Clinical trial NCT06103500: Integrated Clinical Decision Support for Empiric Antibiotic Selection in Sepsis
Official title: Integrated Clinical Decision Support for Empiric Antibiotic Selection in Sepsis: A Cluster Randomized Cross-Over Trial (IDEAS-CRXO)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Sepsis
Bacterial Infections
Community-Acquired Infections
Hospital Infection
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2023-10-26
Enrollment: 1440
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Cluster Randomized Cross-Over Trial
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Admitted
2. Age \>18 years old
3. 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
4. Blood cultures ordered (within 12 hours before or after initiation of index antibiotics).

Overall Exclusion:

1. Pregnancy/breastfeeding
2. Documented end-of-life (palliative) care and are/will not be receiving ongoing antibiotic treatment.
3. Already enrolled in the trial.
4. 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.
5. Explanatory molecular test (e.g. legionella urinary antigen test, sars-cov-2 testing) within 72 hours prior to assessment.
6. 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).
7. The index prescription is a continuation of an antibiotic given for suppressive chronic therapy or long-standing treatment of an established infection.
8. Index antibiotics are peri-operative only or ordered for \<24 hours.
9. Cystic fibrosis.
10. Known to be enrolled in a trial that dictates antimicrobial selection.
11. Not eligible for any of the algorithms.

Primary outcomes:
measure: Number of Patients De-escalated
timeFrame: 48 hours
Secondary outcomes:
measure: Time to adequate therapy for positive blood cultures
timeFrame: 0-7 days
measure: Time to adequate therapy for positive non-screening cultures
timeFrame: 0-7 days
measure: Number of Patients Receiving Adequate Therapy at 48 hours based on blood cultures
timeFrame: 48 hours
measure: Number of Patients Receiving Adequate Therapy at 48 hours based on non-screening cultures
timeFrame: 48 hours
measure: Mortality
timeFrame: 90 days
measure: Length of stay
timeFrame: 0-90 days
measure: De-escalation extent
timeFrame: 48 hours
measure: Antibiotic spectrum at completion
timeFrame: Completion of therapy, up to 90 days
measure: Number of Patients with C.difficile Infection
timeFrame: 90 days
measure: Number of Patients Requiring Dialysis
timeFrame: 90 days
measure: Days of antibiotic therapy
timeFrame: End of index admission, up to 90 days
measure: Number of Patients with Antibiotic Escalation
timeFrame: 48 hours
measure: Time to De-escalation
timeFrame: 0-7 days
measure: Number of Patients with Recommended change in Gram-negative coverage
timeFrame: At time of assessment (0 days)
measure: Number of Patients with Accepted change in Gram-negative coverage
timeFrame: Within 24 hours
measure: Number of Patients with Recommended change in Gram-positive coverage
timeFrame: At time of assessment (0 days)
measure: Number of Patients with Accepted change in Gram-positive coverage
timeFrame: Within 24 hours
measure: Number of Patients with Non-recommended escalation at 7 days
timeFrame: 7 days
measure: Number of Patients with ICU admit or mortality
timeFrame: 7 days
Other outcomes:
Locations:
city: Mississauga
country: Canada
facility: Trillium Health Partners
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
affiliation: The Ottawa Hospital Research Institute
name: Derek R Principal Investigator
role: PRINCIPAL_INVESTIGATOR
References: