xml: <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/NCT06035055</url>
    </required_header>
    <id_info>
      <org_study_id>U1111-1295-4030</org_study_id>
      <secondary_id>CT-2023-CTN-00033-1-v1</secondary_id>
      <nct_id>NCT06035055</nct_id>
    </id_info>
    <brief_title>Ceftolozane/Tazobactam Continuous Infusion for Infective Exacerbations of Cystic Fibrosis and Bronchiectasis</brief_title>
    <acronym>CERTAIN</acronym>
    <official_title>The Feasibility of Ceftolozane/Tazobactam Continuous Infusion for Exacerbations of Cystic Fibrosis and Bronchiectasis Treated in an Outpatient Parenteral Antibiotic Therapy (OPAT) Setting</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Sunshine Coast Hospital and Health Service</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>The Prince Charles Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Mater</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Sunshine Coast Hospital and Health Service</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>Yes</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        The goal of this clinical trial is to assess the feasibility of ceftolozane/tazobactam (C/T)&#xD;
        administered on an outpatient parenteral antibiotic therapy programme to patients with a&#xD;
        current infective exacerbation of bronchiectasis or cystic fibrosis related to pseudomonas&#xD;
        aeruginosa or burkholderia cepacia spp. organisms. The main question[s] it aims to answer&#xD;
        are:&#xD;
  &#xD;
          -  Is C/T effective, safe, well-tolerated and able to induce clinical and microbiologic&#xD;
             response?&#xD;
  &#xD;
          -  What are mechanisms of antimicrobial resistance are induced by administration of C/T?&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        For patients with cystic fibrosis (CF) and non-CF bronchiectasis, chronic airway infection&#xD;
        with Gram-negative organisms such as Pseudomonas aeruginosa and Burkholderia cepacia complex&#xD;
        species (BCC) is highly challenging to treat and associated with significant morbidity and&#xD;
        mortality. These organisms are naturally resistant towards many antibiotic classes, limiting&#xD;
        the available arsenal of effective antibiotics for their treatment and eradication.&#xD;
        Therefore, there is a pressing need for new antimicrobial therapy options for infective&#xD;
        exacerbations associated with these organisms.&#xD;
  &#xD;
        There are clear logistical and financial benefits for acute infective exacerbations of CF and&#xD;
        non-CF bronchiectasis to be managed on OPAT programs. Many acute infective exacerbations can&#xD;
        be safely managed in this way, and a substantial body of evidence supports non-inferiority of&#xD;
        OPAT compared with inpatient care. From a logistical perspective, feasibility of OPAT&#xD;
        programs is greatly improved by antibiotics being infused over a 24-hour period rather than&#xD;
        via bolus several times per day. Unfortunately, many mainstay anti-pseudomonal and&#xD;
        anti-Burkholderia antibiotics (including meropenem, imipenem and ceftazidime) are not stable&#xD;
        for 24 hours at room/body temperature therefore are unsuitable for use on OPAT.&#xD;
  &#xD;
        This study aims to assess viability of ceftolozane/tazobactam (C/T) administered via OPAT in&#xD;
        adult patients with exacerbations of CF or non-CF bronchiectasis. Secondary aims are to&#xD;
        describe clinical outcomes of patients receiving C/T, tolerability of C/T, relative sputum&#xD;
        bacterial load throughout treatment and assess development of resistance to C/T and other&#xD;
        antibiotics. We aim to recruit 30 patients, colonized with either pseudomonas aeruginosa or&#xD;
        burkholderia cepacia complex, with a current infectious exacerbation requiring intravenous&#xD;
        antibiotic treatment. We propose to administer C/T via infusion for 10-14 days with review at&#xD;
        day 0-3, 5-7 and 10-14. Blood testing, sputum testing, lung function testing, administration&#xD;
        of CF- and bronchiectasis-specific questionnaires and adverse event reporting will be carried&#xD;
        out at these times. Serum levels of C/T will be monitored using a validated assay. Clinical&#xD;
        review at day 28-42 will be carried out to assess for recrudescence of symptoms and further&#xD;
        need for antibiotics and a follow-up phone call will be made at 3 months to assess whether&#xD;
        any further antibiotics were needed for new/recrudescent symptoms of infection.&#xD;
  &#xD;
        We expect to find that C/T is safe, well-tolerated and effective in treating infective&#xD;
        exacerbations of bronchiectasis in OPAT settings. We expect to find that bacterial density in&#xD;
        sputum samples reduces over the course of treatment, and that development of antimicrobial&#xD;
        resistance is minimal.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">January 2024</completion_date>
    <primary_completion_date type="Anticipated">October 2023</primary_completion_date>
