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EaRly impAct theraPy With Ceftazidime-avibactam Via rapID Diagnostics (RAPID)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05979545
Recruitment Status : Recruiting
First Posted : August 7, 2023
Last Update Posted : March 6, 2024
Sponsor:
Collaborators:
Pfizer
Biomerieux inc
Information provided by (Responsible Party):
National University of Singapore

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.


Condition or disease Intervention/treatment Phase
Blood Stream Infections Ventilator Associated Pneumonia Healthcare Associated Infection Carbapenem-Resistant Enterobacteriaceae Infection Hospital-acquired Pneumonia Diagnostic Test: Rapid Diagnostics Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1900 participants
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.
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : December 12, 2023
Estimated Primary Completion Date : October 31, 2026
Estimated Study Completion Date : December 31, 2026


Arm Intervention/treatment
Active Comparator: Intervention
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.
Diagnostic Test: Rapid Diagnostics
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.
Other Names:
  • BioFire FilmArray BCID2
  • BioFire FilmArray Pneumonia Plus Panel
  • BioFire FilmArray Pneumonia Panel

No Intervention: Control
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.



Primary Outcome Measures :
  1. 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 ]
    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 :
  1. Clinical response [ Time Frame: Day 7 and Day 14 post index culture ]
    Clinical response at Day 7 and Day 14 post index culture, as determined retrospectively by an adjudication committee

  2. All-cause mortality [ Time Frame: Day 14, Day 28, and Day 60 post index culture ]
    All-cause mortality at Day 14, Day 28, and Day 60 post index culture

  3. Functional outcome [ Time Frame: Day 14, Day 28 and Day 60 from collection of index culture ]
    Functional outcome at Day 14, Day 28 and Day 60 from collection of index culture

  4. Composite outcome [ Time Frame: Day 28 from index microbiology culture sample ]
    Composite outcome measure defined by Desirability of Outcome Ranking (DOOR) at Day 28 from index culture sample

  5. Implementation cost-Health Economics [ Time Frame: 60 days since enrolment ]
    Hospital and ICU level length of stay in the 60 days from randomisation


Other Outcome Measures:
  1. Genomics studies [ Time Frame: Day 0 ]
    Genotype of the infection causing bacterial isolate, as available through whole genome sequencing



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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,
  2. 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:

  1. Refractory shock or comorbid condition such that patient not expected to survive more than 48 hours; OR,
  2. where the bloodstream infection is thought to be related to a vascular catheter and the catheter is unable to be removed; OR,
  3. treatment is not with the intent to cure the infection; OR,
  4. patient is incarcerated in a correctional facility; OR,
  5. patients previously randomised in this trial within the last 60 days.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05979545


Contacts
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Contact: Kithalakshmi Vignesvaran 90300178 kitha@nus.edu.sg

Locations
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Malaysia
University Malaya Medical Centre Not yet recruiting
Kuala Lumpur, Malaysia, 50603
Contact: Norhabibah       nhabibahmohd11@gmail.com   
Principal Investigator: Helmi Sulaiman, Dr         
Sub-Investigator: Ong Hang Cheng, Dr         
Taiwan
Taichung Veterans General Hospital Recruiting
Taichung, Xitun District, Taiwan, 1650
Contact: Ying-Lan Li       yinglanli.vghtc@gmail.com   
Principal Investigator: Po-Yu Liu, Dr         
Sub-Investigator: Chien-Hao Tseng, Dr         
Kaohsiung Medical University Hospital Not yet recruiting
Kaohsiung, Taiwan
Contact: Hannah Yan-Zhen Hsu       hannah.hsu530@gmail.com   
Principal Investigator: Po-Liang Lu, Prof         
Sub-Investigator: Shang-yi Lin, Dr         
Sub-Investigator: Ya-Ting Chang, Dr         
Thailand
Sunpasitthiprasong Hospital Not yet recruiting
Ubon Ratchathani, Thailand, 34000
Contact: Sornsuda Setaphan, Ms       Sornsuda@tropmedres.ac   
Principal Investigator: Suwatthiya Kitsaran, Dr         
Sub-Investigator: Chamnan Parinya, Dr         
Sponsors and Collaborators
National University of Singapore
Pfizer
Biomerieux inc
Investigators
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Principal Investigator: David Paterson, Professor National University of Singapore
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Responsible Party: National University of Singapore
ClinicalTrials.gov Identifier: NCT05979545    
Other Study ID Numbers: ADVANCE-ID 22-002
23-0135 ( Other Grant/Funding Number: PFIZER INC )
225457/Z/22/Z ( Other Grant/Funding Number: Wellcome Trust )
20535 ( Other Identifier: BioMerieux )
First Posted: August 7, 2023    Key Record Dates
Last Update Posted: March 6, 2024
Last Verified: March 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National University of Singapore:
rapid diagnostics
ceftazidime-avibactam
carbapenemase producing Enterobacterales
hospital-acquired
MDR
AMR
ASP
CRE
BCID2
PN Plus
Additional relevant MeSH terms:
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Infections
Communicable Diseases
Pneumonia
Pneumonia, Ventilator-Associated
Healthcare-Associated Pneumonia
Sepsis
Cross Infection
Enterobacteriaceae Infections
Disease Attributes
Pathologic Processes
Respiratory Tract Infections
Lung Diseases
Respiratory Tract Diseases
Iatrogenic Disease
Systemic Inflammatory Response Syndrome
Inflammation
Gram-Negative Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses