Impact of Rapid Pathogen Identification From Blood Cultures (RABbIT)

NCT ID: NCT02743585

Last Updated: 2019-09-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 832 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-20
• Study Completion Date: 2020-07-02

Brief Summary

Septic shock carries high mortality, which may be exacerbated by inappropriate initial therapy. Inappropriate therapy may result from unanticipated antimicrobial resistance. Conversely, positive blood cultures may result from contamination, leading to unnecessary therapy and procedures and possibly prolonged hospitalization. Clinicians may also resort to broad spectrum antimicrobials and be hesitant to de-escalate while awaiting susceptibility results.

The investigators hypothesize that rapid identification of pathogens and antimicrobial resistance will ameliorate the above problems and improve time to optimal therapy, avoid unnecessary therapy and ultimately improve patient outcomes. While there are a number of in-vitro and uncontrolled clinical studies, there is a paucity of well-designed clinical trials objectively examining the real-world clinical and health-economic impact of such technology. To date only one randomised trial has been performed in the US (ClinicalTrials.gov NCT01898208), at a setting with low endemic rates of antimicrobial resistance. This is a companion study to NCT01898208. The investigators aim to study the clinical impact and cost-effectiveness of a strategy for rapid pathogen and resistance detection in a setting with a moderate to high levels of antimicrobial resistance.

Detailed Description

Hypothesis:

1. Rapid pathogen identification from blood cultures, including early identification of resistance (via specific genetic markers or phenotypic tests), will allow timelier initiation of appropriate antibiotic therapy and improved patient outcomes

2. Rapid organism identification from blood cultures will allow timelier initiation of effective and optimal antibiotic therapy; minimizing the use of unnecessary antibiotics, including combination therapy

Devices to be studied for this proposed study:

1. BCID panel (Biofire Diagnostics Inc., bioMerieux) : The BCID panel is an FDA-approved nucleic acid amplification test (based on nested polymerase chain reaction) which detects Gram positive, Gram negative, the major Candida species and antimicrobial resistance markers (mecA for methicillin resistance, van A/B for vancomycin resistance, blaKPC for Klebsiella pneumoniae carbapenemase (KPC)) directly from positive blood cultures in < 1 - 1.5 hours

2. Rosco Diagnostica extended-spectrum beta-lactamase (ESBL) and carbapenemase screen kit (Rosco Diagnostica): These kits are CE-marked (Approved in the European Union) rapid chromogenic tests for ESBL/ carbapenemase detection from both blood cultures and cultured bacterial colonies.

Conditions

Bacteremia; Sepsis; Fungemia; Blood Stream Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: SINGLE

Study Groups

Rapid diagnostic arm

Standard Tan Tock Seng Hospital (TTSH) practices (bacterial culture and susceptibility testing) AND FilmArray Blood Culture ID (BCID) Panel test AND Rosco Diagnostica ESBL and carbapenemase screen will be performed.

The Interventions to be administered are the rapid diagnostic tests: FilmArray Blood Culture ID (BCID) Panel test AND Rosco Diagnostica ESBL and carbapenemase screen.

Subjects will be recruited 8am-3pm daily, weekdays only. Results of the BCID and Rosco test will be communicated to the managing physicians by phone in real-time.

Group Type: EXPERIMENTAL

Filmarray Blood Culture ID (BCID) panel

Intervention Type: DEVICE

The BCID panel is an FDA-approved nucleic acid amplification test (based on nested polymerase chain reaction) which detects Gram positive, Gram negative, the major Candida species and antimicrobial resistance markers (mecA for methicillin resistance, van A/B for vancomycin resistance, blaKPC for KPC carbapenemase) directly from positive blood cultures in \< 1 - 1.5 hours

Rosco Diagnostica ESBL/carbapenemase screen kit

Intervention Type: DEVICE

These kits are CE-marked (Approved in the European Union) rapid chromogenic tests for extended-spectrum beta-lactamase / carbapenemase detection from both blood cultures and cultured bacterial colonies.

Standard of care (control)

Standard Tan Tock Seng Hospital (TTSH) practices (bacterial culture and susceptibility testing) will be used. FilmArray BCID and Rosco Diagnostica ESBL and carbapenemase screen will NOT be performed. Subjects will be recruited 8am-3pm daily, weekdays only.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Filmarray Blood Culture ID (BCID) panel

The BCID panel is an FDA-approved nucleic acid amplification test (based on nested polymerase chain reaction) which detects Gram positive, Gram negative, the major Candida species and antimicrobial resistance markers (mecA for methicillin resistance, van A/B for vancomycin resistance, blaKPC for KPC carbapenemase) directly from positive blood cultures in \< 1 - 1.5 hours

Intervention Type: DEVICE

Rosco Diagnostica ESBL/carbapenemase screen kit

These kits are CE-marked (Approved in the European Union) rapid chromogenic tests for extended-spectrum beta-lactamase / carbapenemase detection from both blood cultures and cultured bacterial colonies.

Intervention Type: DEVICE

Other Intervention Names

BCID

Eligibility Criteria

Inclusion Criteria

1. Age > 21 years and above to 103 years

2. Blood culture flagged positive on automated instrument, with Gram positive, Gram negative bacteria or Yeast on Gram staining (including polymicrobial blood cultures)

3. Ability to provide informed consent or ability to obtain informed consent from legal guardian/representative (verbal and written)

Exclusion Criteria

1. Patients whose blood cultures turn positive, but have no organism seen on Gram stain.

2. Patients who have been previously enrolled.

3. Patients who withdraw their consent (verbal or written).

4. Patients with any positive blood culture in the preceding 7 days.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 103 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mayo Clinic

OTHER

Sponsor Role: collaborator

Tan Tock Seng Hospital

OTHER

Sponsor Role: lead

Responsible Party

Shawn Vasoo

Consultant

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Shawn Vasoo, MD

Role: PRINCIPAL_INVESTIGATOR

Tan Tock Seng Hospital

Partha P De, MD

Role: PRINCIPAL_INVESTIGATOR

Tan Tock Seng Hospital

Christine B Teng, MSc

Role: PRINCIPAL_INVESTIGATOR

National University of Singapore/Tan Tock Seng Hospital

Locations

Tan Tock Seng Hospital

Singapore, , Singapore

Countries

Singapore

References

Ong SWX, Hon PY, Wee SSH, Chia JWZ, Mendis S, Izharuddin E, Lin RJ, Chia PY, Sim RCS, Chen MI, Chow A, Yoong J, Lye DC, Teng CB, Tambyah PA, Banerjee R, Patel R, De PP, Vasoo S. Accuracy of a Rapid Multiplex Polymerase Chain Reaction Plus a Chromogenic Phenotypic Test Algorithm for Detection of Extended-Spectrum beta-Lactamase and Carbapenemase-Producing Gram-Negative Bacilli in Positive Blood Culture Bottles. Clin Infect Dis. 2022 May 30;74(10):1850-1854. doi: 10.1093/cid/ciab848.

Reference Type: DERIVED

PMID: 34554228 (View on PubMed)

Other Identifiers

2015/00255

Identifier Type: -

Identifier Source: org_study_id