Integrated Clinical Decision Support for Empiric Antibiotic Selection in Sepsis

Not Applicable

Not yet recruiting

• Conditions: Sepsis; Bacterial Infections; Hospital Infection; Community-Acquired Infections
• Interventions: Other: Clinical Decision Support Algorithm for Empiric Antibiotics in Sepsis

• Registration Number: NCT06103500
• Lead Sponsor: Ottawa Hospital Research Institute

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 within 48 hours.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-10-18
• Study First Submitted QC: 2023-10-25
• Study First Posted: 2023-10-26
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-02
• Last Update Posted: 2024-04-03
• Study Start: 2024-07-01
• Primary Completion: 2025-01-02
• Study Completion: 2025-03-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 1400

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 II. Linezolid III. Daptomycin IV. Cefazolin V. Cloxacillin VI. Ceftriaxone VII. Ceftazidime VIII. Piperacillin-Tazobactam IX. Meropenem (or Imipenem or Ertapenem) X. Ciprofloxacin (or Moxifloxacin or Levofloxacin) XI. Gentamicin (or Tobramycin).

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

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Exclusion Criteria

1. Documented end-of-life (palliative) care.
2. Already enrolled in the trial.
3. Positive clinical culture results for the index infection already available prior to giving advice.
4. Receipt of antimicrobials (not chronic suppression) in the prior 24-72 hours.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Clinical Decision Support Algorithm for Empiric Antibiotics in Sepsis	Clinical Decision Support Algorithm for Empiric Antibiotics in Sepsis	The planned intervention consists of a pharmacist-facilitated clinical decision support intervention, where pharmacists provide options and recommendations on empiric sepsis antibiotic selection to hospital providers.

Primary Outcome Measures

Name	Time	Method
Number of Patients De-escalated	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 Outcome Measures

Name	Time	Method
Time to adequate therapy for positive blood cultures	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). \[Continuous\]
Time to adequate therapy for positive non-screening cultures	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). \[Continuous\]
Number of Patients Receiving Adequate Therapy at 48 hours based on blood cultures	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). \[Binary\]
Number of Patients Receiving Adequate Therapy at 48 hours based on non-screening cultures	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). \[Binary\]
Mortality	90 days	In-hospital mortality, during index admission, and within 90 days of index event. \[Binary\]
Length of stay	0-90 days	Hospital length of stay on index admission (days) up to 90 days. \[Continuous\]
De-escalation extent	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). \[Integer from -infinity to infinity\]
Antibiotic spectrum at completion	Completion of therapy, up to 90 days	Antibiotic spectrum rank at 7 days from index antibiotics (or discharge if earlier). \[Ordinal\]
Number of Patients with C.difficile Infection	90 days	Positive stool testing for Clostridioides difficile during index admission, and within 90 days of index. \[Binary\]
Number of Patients Requiring Dialysis	90 days	New requirement for dialysis during index admission, and within 90 days of index. \[Binary\]
Days of antibiotic therapy	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. \[Continuous\]
Number of Patients with Antibiotic Escalation	48 hours	Newly started Gram-positive or Gram-negative coverage, or increases in spectrum of antibiotic therapy, as part of the intervention recommendation. \[Binary\]
Number of Patients with Recommended change in Gram-negative coverage	At time of assessment (0 days)	Recommended change in antibiotic therapy by Gram-negative model. \[Binary\]
Number of Patients with Accepted change in Gram-negative coverage	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). \[Binary\]
Number of Patients with Recommended change in Gram-positive coverage	At time of assessment (0 days)	Recommended change in antibiotic therapy by Gram-positive algorithm. \[Binary\]
Number of Patients with Accepted change in Gram-positive coverage	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). \[Binary\]
Number of Patients with Non-recommended escalation at 7 days	7 days	Escalation of antibiotic therapy (apart from recommended escalation) within 7 days of receipt of index antibiotics (or prior to discharge if earlier). \[Binary\]
Number of Patients with ICU admit or mortality	7 days	Admitted to ICU on day 7 or not alive at day 7 from receipt of index antibiotics. \[Binary\]

Trial Locations

Locations (3)

Trillium Health Partners; 🇨🇦 Mississauga, Ontario, Canada

The Ottawa Hospital; 🇨🇦 Ottawa, Ontario, Canada

Sunnybrook Health Sciences Centre; 🇨🇦 Toronto, Ontario, Canada