    <phase>Phase 4</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <intervention_model_description>30 patients will be recruited and will receive the study intervention.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>The feasibility of the use of ceftolozane/tazobactam given via continuous infusion in an OPAT setting for the treatment of acute exacerbations of CF and bronchiectasis.</measure>
      <time_frame>Day 0 to day 90 post commencement of intervention.</time_frame>
      <description>The feasibility of the use of ceftolozane/tazobactam given via continuous infusion in an OPAT setting for the treatment of acute exacerbations of CF and bronchiectasis will be assessed. Feasibility will be determined as a composite of clinical response (as assessed by disease-specific questionnaires, serum inflammatory marker monitoring and spirometry in the case of patients with cystic fibrosis), adverse events and report of relapse of respiratory infection at 3 months.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Safety and tolerability</measure>
      <time_frame>Day 0 to day 90 post commencement of intervention.</time_frame>
      <description>Safety and tolerability of continuous infusion ceftolozane/tazobactam. Ceftolozane/tazobactam has a very similar adverse event (AE) profile to other broad spectrum intravenous antibiotics, e.g. piperacillin/tazobactam and meropenem. Possible symptomatic AE's include: nausea, diarrhoea, headache, vomiting, constipation, insomnia, rash and fever. These will be assessed direct questioning of participants at the time of research visits, by clinical examination and and by participants self-reporting symptoms of concern to the research team any time during or after their course of ceftolozane/tazobactam. Possible laboratory abnormalities include: liver function test derangement and acute kidney injury. These will be monitored by regular blood tests during and after the course of ceftolozane/tazobactam.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Relative bacterial load</measure>
      <time_frame>Day 0-1, Day 5-7, Day 10-14, Day 28-42</time_frame>
      <description>To describe relative bacterial load over the course of ceftolozane/tazobactam treatment as assessed by quantitative PCR (qPCR) on sputa.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>In vitro antimicrobial susceptibility/resistance</measure>
      <time_frame>Day 0-1, Day 5-7, Day 10-14, Day 28-42</time_frame>
      <description>To describe in vitro antimicrobial susceptibility of airway pathogens to ceftolozane/tazobactam and other anti-pseudomonal/anti-Burkholderia antibiotics over the course of ceftolozane/tazobactam treatment. This will be determined by a composite outcome of antimicrobial susceptibility testing, whole-genome sequencing (WGS), culturomic sequencing, and bioinformatic analysis.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">30</enrollment>
    <condition>Bronchiectasis</condition>
    <condition>Cystic Fibrosis</condition>
    <condition>Pseudomonas Aeruginosa</condition>
    <condition>Burkholderia Cepacia Infection</condition>
    <arm_group>
      <arm_group_label>Ceftolozane/tazobactam 9g infusion</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>9g ceftolozane/tazobactam in 240 millilitres 0.9% sodium chloride IV infusion given over 24 hours for 10-14 days</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Ceftolozane/tazobactam</intervention_name>
      <description>9g ceftolozane/tazobactam in 240 millilitres 0.9% sodium chloride IV infusion given over 24 hours for 10-14 days</description>
      <arm_group_label>Ceftolozane/tazobactam 9g infusion</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Diagnosis of CF or non-CF bronchiectasis&#xD;
  &#xD;
            -  Colonised with P. aeruginosa or BCC species&#xD;
  &#xD;
            -  Current infectious exacerbation requiring treatment with intravenous antibiotics&#xD;
  &#xD;
            -  Productive of sputum&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Unable to consent&#xD;
  &#xD;
            -  Active pregnancy (as confirmed by urine beta-HCG)&#xD;
  &#xD;
            -  Not appropriate for OPAT (as determined by treating clinician)&#xD;
  &#xD;
            -  Estimated Creatinine Clearance &lt; 50 millilitres/min&#xD;
  &#xD;
            -  History of hypersensitivity reaction to piperacillin/tazobactam or members of the&#xD;
               cephalosporin class of antibiotics&#xD;
  &#xD;
            -  Unable to expectorate&#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>Julia J Bashford, BSc, MBBS</last_name>
      <role>Principal Investigator</role>
      <affiliation>Sunshine Coast University Hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Andrew Burke, MBBS</last_name>
      <role>Principal Investigator</role>
      <affiliation>The Prince Charles Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Julia J Bashford, MBBS FRACP</last_name>
      <phone>+61752021071</phone>
      <email>julia.bashford@health.qld.gov.au</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Andrew Burke, MBBS FRACP</last_name>
