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/NCT05979545</url>
    </required_header>
    <id_info>
      <org_study_id>ADVANCE-ID 22-002</org_study_id>
      <secondary_id>23-0135</secondary_id>
      <secondary_id>225457/Z/22/Z</secondary_id>
      <secondary_id>20535</secondary_id>
      <nct_id>NCT05979545</nct_id>
    </id_info>
    <brief_title>EaRly impAct theraPy With Ceftazidime-avibactam Via rapID Diagnostics Versus Standard of Care Antibiotics and Diagnostics in Patients With Bloodstream Infection, Hospital-acquired Pneumonia or Ventilator-associated Pneumonia Due to Pseudomonas Aeruginosa or Carbapenemase Producing Enterobacterales</brief_title>
    <acronym>RAPID</acronym>
    <official_title>EaRly impAct theraPy With Ceftazidime-avibactam Via rapID Diagnostics Versus Standard of Care Antibiotics and Diagnostics in Patients With Bloodstream Infection, Hospital-acquired Pneumonia or Ventilator-associated Pneumonia Due to Pseudomonas Aeruginosa or Carbapenemase Producing Enterobacterales (RAPID)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>National University of Singapore</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Pfizer</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
      <collaborator>
        <agency>Biomerieux inc</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>National University of Singapore</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The goal of this clinical trial is to propose a seamless intervention linking rapid bacterial&#xD;
        isolate identification and antibiotic resistance gene detection and targeted antibiotic&#xD;
        prescription to minimise time between infection onset and appropriate treatment in patients&#xD;
        with Pseudomonas aeruginosa or carbapenemase producing Enterobacterales infections. This is&#xD;
        an investigator initiated trial.&#xD;
  &#xD;
        The primary hypothesis is that these interventions will lead to improved clinical outcomes&#xD;
        amongst patients with hospital-acquired bloodstream infection, hospital-acquired pneumonia or&#xD;
        ventilator-associated pneumonia due to carbapenem non-susceptible Pseudomonas aeruginosa or&#xD;
        Enterobacterales, compared to standard antibiotic susceptibility testing.&#xD;
  &#xD;
        Patients will be randomised to either a control or intervention arm. Patients randomised to&#xD;
        the intervention arm will have relevant specimens analysed by rapid microbiological&#xD;
        diagnostics and will have early availability of ceftazidime-avibactam if appropriate.&#xD;
        Patients randomised to the control arm, will have samples analysed by clinical microbiology&#xD;
        laboratories using standard of care diagnostics. Antibiotics will be available to these&#xD;
        patients as per usual institutional practice.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is an open-label, multinational, randomised, superiority trial. Patients will be&#xD;
        randomised to control and intervention arms.&#xD;
  &#xD;
        Patients randomised to the intervention arm, will have the BioFire Blood Culture&#xD;
        Identification 2 Panel (BCID2) used for positive blood cultures and/or the BioFire FilmArray&#xD;
        Pneumonia or Pneumonia plus Panel for respiratory tract specimens if having hospital-acquired&#xD;
        pneumonia or ventilator-associated pneumonia. Standard of care diagnostics will also be used.&#xD;
        Antibiotic guidelines will be provided to clinicians to aid interpretation of test results&#xD;
        and treatment prescription. Ceftazidime-avibactam will be available for targeted use in&#xD;
        patients with Pseudomonas aeruginosa or carbapenemase producing Enterobacterales.&#xD;
  &#xD;
        Patients randomised to the control arm, will have samples analysed by clinical microbiology&#xD;
        laboratories using standard of care diagnostics. Antibiotics will be available to these&#xD;
        patients as per usual institutional practice.&#xD;
  &#xD;
        The main population that will be recruited in the study will be hospitalised patients with&#xD;
        bloodstream infections, hospital-acquired pneumonia or ventilator-associated pneumonia due to&#xD;
        Pseudomonas aeruginosa or carbapenemase producing Enterobacterales treated with&#xD;
        ceftazidime-avibactam, while the secondary population recruited will be those with multidrug&#xD;
        resistant (MDR) Gram-negative bacilli. The enrolment criteria are based on the US Centers for&#xD;
        Disease Control and Prevention criteria for healthcare-associated infection surveillance.&#xD;
  &#xD;
        Clinical and mortality outcomes will be assessed for 60 days post infection. The infection&#xD;
        causing bacterial isolates will be collected for genotypic description via whole genome&#xD;
        sequencing. The total target sample size is 1900 participants in the main population over 20&#xD;
