Integrated Clinical Decision Support for Empiric Antibiotic Selection in Sepsis

NCT06103500 | Recruiting DMC

• 1 other identifier: 20230322-01T
• Study Type: interventional
• Target: 1,440
• Locations: 1 country
• Sites: 3

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.

Conditions

Sepsis; Bacterial Infections; Community-Acquired Infections; Hospital Infection

Outcome Measures

Primary Outcomes (1)

• Number of Patients De-escalated

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

  48 hours

Secondary Outcomes (19)

• Time to adequate therapy for positive blood cultures

  0-7 days

• Time to adequate therapy for positive non-screening cultures

  0-7 days

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

  48 hours

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

  48 hours

• Mortality

  90 days

Study Arms (2)

Clinical Decision Support Algorithm for Empiric Antibiotics in Sepsis

EXPERIMENTAL

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.

Other: Clinical Decision Support Algorithm for Empiric Antibiotics in Sepsis

Standard of Care

NO INTERVENTION

Non-intervention group. No decision support is provided. Patient care is routine.

Interventions

Clinical Decision Support Algorithm for Empiric Antibiotics in Sepsis OTHER

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

Also known as: Decision Support Tool

Clinical Decision Support Algorithm for Empiric Antibiotics in Sepsis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• Pregnancy/breastfeeding
• Documented end-of-life (palliative) care and are/will not be receiving ongoing antibiotic treatment.
• Already enrolled in the trial.
• 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.

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (3)

Trillium Health Partners

Mississauga, Ontario, Canada

RECRUITING

The Ottawa Hospital

Ottawa, Ontario, Canada

RECRUITING

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

RECRUITING

MeSH Terms

Conditions

Sepsis; Bacterial Infections; Community-Acquired Infections; Cross Infection

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bacterial Infections and Mycoses; Iatrogenic Disease; Disease Attributes

Study Officials

• Derek R Principal Investigator

  The Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Statistical analyst will be blind to treatment allocation.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Cluster Randomized Cross-Over Trial

Study Record Dates

• First Submitted: October 18, 2023
• First Posted: October 26, 2023
• Study Start: May 21, 2024
• Primary Completion: October 1, 2025
• Study Completion: October 1, 2025
• Last Updated: March 17, 2025

Record last verified: 2025-03

Locations

CA (3)