      <email>Andrew.Burke@health.qld.gov.au</email>
    </overall_contact_backup>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 6, 2023</study_first_submitted>
    <study_first_submitted_qc>September 6, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 13, 2023</study_first_posted>
    <last_update_submitted>September 6, 2023</last_update_submitted>
    <last_update_submitted_qc>September 6, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Sunshine Coast Hospital and Health Service</investigator_affiliation>
      <investigator_full_name>Julia Bashford</investigator_full_name>
      <investigator_title>Dr</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Burkholderia Infections</mesh_term>
      <mesh_term>Cystic Fibrosis</mesh_term>
      <mesh_term>Bronchiectasis</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>Ceftolozane</mesh_term>
      <mesh_term>Ceftolozane, tazobactam drug combination</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>Only de-identified, line-by-line data will be be provided to researchers who provide a sound proposal to allow for meta-analyses requiring individual participant data (IPD). Data will be available immediately following publication, with there being no pre-determined end date on IPD sharing.</ipd_description>
      <ipd_time_frame>Data will be available immediately following publication, with there being no pre-determined end date on IPD sharing.</ipd_time_frame>
      <ipd_access_criteria>Data will be available only to researchers who provide a sound proposal e.g. planned systematic review and meta-analysis.</ipd_access_criteria>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06035055
  org study id: U1111-1295-4030
  secondary id: CT-2023-CTN-00033-1-v1
  nct id: NCT06035055
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: Yes
  The goal of this clinical trial is to assess the feasibility of ceftolozane/tazobactam (C/T)
        administered on an outpatient parenteral antibiotic therapy programme to patients with a
        current infective exacerbation of bronchiectasis or cystic fibrosis related to pseudomonas
        aeruginosa or burkholderia cepacia spp. organisms. The main question[s] it aims to answer
        are:
  
          -  Is C/T effective, safe, well-tolerated and able to induce clinical and microbiologic
             response?
  
          -  What are mechanisms of antimicrobial resistance are induced by administration of C/T?
  For patients with cystic fibrosis (CF) and non-CF bronchiectasis, chronic airway infection
        with Gram-negative organisms such as Pseudomonas aeruginosa and Burkholderia cepacia complex
        species (BCC) is highly challenging to treat and associated with significant morbidity and
        mortality. These organisms are naturally resistant towards many antibiotic classes, limiting
        the available arsenal of effective antibiotics for their treatment and eradication.
        Therefore, there is a pressing need for new antimicrobial therapy options for infective
        exacerbations associated with these organisms.
  
        There are clear logistical and financial benefits for acute infective exacerbations of CF and
        non-CF bronchiectasis to be managed on OPAT programs. Many acute infective exacerbations can
        be safely managed in this way, and a substantial body of evidence supports non-inferiority of
        OPAT compared with inpatient care. From a logistical perspective, feasibility of OPAT
        programs is greatly improved by antibiotics being infused over a 24-hour period rather than
        via bolus several times per day. Unfortunately, many mainstay anti-pseudomonal and
        anti-Burkholderia antibiotics (including meropenem, imipenem and ceftazidime) are not stable
        for 24 hours at room/body temperature therefore are unsuitable for use on OPAT.
  
        This study aims to assess viability of ceftolozane/tazobactam (C/T) administered via OPAT in
        adult patients with exacerbations of CF or non-CF bronchiectasis. Secondary aims are to
        describe clinical outcomes of patients receiving C/T, tolerability of C/T, relative sputum
        bacterial load throughout treatment and assess development of resistance to C/T and other
        antibiotics. We aim to recruit 30 patients, colonized with either pseudomonas aeruginosa or
        burkholderia cepacia complex, with a current infectious exacerbation requiring intravenous
        antibiotic treatment. We propose to administer C/T via infusion for 10-14 days with review at
        day 0-3, 5-7 and 10-14. Blood testing, sputum testing, lung function testing, administration
        of CF- and bronchiectasis-specific questionnaires and adverse event reporting will be carried
        out at these times. Serum levels of C/T will be monitored using a validated assay. Clinical
        review at day 28-42 will be carried out to assess for recrudescence of symptoms and further
        need for antibiotics and a follow-up phone call will be made at 3 months to assess whether
        any further antibiotics were needed for new/recrudescent symptoms of infection.
