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NCT Number: NCT06103500

Integrated Clinical Decision Support for Empiric Antibiotic Selection in Sepsis

As antibiotic resistance increases globally, it becomes more difficult to select empiric antibiotic therapy, particularly in patients with sepsis who stand to benefit from early adequate treatment. In particular it is difficult for clinicians to balance antibiotic stewardship principles (the need to avoid unnecessary prescribing of antibiotics that have an excessively broad spectrum of activity that favour resistance development) and under treatment. The integration of multiple risk variables for resistance are hard for clinicians to translate into clinical action, and is seemingly at odds with the natural inclination to provide heuristic/emotion-based antibiotic selection. The inappropriate treatment of sepsis is not uniformly too broad, or too narrow, and there is a need to optimize and tailor selection of antibiotic therapy to each patient, such that those that are at risk for resistant organisms receive broad therapy, and those that are not at risk, receive narrower antibiotic agents.

Clinicians need support picking the right antibiotic for each patient, and from this they can potentially drive reduction of unnecessarily broad antibiotic prescribing while preserving adequacy of treatment. Individualized clinical prediction models and decision support interventions are promising approaches that meet these needs by improving the classification of patient risk for antibiotic resistant or susceptible infections in sepsis. Unfortunately, few have been validated in the clinical setting and larger rigorous studies are needed to provide the evidence to support broader clinical adoption.

The investigators will perform a cluster randomized cross-over trial of an individualized antibiotic prescribing decision support intervention for providers treating hospitalized patients with suspected sepsis. The aim of this trial is to determine whether a stewardship led clinical decision support intervention can improve antibiotic de-escalation in patients with sepsis while maintaining or improving adequacy of antibiotic coverage. This decision support intervention will be based on a combination of proven decision heuristics (for Gram-positive organisms) and modelled predicted susceptibilities (for Gram-negative organisms) that are individualized to the patient. The primary outcome will be the proportion of patients de-escalated from their initial empiric regimen at 48 hours.

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Key information

Conditions

Sepsis Bacterial Infections Bacterial Infections and Mycoses Community-Acquired Infections Cross Infection Disease Attributes Hospital Infection Iatrogenic Disease Infections Inflammation Pathologic Processes Pathological Conditions, Signs and Symptoms Systemic Inflammatory Response Syndrome

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Trillium Health Partners, Mississauga, Ontario, Canada

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Admitted
  • Age >18 years old
  • Newly started (within 24 hours of assessment for eligibility) on at least one of the following antibiotic(s):

I. Vancomycin IV II. Linezolid III. Daptomycin IV. Clindamycin V. Cefazolin VI. Cloxacillin VII. Ceftriaxone VIII. Ceftazidime IX. Piperacillin-Tazobactam X. Meropenem (or Imipenem or Ertapenem) XI. Ciprofloxacin

  • Blood cultures ordered (within 12 hours before or after initiation of index antibiotics).

Overall Exclusion:

  • Pregnancy/breastfeeding
  • Documented end-of-life (palliative) care and are/will not be receiving ongoing antibiotic treatment.
  • Already enrolled in the trial.
  • Positive clinical culture results (those with speciation) for the index infection (within 72 hours) already available prior to assessment. Blood cultures with any Gram-positives will be an exclusion. Other cultures that are positive with a Gram-stain result but not speciation will not be an exclusion criteria.
  • Explanatory molecular test (e.g. legionella urinary antigen test, sars-cov-2 testing) within 72 hours prior to assessment.
  • Receipt of antimicrobials (not chronic suppression or prophylaxis) in the prior 24-72 hours (except if started in the outpatient setting or ED prior to admission in the 24-72 hours).
  • The index prescription is a continuation of an antibiotic given for suppressive chronic therapy or long-standing treatment of an established infection.
  • Index antibiotics are peri-operative only or ordered for <24 hours.
  • Cystic fibrosis.
  • Known to be enrolled in a trial that dictates antimicrobial selection.
  • Not eligible for any of the algorithms.

Treatment and study plan

Clinical Decision Support Algorithm for Empiric Antibiotics in Sepsis

Other

A clinical decision support algorithm for empiric antibiotic selection in suspected infection.

Other names: Decision Support Tool

Primary outcomes

  1. Number of Patients De-escalated

    Time frame: 48 hours

    De-escalation from empiric antibiotic regimen at 48 hours (or at time of discharge if earlier) from receipt of index antibiotics [Binary].

