EaRly impAct theraPy With Ceftazidime-avibactam Via rapID Diagnostics

Condition(s) studied

Investigational drug(s) / intervention(s)

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. Rapid diagnostic testing must be initiated as soon as Gram-negative bacilli is detected on Gram stain, and appropriate antibiotic must be administered according to predefined antibiotic stewardship guidelines within 24 hours of the Gram stain being performed on the index respiratory or blood culture specimen, that defined entry into the trial. 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.

Study summary

RAPID is an investigator initiated Phase 4, multinational, multicentre, open-label, randomised controlled superiority trial evaluating the clinical impact of rapid microbiological diagnostics combined with antimicrobial stewardship and early targeted antibiotic therapy compared with standard-of-care diagnostics and antibiotics.

Hospitalised adult patients with bloodstream infections, hospital-acquired pneumonia or ventilator-associated pneumonia are randomised in a 1:1 ratio to the intervention or control arm.

The main analysis population comprises patients with infections caused by Pseudomonas aeruginosa or carbapenem-resistant Enterobacterales. A secondary analysis population includes patients with infections caused by other specified multidrug-resistant Gram-negative organisms.

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.

The primary outcome is a composite of all-cause mortality or absence of improvement in Sequential Organ Failure Assessment (SOFA) score at Day 14 following the index culture.

Eligibility

Primary outcome measure(s)

• Composite of All-Cause Mortality or Absence of SOFA Score Improvement at Day 14 — Day 14 following index culture.
  Proportion of participants experiencing all-cause mortality within 14 days of the index blood or respiratory culture, or absence of improvement in Sequential Organ Failure Assessment (SOFA) score at Day 14. SOFA improvement is defined according to the prespecified baseline SOFA criteria in the study protocol.

Trial sites (21)