PCR.
measure: Time above minimum inhibitory concentration (MIC)
time frame: Day 3
measure: Antibiotic stability
time frame: Day 3
description: For ceftazidime and meropenem, antibiotic levels will be measured from the infusion bag at the beginning and end of the infusion to determine the amount of degradation of these antibiotics.
The temperature of the infusion bags will be monitored continuously during this time.
measure: Pseudomonas aeruginosa virulence gene determinants
time frame: Day 0 to Day 3 and Day 0 to Day 7
description: A panel of different previously identified virulence gene determinants for Pseudomonas aeruginosa will be measured by RNA analysis.
arm group label: Intermittent, short infusion
arm group type: Active Comparator
description: Infusion over 30 minutes of either:
Cefepime 1g q8/24 OR Ceftazidime 2g q8/24 OR Meropenem 1g q8/24 OR Piperacillin-Tazobactam 4.5g q8/24 OR Ticarcillin-clavulanate 3.1g q6/24
Antibiotic chosen by treating physician
arm group label: Continuous infusion
arm group type: Experimental
description: Continuous infusion of either:
Cefepime 1.5g over 12h, q12/24 after initial loading dose of 500mg OR Ceftazidime 3g over 12h, q12/24 after initial loading dose 1g OR Meropenem 1.5g over 12h, q12/24 after initial loading dose 500mg OR Piperacillin-tazobactam 13.5g over 24h after initial loading dose 2.25g OR Ticarcillin-clavulanate 12.4g over 24h after initial loading dose 1.55g
Antibiotic chosen by treating physician
intervention type: Drug
intervention name: Intermittent, short infusion Ceftazidime
description: Ceftazidime 1g q8/24
arm group label: Intermittent, short infusion
intervention type: Drug
intervention name: Continuous infusion Ceftazidime
description: Ceftazidime loading dose 1g infused over 30mins then 3g infused over 12h q12/24
arm group label: Continuous infusion
intervention type: Drug
intervention name: Intermittent, short infusion Meropenem
description: Meropenem 1g q8/24, infusion over 30 minutes
arm group label: Intermittent, short infusion
intervention type: Drug
intervention name: Continuous infusion Meropenem
description: Meropenem initial loading dose of 500mg infused over 30 minutes followed by 1.5g infused over 12/24, q12/24
arm group label: Continuous infusion
intervention type: Drug
intervention name: Intermittent, short infusion Ticarcillin-clavulanate
description: Ticarcillin/clavulanate 3.1g q6/24
arm group label: Intermittent, short infusion
intervention type: Drug
intervention name: Continuous infusion Ticarcillin-clavulanate
description: Ticarcillin-clavulanate loading dose 1.55g followed by 12.4g infused over 24/24 q24/24
arm group label: Continuous infusion
intervention type: Drug
intervention name: Intermittent, short infusion Cefepime
description: Cefepime 1g q8/24
arm group label: Intermittent, short infusion
intervention type: Drug
intervention name: Continuous infusion Cefepime
description: Cefepime loading dose 500mg followed by 1.5g infused over 12/24, q12/24
arm group label: Continuous infusion
intervention type: Drug
intervention name: Continuous infusion Piperacillin tazobactam
description: Piperacillin tazobactam loading dose of 4.5g infused over 30 minutes followed by 18g infused over 24/24, q24/24
arm group label: Continuous infusion
intervention type: Drug
intervention name: Intermittent, short infusion Piperacillin tazobactam
description: Piperacillin tazobactam 4.5g q6/24
arm group label: Intermittent, short infusion
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Anton Peleg, MBBS, FRACP.
role: Principal Investigator
affiliation: The Alfred
facility: 
country: Australia
responsible party type: Principal Investigator
investigator affiliation: The Alfred
investigator full name: Katherine Langan
investigator title: PhD
mesh term: Cystic Fibrosis
mesh term: Fibrosis
mesh term: Meropenem
mesh term: Tazobactam
mesh term: Piperacillin
mesh term: Clavulanic Acid
mesh term: Clavulanic Acids
mesh term: Ceftazidime
mesh term: Cefepime
mesh term: Piperacillin, Tazobactam Drug Combination
mesh term: Ticarcillin
mesh term: Ticarcillin-clavulanic acid