Integrated Clinical Decision Support for Empiric Antibiotic Selection in Sepsis

Sepsis Clinical Trial

— IDEAS-CRXO  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06103500
• Other study ID #: 20230322-01T
• Status: Not yet recruiting
• Phase: N/A
• Start date: July 1, 2024
• Est. completion date: March 31, 2025

Study information

• Verified date: April 2024
• Source: Ottawa Hospital Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 1400
• Est. completion date: March 31, 2025
• Est. primary completion date: January 2, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

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.

Related Conditions & MeSH terms

• Bacterial Infections
• Communicable Diseases
• Community-Acquired Infections
• Cross Infection
• Hospital Infection
• Infections
• Sepsis
• Toxemia

Intervention

Other:
• Clinical Decision Support Algorithm for Empiric Antibiotics in Sepsis
A clinical decision support algorithm for empiric antibiotic selection in suspected infection.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Ottawa Hospital Research Institute	Canadian Institutes of Health Research (CIHR)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Patients De-escalated	De-escalation from empiric antibiotic regimen within 48 hours of receipt of antibiotics [Binary].	48 hours
Secondary	Time to adequate therapy	Time to adequate therapy for patients with positive blood cultures (hours from time of blood culture collection to first dose of agent(s) active against all pathogen(s) in the positive culture).	0-7 days
Secondary	Number of Patients Receiving Adequate Therapy at 48 hours	Receipt of adequate antibiotic therapy within 48 hours from blood culture collection for patients with positive cultures.	48 hours
Secondary	Mortality	In-hospital mortality, during index admission, and within 90 days of index event.	90 days
Secondary	Length of stay	Hospital length of stay on index admission (days).	0-90 days
Secondary	De-escalation extent	Extent of antibiotic de-escalation (ordinal value up or down the de-escalation cascade)	48 hours
Secondary	Antibiotic spectrum at completion	Antibiotic spectrum ranking on the last day of antibiotic treatment.	Completion of therapy, up to 90 days
Secondary	C.difficile Infection	Positive stool testing for C. difficile during index admission, and within 90 days of index.	90 days
Secondary	Dialysis	New requirement for dialysis during index admission, and within 90 days of index.	90 days
Secondary	Days of antibiotic therapy	Total antibiotic days of therapy (DOT) during index admission, including by spectrum-level.	End of index admission, up to 90 days
Secondary	Escalation	Newly started Gram-positive or Gram-negative coverage, or increases in spectrum of antibiotic therapy, as part of the intervention recommendation.	48hrs
Secondary	Recommended change in Gram-negative coverage	Recommended change in antibiotic therapy by Gram-negative model.	At time of assessment
Secondary	Accepted change in Gram-negative coverage	Recommended change in antibiotic therapy by Gram-negative model was accepted and ordered.	At time of assessment
Secondary	Recommended change in Gram-positive coverage	Recommended change in antibiotic therapy by Gram-positive algorithm.	at time of assessment
Secondary	Accepted change in Gram-positive coverage	Recommended change in antibiotic therapy by Gram-positive algorithm was accepted and ordered.	At 48 hrs
Secondary	Non-recommended escalation at 7 days	Escalation of antibiotic therapy (apart from recommended escalation) within 7 days of receipt of initial antibiotics	7 days
Secondary	ICU admit or mortality	ICU admission or death at 7 days from receipt of initial antibiotics	7 days