        study sites.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 1, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2026</completion_date>
    <primary_completion_date type="Anticipated">October 31, 2026</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>
      <intervention_model_description>The primary aim is to quantify the combined effect of a PCR-based rapid microbiology diagnostic system and locally adapted antibiotic stewardship on patients with infections due to Pseudomonas aeruginosa or carbapenemase producing Enterobacterales. The combined effect of diagnostics and appropriate antibiotic is the primary focus in the RAPID trial as they are closely interlinked.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Composite endpoint of all-cause mortality and/or no improvement in SOFA score at Day 14 post index culture</measure>
      <time_frame>14 days post index culture</time_frame>
      <description>Patient has died within 14 days from collection of index microbiology culture from any cause or SOFA score has not improved at Day 14 compared with baseline score on day of collection of index microbiology culture</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Clinical response</measure>
      <time_frame>Day 7 and Day 14 post index culture</time_frame>
      <description>Clinical response at Day 7 and Day 14 post index culture, as determined retrospectively by an adjudication committee</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>All-cause mortality</measure>
      <time_frame>Day 14, Day 28, and Day 60 post index culture</time_frame>
      <description>All-cause mortality at Day 14, Day 28, and Day 60 post index culture</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Functional outcome</measure>
      <time_frame>Day 14, Day 28 and Day 60 from collection of index culture</time_frame>
      <description>Functional outcome at Day 14, Day 28 and Day 60 from collection of index culture</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Composite outcome</measure>
      <time_frame>Day 28 from index microbiology culture sample</time_frame>
      <description>Composite outcome measure defined by Desirability of Outcome Ranking (DOOR) at Day 28 from index culture sample</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Health Economics</measure>
      <time_frame>60 days since enrolment</time_frame>
      <description>To assess the implementation cost, we will capture hospital and ICU-level length of stay in the 60 days from randomisation</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Exploratory Outcome</measure>
      <time_frame>Day 0</time_frame>
      <description>Describe bacterial genotype of the infection causing bacterial isolate, as available through whole genome sequencing</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">1900</enrollment>
    <condition>Blood Stream Infections</condition>
    <condition>Ventilator Associated Pneumonia</condition>
    <condition>Healthcare Associated Infection</condition>
    <condition>Carbapenem-Resistant Enterobacteriaceae Infection</condition>
    <condition>Hospital-acquired Pneumonia</condition>
    <arm_group>
      <arm_group_label>Intervention</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Samples from patients randomised to the intervention arm will undergo the BioFire FilmArray systems. Patients will be then administered with the study drug, ceftazidime-avibactam when Pseudomonas aeruginosa or carbapenemase producing Enterobacterales detected.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control</arm_group_label>
      <arm_group_type>No Intervention</arm_group_type>
      <description>Patients randomised to the control arm, will have samples analysed by clinical microbiology laboratories using standard of care diagnostics. Antibiotics treatment will be administered as per usual institutional practice from hospital supplies.</description>
    </arm_group>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Rapid Diagnostics</intervention_name>
      <description>Patients randomised to the intervention arm, will have the BioFire Blood Culture Identification 2 Panel (BCID2) used for positive blood cultures and/or the BioFire FilmArray Pneumonia plus PanelPneumonia Panel or Pneumonia plus Panel for respiratory tract specimens if having hospital-acquired pneumonia or ventilator-associated pneumonia. Standard of care diagnostics will also be used. Antibiotic guidelines will be provided to clinicians to aid interpretation of test results and treatment prescription. Ceftazidime-avibactam will be available for targeted use in patients with Pseudomonas aeruginosa or carbapenemase producing Enterobacterales.</description>
      <arm_group_label>Intervention</arm_group_label>
      <other_name>BioFire FilmArray BCID2</other_name>
      <other_name>BioFire FilmArray Pneumonia Plus Panel</other_name>
      <other_name>BioFire FilmArray Pneumonia Panel</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. patient developed clinical symptoms compatible with bloodstream infection,&#xD;
