EaRly impAct theraPy With Ceftazidime-avibactam Via rapID Diagnostics

NCT ID: NCT05979545

Last Updated: 2024-03-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

1900 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-12-12

Study Completion Date

2026-12-31

Brief Summary

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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

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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.

Conditions

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Blood Stream Infections Ventilator Associated Pneumonia Healthcare Associated Infection Carbapenem-Resistant Enterobacteriaceae Infection Hospital-acquired Pneumonia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Rapid Diagnostics

Intervention Type 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.

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.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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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.

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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BioFire FilmArray BCID2 BioFire FilmArray Pneumonia Plus Panel BioFire FilmArray Pneumonia Panel

Eligibility Criteria

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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.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pfizer

INDUSTRY

Sponsor Role collaborator

Biomerieux inc

INDUSTRY

Sponsor Role collaborator

National University of Singapore

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David Paterson, Professor

Role: PRINCIPAL_INVESTIGATOR

National University of Singapore

Locations

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University Malaya Medical Centre

Kuala Lumpur, , Malaysia

Site Status NOT_YET_RECRUITING

Taichung Veterans General Hospital

Taichung, Xitun District, Taiwan

Site Status RECRUITING

Kaohsiung Medical University Hospital

Kaohsiung City, , Taiwan

Site Status NOT_YET_RECRUITING

Sunpasitthiprasong Hospital

Ubon Ratchathani, , Thailand

Site Status NOT_YET_RECRUITING

Countries

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Malaysia Taiwan Thailand

Central Contacts

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Kithalakshmi Vignesvaran

Role: CONTACT

Facility Contacts

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Norhabibah

Role: primary

Ying-Lan Li

Role: primary

Hannah Yan-Zhen Hsu

Role: primary

Sornsuda Setaphan, Ms

Role: primary

Other Identifiers

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23-0135

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

225457/Z/22/Z

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

20535

Identifier Type: OTHER

Identifier Source: secondary_id

ADVANCE-ID 22-002

Identifier Type: -

Identifier Source: org_study_id

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