EaRly impAct theraPy With Ceftazidime-avibactam Via rapID Diagnostics

NCT05979545 | Recruiting Phase 4 DMC

• 4 other identifiers: ADVANCE-ID 22-00223-0135225457/Z/22/Z20535
• Study Type: interventional
• Target: 1,900
• Locations: 3 countries
• Sites: 4

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.

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

Outcome Measures

Primary Outcomes (1)

• 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

  14 days post index culture

Secondary Outcomes (5)

• Clinical response

  Day 7 and Day 14 post index culture

• All-cause mortality

  Day 14, Day 28, and Day 60 post index culture

• Functional outcome

  Day 14, Day 28 and Day 60 from collection of index culture

• Composite outcome

  Day 28 from index microbiology culture sample

• Implementation cost-Health Economics

  60 days since enrolment

Other Outcomes (1)

• Genomics studies

  Day 0

Study Arms (2)

Intervention

ACTIVE COMPARATOR

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

Control

NO INTERVENTION

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.

Interventions

Rapid Diagnostics DIAGNOSTIC_TEST

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.

Also known as: BioFire FilmArray BCID2, BioFire FilmArray Pneumonia Plus Panel, BioFire FilmArray Pneumonia Panel

Intervention

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• National University of Singapore: lead
• Pfizer: collaborator
• Biomerieux inc: collaborator

Study Sites (4)

University Malaya Medical Centre

Kuala Lumpur, 50603, Malaysia

NOT YET RECRUITING

Taichung Veterans General Hospital

Taichung, Xitun District, 1650, Taiwan

RECRUITING

Kaohsiung Medical University Hospital

Kaohsiung City, Taiwan

NOT YET RECRUITING

Sunpasitthiprasong Hospital

Ubon Ratchathani, 34000, Thailand

NOT YET RECRUITING

MeSH Terms

Conditions

Pneumonia, Ventilator-Associated; Cross Infection; Healthcare-Associated Pneumonia

Interventions

Rapid Diagnostic Tests

Condition Hierarchy (Ancestors)

Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Point-of-Care Testing; Point-of-Care Systems; Patient Care Management; Health Services Administration

Study Officials

• David Paterson, Professor

  National University of Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kithalakshmi Vignesvaran

CONTACT

90300178; kitha@nus.edu.sg

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 31, 2023
• First Posted: August 7, 2023
• Study Start: December 12, 2023
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 6, 2024

Record last verified: 2024-03

Locations

TH (1); MY (1); TW (2)