               hospital-acquired or ventilator-associated pneumonia (hospital-acquired and&#xD;
               ventilator-associated pneumonia should fulfil US CDC NHSN criteria) AND,&#xD;
  &#xD;
            2. an appropriate specimen has been received by the participating laboratory - that is, a&#xD;
               blood culture bottle showing Gram negative bacilli or a respiratory sample collected&#xD;
               for clinical purposes showing Gram negative bacilli on Gram stain;&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Refractory shock or comorbid condition such that patient not expected to survive more&#xD;
               than 48 hours; OR,&#xD;
  &#xD;
            2. where the bloodstream infection is thought to be related to a vascular catheter and&#xD;
               the catheter is unable to be removed; OR,&#xD;
  &#xD;
            3. treatment is not with the intent to cure the infection; OR,&#xD;
  &#xD;
            4. patient is incarcerated in a correctional facility; OR,&#xD;
  &#xD;
            5. patients previously randomised in this trial within the last 60 days.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>N/A</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 31, 2023</study_first_submitted>
    <study_first_submitted_qc>July 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 7, 2023</study_first_posted>
    <last_update_submitted>July 31, 2023</last_update_submitted>
    <last_update_submitted_qc>July 31, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 7, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>rapid diagnostics</keyword>
    <keyword>ceftazidime-avibactam</keyword>
    <keyword>carbapenemase producing Enterobacterales</keyword>
    <keyword>hospital-acquired</keyword>
    <keyword>MDR</keyword>
    <keyword>AMR</keyword>
    <keyword>ASP</keyword>
    <keyword>CRE</keyword>
    <keyword>BCID2</keyword>
    <keyword>PN Plus</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Infections</mesh_term>
      <mesh_term>Communicable Diseases</mesh_term>
      <mesh_term>Pneumonia</mesh_term>
      <mesh_term>Pneumonia, Ventilator-Associated</mesh_term>
      <mesh_term>Sepsis</mesh_term>
      <mesh_term>Healthcare-Associated Pneumonia</mesh_term>
      <mesh_term>Cross Infection</mesh_term>
      <mesh_term>Enterobacteriaceae Infections</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </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/NCT05979545
  org study id: ADVANCE-ID 22-002
  secondary id: 23-0135
  secondary id: 225457/Z/22/Z
  secondary id: 20535
  nct id: NCT05979545
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this clinical trial is to propose a seamless intervention linking rapid bacterial
        isolate identification and antibiotic resistance gene detection and targeted antibiotic
        prescription to minimise time between infection onset and appropriate treatment in patients
        with Pseudomonas aeruginosa or carbapenemase producing Enterobacterales infections. This is
        an investigator initiated trial.
  
        The primary hypothesis is that these interventions will lead to improved clinical outcomes
        amongst patients with hospital-acquired bloodstream infection, hospital-acquired pneumonia or
        ventilator-associated pneumonia due to carbapenem non-susceptible Pseudomonas aeruginosa or
        Enterobacterales, compared to standard antibiotic susceptibility testing.
  
        Patients will be randomised to either a control or intervention arm. Patients randomised to
        the intervention arm will have relevant specimens analysed by rapid microbiological
        diagnostics and will have early availability of ceftazidime-avibactam if appropriate.
        Patients randomised to the control arm, will have samples analysed by clinical microbiology
        laboratories using standard of care diagnostics. Antibiotics will be available to these
        patients as per usual institutional practice.
  This is an open-label, multinational, randomised, superiority trial. Patients will be
        randomised to control and intervention arms.
  
        Patients randomised to the intervention arm, will have the BioFire Blood Culture
        Identification 2 Panel (BCID2) used for positive blood cultures and/or the BioFire FilmArray
        Pneumonia or Pneumonia plus Panel for respiratory tract specimens if having hospital-acquired
        pneumonia or ventilator-associated pneumonia. Standard of care diagnostics will also be used.
        Antibiotic guidelines will be provided to clinicians to aid interpretation of test results
        and treatment prescription. Ceftazidime-avibactam will be available for targeted use in
        patients with Pseudomonas aeruginosa or carbapenemase producing Enterobacterales.
  
        Patients randomised to the control arm, will have samples analysed by clinical microbiology
        laboratories using standard of care diagnostics. Antibiotics will be available to these
        patients as per usual institutional practice.