Secondary outcomes

  1. Time to adequate therapy for positive blood cultures

    Time frame: 0-7 days

    Time to adequate therapy for patients with positive blood cultures (hours from time of first index blood culture collection to first dose of agent(s) active against all pathogen(s) in the peri-index positive blood cultures). [Continuous] [Stratified by ampC organisms]

  2. Time to adequate therapy for positive non-screening cultures

    Time frame: 0-7 days

    Time to adequate therapy for patients with positive non-screening cultures including blood cultures (hours from time of first index blood culture collection to first dose of agent(s) active against all pathogen(s) in the peri-index positive cultures). [Continuous][Stratified by ampC organisms]

  3. Number of Patients Receiving Adequate Therapy at 48 hours based on blood cultures

    Time frame: 48 hours

    Receipt of adequate antibiotic therapy within 48 hours (or discharge if earlier) from first index blood culture collection for patients with positive blood cultures (active against all pathogens in peri-index positive blood cultures). [Binary]

  4. Number of Patients Receiving Adequate Therapy at 48 hours based on non-screening cultures

    Time frame: 48 hours

    Receipt of adequate antibiotic therapy within 48 hours (or discharge if earlier) from first index blood culture collection for patients with positive non-screening cultures including blood (active against all pathogens in peri-index positive cultures). [Binary]

  5. Mortality

    Time frame: 90 days

    In-hospital mortality, during index admission, and within 90 days of index event. [Binary]

  6. Length of stay

    Time frame: 0-90 days

    Hospital length of stay on index admission (days) up to 90 days. [Continuous]

  7. De-escalation extent

    Time frame: 48 hours

    Extent of antibiotic de-escalation at 48 hours from index or discharge if earlier (ordinal value up or down the de-escalation cascade, + escalation, - for de-escalation). [Integer from -infinity to infinity]

  8. Antibiotic spectrum at completion

    Time frame: Completion of therapy, up to 90 days

    Antibiotic spectrum rank at 7 days from index antibiotics (or discharge if earlier). [Ordinal]

  9. Number of Patients with C.difficile Infection

    Time frame: 90 days

    Positive stool testing for Clostridioides difficile during index admission, and within 90 days of index. [Binary]

  10. Number of Patients Requiring Dialysis

    Time frame: 90 days

    New requirement for dialysis during index admission, and within 90 days of index. [Binary]

  11. Days of antibiotic therapy

    Time frame: End of index admission, up to 90 days

    Total antibiotic days of therapy (DOT) during the first 7 days from index antibiotics (or prior to discharge if earlier), including by spectrum-level. [Continuous]

  12. Number of Patients with Antibiotic Escalation

    Time frame: 48 hours

    Newly started Gram-positive or Gram-negative coverage, or increases in spectrum of antibiotic therapy, as part of the intervention recommendation. [Binary]

  13. Time to De-escalation

    Time frame: 0-7 days

    Description: Time to antibiotic de-escalation (hours from receipt of index antibiotics). [Continuous][Stratified by ampC organisms]

  14. Number of Patients with Recommended change in Gram-negative coverage

    Time frame: At time of assessment (0 days)

    Recommended change in antibiotic therapy by Gram-negative model. [Binary]

  15. Number of Patients with Accepted change in Gram-negative coverage

    Time frame: Within 24 hours

    Recommended change in antibiotic therapy by Gram-negative model was accepted (acceptance defined as change to some or all of the therapy as recommended within 24 hours of index). [Binary]

  16. Number of Patients with Recommended change in Gram-positive coverage

    Time frame: At time of assessment (0 days)

    Recommended change in antibiotic therapy by Gram-positive algorithm. [Binary]

  17. Number of Patients with Accepted change in Gram-positive coverage

    Time frame: Within 24 hours

    Recommended change in antibiotic therapy by Gram-positive algorithm was accepted and ordered (acceptance defined as change to some or all of the therapy as recommended within 24 hours of index). [Binary]

  18. Number of Patients with Non-recommended escalation at 7 days

    Time frame: 7 days

    Escalation of antibiotic therapy (apart from recommended escalation) within 7 days of receipt of index antibiotics (or prior to discharge if earlier). [Binary]

  19. Number of Patients with ICU admit or mortality

    Time frame: 7 days

    Admitted to ICU on day 7 or not alive at day 7 from receipt of index antibiotics. [Binary]

Sponsors and collaborators

Lead sponsor

Ottawa Hospital Research Institute

Other

Collaborators

  • Canadian Institutes of Health Research (CIHR)

Registry information

Official study title

Integrated Clinical Decision Support for Empiric Antibiotic Selection in Sepsis: A Cluster Randomized Cross-Over Trial (IDEAS-CRXO)

Acronym: IDEAS-CRXO

Important dates

Study start
2024
Primary completion
2025
Study completion
2025
First posted
Oct 26, 2023
Registry last updated
Mar 17, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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