  
        We expect to find that C/T is safe, well-tolerated and effective in treating infective
        exacerbations of bronchiectasis in OPAT settings. We expect to find that bacterial density in
        sputum samples reduces over the course of treatment, and that development of antimicrobial
        resistance is minimal.
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: 30 patients will be recruited and will receive the study intervention.
  primary purpose: Treatment
  masking: None (Open Label)
  measure: The feasibility of the use of ceftolozane/tazobactam given via continuous infusion in an OPAT setting for the treatment of acute exacerbations of CF and bronchiectasis.
  time frame: Day 0 to day 90 post commencement of intervention.
  description: The feasibility of the use of ceftolozane/tazobactam given via continuous infusion in an OPAT setting for the treatment of acute exacerbations of CF and bronchiectasis will be assessed. Feasibility will be determined as a composite of clinical response (as assessed by disease-specific questionnaires, serum inflammatory marker monitoring and spirometry in the case of patients with cystic fibrosis), adverse events and report of relapse of respiratory infection at 3 months.
  measure: Safety and tolerability
  time frame: Day 0 to day 90 post commencement of intervention.
  description: Safety and tolerability of continuous infusion ceftolozane/tazobactam. Ceftolozane/tazobactam has a very similar adverse event (AE) profile to other broad spectrum intravenous antibiotics, e.g. piperacillin/tazobactam and meropenem. Possible symptomatic AE's include: nausea, diarrhoea, headache, vomiting, constipation, insomnia, rash and fever. These will be assessed direct questioning of participants at the time of research visits, by clinical examination and and by participants self-reporting symptoms of concern to the research team any time during or after their course of ceftolozane/tazobactam. Possible laboratory abnormalities include: liver function test derangement and acute kidney injury. These will be monitored by regular blood tests during and after the course of ceftolozane/tazobactam.
  measure: Relative bacterial load
  time frame: Day 0-1, Day 5-7, Day 10-14, Day 28-42
  description: To describe relative bacterial load over the course of ceftolozane/tazobactam treatment as assessed by quantitative PCR (qPCR) on sputa.
  measure: In vitro antimicrobial susceptibility/resistance
  time frame: Day 0-1, Day 5-7, Day 10-14, Day 28-42
  description: To describe in vitro antimicrobial susceptibility of airway pathogens to ceftolozane/tazobactam and other anti-pseudomonal/anti-Burkholderia antibiotics over the course of ceftolozane/tazobactam treatment. This will be determined by a composite outcome of antimicrobial susceptibility testing, whole-genome sequencing (WGS), culturomic sequencing, and bioinformatic analysis.
  arm group label: Ceftolozane/tazobactam 9g infusion
  arm group type: Experimental
  description: 9g ceftolozane/tazobactam in 240 millilitres 0.9% sodium chloride IV infusion given over 24 hours for 10-14 days
  intervention type: Drug
  intervention name: Ceftolozane/tazobactam
  description: 9g ceftolozane/tazobactam in 240 millilitres 0.9% sodium chloride IV infusion given over 24 hours for 10-14 days
  arm group label: Ceftolozane/tazobactam 9g infusion
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Julia J Bashford, BSc, MBBS
  role: Principal Investigator
  affiliation: Sunshine Coast University Hospital
  last name: Andrew Burke, MBBS
  role: Principal Investigator
  affiliation: The Prince Charles Hospital
  last name: Julia J Bashford, MBBS FRACP
  phone: +61752021071
  email: julia.bashford@health.qld.gov.au
  last name: Andrew Burke, MBBS FRACP
  email: Andrew.Burke@health.qld.gov.au
  responsible party type: Principal Investigator
  investigator affiliation: Sunshine Coast Hospital and Health Service
  investigator full name: Julia Bashford
  investigator title: Dr
  mesh term: Burkholderia Infections
  mesh term: Cystic Fibrosis
  mesh term: Bronchiectasis
  mesh term: Fibrosis
  mesh term: Tazobactam
  mesh term: Ceftolozane
  mesh term: Ceftolozane, tazobactam drug combination
  sharing ipd: Yes
  ipd description: Only de-identified, line-by-line data will be be provided to researchers who provide a sound proposal to allow for meta-analyses requiring individual participant data (IPD). Data will be available immediately following publication, with there being no pre-determined end date on IPD sharing.
  ipd time frame: Data will be available immediately following publication, with there being no pre-determined end date on IPD sharing.
  ipd access criteria: Data will be available only to researchers who provide a sound proposal e.g. planned systematic review and meta-analysis.