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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)

Primary Purpose

Blood Stream Infections, Ventilator Associated Pneumonia, Healthcare Associated Infection

Status
Not yet recruiting
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Rapid Diagnostics
Sponsored by
National University of Singapore
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Blood Stream Infections focused on measuring rapid diagnostics, ceftazidime-avibactam, carbapenemase producing Enterobacterales, hospital-acquired, MDR, AMR, ASP, CRE, BCID2, PN Plus

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: patient developed clinical symptoms compatible with bloodstream infection, hospital-acquired or ventilator-associated pneumonia (hospital-acquired and ventilator-associated pneumonia should fulfil US CDC NHSN criteria) AND, an appropriate specimen has been received by the participating laboratory - that is, a blood culture bottle showing Gram negative bacilli or a respiratory sample collected for clinical purposes showing Gram negative bacilli on Gram stain; Exclusion Criteria: Refractory shock or comorbid condition such that patient not expected to survive more than 48 hours; OR, where the bloodstream infection is thought to be related to a vascular catheter and the catheter is unable to be removed; OR, treatment is not with the intent to cure the infection; OR, patient is incarcerated in a correctional facility; OR, patients previously randomised in this trial within the last 60 days.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    No Intervention

    Arm Label

    Intervention

    Control

    Arm 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.

    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.

    Outcomes

    Primary Outcome Measures

    Composite endpoint of all-cause mortality and/or no improvement in SOFA score at Day 14 post index culture
    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

    Secondary Outcome Measures

    Clinical response
    Clinical response at Day 7 and Day 14 post index culture, as determined retrospectively by an adjudication committee
    All-cause mortality
    All-cause mortality at Day 14, Day 28, and Day 60 post index culture
    Functional outcome
    Functional outcome at Day 14, Day 28 and Day 60 from collection of index culture
    Composite outcome
    Composite outcome measure defined by Desirability of Outcome Ranking (DOOR) at Day 28 from index culture sample
    Health Economics
    To assess the implementation cost, we will capture hospital and ICU-level length of stay in the 60 days from randomisation

    Full Information

    First Posted
    July 31, 2023
    Last Updated
    July 31, 2023
    Sponsor
    National University of Singapore
    Collaborators
    Pfizer, Biomerieux inc
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05979545
    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
    Acronym
    RAPID
    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)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 1, 2023 (Anticipated)
    Primary Completion Date
    October 31, 2026 (Anticipated)
    Study Completion Date
    December 31, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    National University of Singapore
    Collaborators
    Pfizer, Biomerieux inc

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    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.
    Detailed Description
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Blood Stream Infections, Ventilator Associated Pneumonia, Healthcare Associated Infection, Carbapenem-Resistant Enterobacteriaceae Infection, Hospital-acquired Pneumonia
    Keywords
    rapid diagnostics, ceftazidime-avibactam, carbapenemase producing Enterobacterales, hospital-acquired, MDR, AMR, ASP, CRE, BCID2, PN Plus

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 4
    Interventional Study Model
    Parallel Assignment
    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.
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    1900 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Intervention
    Arm Type
    Active Comparator
    Arm 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 Title
    Control
    Arm Type
    No Intervention
    Arm 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(s)
    Rapid Diagnostics
    Other Intervention Name(s)
    BioFire FilmArray BCID2, BioFire FilmArray Pneumonia Plus Panel, BioFire FilmArray Pneumonia Panel
    Intervention 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.
    Primary Outcome Measure Information:
    Title
    Composite endpoint of all-cause mortality and/or no improvement in SOFA score at Day 14 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
    Time Frame
    14 days post index culture
    Secondary Outcome Measure Information:
    Title
    Clinical response
    Description
    Clinical response at Day 7 and Day 14 post index culture, as determined retrospectively by an adjudication committee
    Time Frame
    Day 7 and Day 14 post index culture
    Title
    All-cause mortality
    Description
    All-cause mortality at Day 14, Day 28, and Day 60 post index culture
    Time Frame
    Day 14, Day 28, and Day 60 post index culture
    Title
    Functional outcome
    Description
    Functional outcome at Day 14, Day 28 and Day 60 from collection of index culture
    Time Frame
    Day 14, Day 28 and Day 60 from collection of index culture
    Title
    Composite outcome
    Description
    Composite outcome measure defined by Desirability of Outcome Ranking (DOOR) at Day 28 from index culture sample
    Time Frame
    Day 28 from index microbiology culture sample
    Title
    Health Economics
    Description
    To assess the implementation cost, we will capture hospital and ICU-level length of stay in the 60 days from randomisation
    Time Frame
    60 days since enrolment
    Other Pre-specified Outcome Measures:
    Title
    Exploratory Outcome
    Description
    Describe bacterial genotype of the infection causing bacterial isolate, as available through whole genome sequencing
    Time Frame
    Day 0

    10. Eligibility

    Sex
    All
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: patient developed clinical symptoms compatible with bloodstream infection, hospital-acquired or ventilator-associated pneumonia (hospital-acquired and ventilator-associated pneumonia should fulfil US CDC NHSN criteria) AND, an appropriate specimen has been received by the participating laboratory - that is, a blood culture bottle showing Gram negative bacilli or a respiratory sample collected for clinical purposes showing Gram negative bacilli on Gram stain; Exclusion Criteria: Refractory shock or comorbid condition such that patient not expected to survive more than 48 hours; OR, where the bloodstream infection is thought to be related to a vascular catheter and the catheter is unable to be removed; OR, treatment is not with the intent to cure the infection; OR, patient is incarcerated in a correctional facility; OR, patients previously randomised in this trial within the last 60 days.

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided

    Learn more about this trial

    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

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