Clinical trial NCT05979545: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: 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
Lead sponsor: National University of Singapore
Sponsor class: OTHER
Collaborators: name: Pfizer
name: Biomerieux inc
First posted: 2023-08-07
Enrollment: 1900
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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

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.

Eligibility 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.

Primary outcomes:
measure: Composite endpoint of all-cause mortality and/or no improvement in SOFA score at Day 14 post index culture
timeFrame: 14 days post index culture
Secondary outcomes:
measure: Clinical response
timeFrame: Day 7 and Day 14 post index culture
measure: All-cause mortality
timeFrame: Day 14, Day 28, and Day 60 post index culture
measure: Functional outcome
timeFrame: Day 14, Day 28 and Day 60 from collection of index culture
measure: Composite outcome
timeFrame: Day 28 from index microbiology culture sample
measure: Implementation cost-Health Economics
timeFrame: 60 days since enrolment
Other outcomes:
measure: Genomics studies
timeFrame: Day 0
Locations:
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
state: Xitun District
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Hospital
city: Ubon Ratchathani
country: Thailand
facility: Sunpasitthiprasong Hospital
Study officials:
affiliation: National University of Singapore
name: David Paterson, Professor
role: PRINCIPAL_INVESTIGATOR
References: