EaRly impAct theraPy With Ceftazidime-avibactam Via rapID Diagnostics

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)

Overview

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.

Interventions

• 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 prescri

Primary outcome measures

• 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]

Secondary outcome measures (5)

• Clinical response [Time frame: Day 7 and Day 14 post index culture]
• All-cause mortality [Time frame: Day 14, Day 28, and Day 60 post index culture]
• Functional outcome [Time frame: Day 14, Day 28 and Day 60 from collection of index culture]
• Composite outcome [Time frame: Day 28 from index microbiology culture sample]
• Implementation cost-Health Economics [Time frame: 60 days since enrolment]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Taiwan · 2 centers

• Taichung Veterans General Hospital — Taichung
• Kaohsiung Medical University Hospital — Kaohsiung City

Malaysia · 1 center

• University Malaya Medical Centre — Kuala Lumpur

Thailand · 1 center

• Sunpasitthiprasong Hospital — Ubon Ratchathani

Identifiers

NCT: NCT05979545 · ADVANCE-ID 22-002 · 23-0135 · 225457/Z/22/Z · 20535

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