  
        The main population that will be recruited in the study will be hospitalised patients with
        bloodstream infections, hospital-acquired pneumonia or ventilator-associated pneumonia due to
        Pseudomonas aeruginosa or carbapenemase producing Enterobacterales treated with
        ceftazidime-avibactam, while the secondary population recruited will be those with multidrug
        resistant (MDR) Gram-negative bacilli. The enrolment criteria are based on the US Centers for
        Disease Control and Prevention criteria for healthcare-associated infection surveillance.
  
        Clinical and mortality outcomes will be assessed for 60 days post infection. The infection
        causing bacterial isolates will be collected for genotypic description via whole genome
        sequencing. The total target sample size is 1900 participants in the main population over 20
        study sites.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: The primary aim is to quantify the combined effect of a PCR-based rapid microbiology diagnostic system and locally adapted antibiotic stewardship on patients with infections due to Pseudomonas aeruginosa or carbapenemase producing Enterobacterales. The combined effect of diagnostics and appropriate antibiotic is the primary focus in the RAPID trial as they are closely interlinked.
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Composite endpoint of all-cause mortality and/or no improvement in SOFA score at Day 14 post index culture
  time frame: 14 days post index culture
  description: Patient has died within 14 days from collection of index microbiology culture from any cause or SOFA score has not improved at Day 14 compared with baseline score on day of collection of index microbiology culture
  measure: Clinical response
  time frame: Day 7 and Day 14 post index culture
  description: Clinical response at Day 7 and Day 14 post index culture, as determined retrospectively by an adjudication committee
  measure: All-cause mortality
  time frame: Day 14, Day 28, and Day 60 post index culture
  description: All-cause mortality at Day 14, Day 28, and Day 60 post index culture
  measure: Functional outcome
  time frame: Day 14, Day 28 and Day 60 from collection of index culture
  description: Functional outcome at Day 14, Day 28 and Day 60 from collection of index culture
  measure: Composite outcome
  time frame: Day 28 from index microbiology culture sample
  description: Composite outcome measure defined by Desirability of Outcome Ranking (DOOR) at Day 28 from index culture sample
  measure: Health Economics
  time frame: 60 days since enrolment
  description: To assess the implementation cost, we will capture hospital and ICU-level length of stay in the 60 days from randomisation
  measure: Exploratory Outcome
  time frame: Day 0
  description: Describe bacterial genotype of the infection causing bacterial isolate, as available through whole genome sequencing
  arm group label: Intervention
  arm group type: Active Comparator
  description: Samples from patients randomised to the intervention arm will undergo the BioFire FilmArray systems. Patients will be then administered with the study drug, ceftazidime-avibactam when Pseudomonas aeruginosa or carbapenemase producing Enterobacterales detected.
  arm group label: Control
  arm group type: No Intervention
  description: Patients randomised to the control arm, will have samples analysed by clinical microbiology laboratories using standard of care diagnostics. Antibiotics treatment will be administered as per usual institutional practice from hospital supplies.
  intervention type: Diagnostic Test
  intervention name: Rapid Diagnostics
  description: Patients randomised to the intervention arm, will have the BioFire Blood Culture Identification 2 Panel (BCID2) used for positive blood cultures and/or the BioFire FilmArray Pneumonia plus PanelPneumonia Panel or Pneumonia plus Panel for respiratory tract specimens if having hospital-acquired pneumonia or ventilator-associated pneumonia. Standard of care diagnostics will also be used. Antibiotic guidelines will be provided to clinicians to aid interpretation of test results and treatment prescription. Ceftazidime-avibactam will be available for targeted use in patients with Pseudomonas aeruginosa or carbapenemase producing Enterobacterales.
  arm group label: Intervention
  other name: BioFire FilmArray BCID2
  other name: BioFire FilmArray Pneumonia Plus Panel
  other name: BioFire FilmArray Pneumonia Panel
  criteria: 
  gender: All
  minimum age: N/A
  maximum age: N/A
  healthy volunteers: No
  responsible party type: Sponsor
  mesh term: Infections
  mesh term: Communicable Diseases
  mesh term: Pneumonia
  mesh term: Pneumonia, Ventilator-Associated
  mesh term: Sepsis
  mesh term: Healthcare-Associated Pneumonia
  mesh term: Cross Infection
  mesh term: Enterobacteriaceae Infections
  sharing ipd: Undecided