Back to resultsUsing Biomarkers to Optimize Antibiotic Strategies in Sepsis
Primary Purpose
Sepsis
Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Biomarker Algorithm Intervention
Sponsored by
About this trial
This is an interventional diagnostic trial for Sepsis focused on measuring Sepsis, Systemic Inflammatory Response Syndrome (SIRS), Antibiotic use, Intensive Care Unit
Eligibility Criteria
Inclusion Criteria:
SIRS Criteria
SIRS is considered to be present when patients have more than one of the following clinical findings:
- body temperature >38°C or <36°C
- heart rate >90 min-1
- respiratory rate of >20 min-1 or a Paco2 of <32 mm Hg
- and a white blood cell count of >12,000 cells µL-1 or <4,000 µL-1
- new empiric antibiotic therapy is initiated, indicating the suspicion of infection. Accepted criteria for SIRS will be used for the Medical Intensive Care Unit and Surgical Intensive Care Unit populations, with appropriate age-specific vital signs definitions to help make the definitions relevant for the Pediatric Intensive Care Unit population.
Exclusion Criteria:
- a code status of "do not resuscitate"
- absence of initiation or expansion of antibiotic therapy despite meeting criteria for sepsis
- presence of an immunocompromising condition.
An immunocompromising condition will be defined as one of the following:
- human immunodeficiency virus (HIV) infection with a t-helper cell (CD4) count <200 cell/mm3; 2) immunosuppressive therapy after organ transplantation
- neutropenia (<500 neutrophils/mm3)
- active chemotherapy within the 3 months preceding eligibility or
- diagnosis of cystic fibrosis.
These criteria all represent conditions in which antibiotic use is much less likely to be decreased regardless of the results of a biomarker and are consistent with exclusion criteria used in past studies of the impact of biomarkers.
Sites / Locations
- Hospital of the University of Pennsylvania - Medical Intensive Care Unit
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Experimental
Arm Label
Observational
Biomarker Algorithm Intervention
Arm Description
9 blood biomarkers (including C reactive protein and Procalcitonin) will be assessed across 3 days. Results will not be shared with the subject's medical team. At 3 days, the definitive diagnosis of infection will be determined using Center for Disease Control (CDC) criteria; this will serve as the gold standard for determining biomarker test characteristics. Additional data to collect: demographics, comorbidities, medication use (like antibiotics), lab cultures, x-rays, sepsis resolution, length of hospital stay, and ultimate outcome (i.e., discharge, death). Phase I will identify the biomarker(s) providing the greatest negative predictive value in identifying patients at very low likelihood bacterial infection.
The Algorithm arm is equivalent to the intervention. Biomarker algorithm along with the patient's biomarker assay results will be given to clinical team to assist in deciding to continue antibiotics. The intervention will consist of using the biomarker identified as useful in Phase I to compile an algorithm along containing the patient's biomarker assay results and providing this as additional information for a clinical team consider using to assist in deciding to continue antibiotics. Biomarker algorithms may be different for adult versus pediatric patients, and across different types of ICUs.
Outcomes
Primary Outcome Measures
Duration of antibiotic therapy started upon enrollment for presumed sepsis
The primary outcome is the duration of antibiotic treatment after enrollment, expressed in days. This variable will focus specifically on the antibiotic agents given for the episode of presumed sepsis for which the patient was included in the study.
Secondary Outcome Measures
Subject's Final Disposition
This includes assessing ICU mortality, hospital mortality, or hospital discharge as an ultimate outcome.
Full Information
NCT ID
NCT02207114
First Posted
February 3, 2014
Last Updated
March 6, 2023
Sponsor
University of Pennsylvania
1. Study Identification
Unique Protocol Identification Number
NCT02207114
Brief Title
Using Biomarkers to Optimize Antibiotic Strategies in Sepsis
Official Title
Southeastern Pennsylvania Adult and Pediatric Prevention Epicenter Network - Randomized Control Trial
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 2012 (undefined)
Primary Completion Date
December 2016 (Actual)
Study Completion Date
December 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Pennsylvania
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The proposed work will provide critical insights into the potential impact of a biomarker-based algorithm on reducing unnecessary antibiotic use in different adult and pediatric/neonatal ICU's. This proposal will also assess the costs (or savings) of a biomarker-based intervention. Overall, the results of this work will be critical in informing future strategies to eliminate unnecessary antibiotic use and curb the continued rise in antimicrobial resistance.
Detailed Description
The goal of this project is reduce unnecessary use of antibiotics in the ICU. The purpose of Phase I of the study is to identify the biomarker, or combination of biomarkers, that provides optimal test characteristics in identifying adults and children/neonates with presumed sepsis who have a very low likelihood of bacterial infection. Results of Phase I will result in development of a biomarker-based algorithm to inform need for antibiotic use in ICU patients. In Phase II, the impact of this biomarker-based algorithm on reducing antibiotic use in the ICU will be determined. Costs or savings associated with the algorithm will also be assessed.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sepsis
Keywords
Sepsis, Systemic Inflammatory Response Syndrome (SIRS), Antibiotic use, Intensive Care Unit
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
145 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Observational
Arm Type
No Intervention
Arm Description
9 blood biomarkers (including C reactive protein and Procalcitonin) will be assessed across 3 days. Results will not be shared with the subject's medical team. At 3 days, the definitive diagnosis of infection will be determined using Center for Disease Control (CDC) criteria; this will serve as the gold standard for determining biomarker test characteristics. Additional data to collect: demographics, comorbidities, medication use (like antibiotics), lab cultures, x-rays, sepsis resolution, length of hospital stay, and ultimate outcome (i.e., discharge, death). Phase I will identify the biomarker(s) providing the greatest negative predictive value in identifying patients at very low likelihood bacterial infection.
Arm Title
Biomarker Algorithm Intervention
Arm Type
Experimental
Arm Description
The Algorithm arm is equivalent to the intervention. Biomarker algorithm along with the patient's biomarker assay results will be given to clinical team to assist in deciding to continue antibiotics.
The intervention will consist of using the biomarker identified as useful in Phase I to compile an algorithm along containing the patient's biomarker assay results and providing this as additional information for a clinical team consider using to assist in deciding to continue antibiotics. Biomarker algorithms may be different for adult versus pediatric patients, and across different types of ICUs.
Intervention Type
Other
Intervention Name(s)
Biomarker Algorithm Intervention
Intervention Description
The intervention will consist of using the biomarker identified as useful in Phase I to compile an algorithm along containing the patient's biomarker assay results and providing this as additional information for a clinical team consider using to assist in deciding to continue antibiotics. Biomarker algorithms may be different for adult versus pediatric patients, and across different types of ICUs.
Primary Outcome Measure Information:
Title
Duration of antibiotic therapy started upon enrollment for presumed sepsis
Description
The primary outcome is the duration of antibiotic treatment after enrollment, expressed in days. This variable will focus specifically on the antibiotic agents given for the episode of presumed sepsis for which the patient was included in the study.
Time Frame
Two years
Secondary Outcome Measure Information:
Title
Subject's Final Disposition
Description
This includes assessing ICU mortality, hospital mortality, or hospital discharge as an ultimate outcome.
Time Frame
Participants will be followed for the duration of hospital stay, an expected average of 6 days
Other Pre-specified Outcome Measures:
Title
Length of stay
Description
A secondary outcome of length of stay both in the Intensive Care Unit as well as total hospital stay after enrollment will be assessed.
Time Frame
Participants will be followed for the duration of hospital stay, an expected average of 6 days
Title
Clinical Cure
Description
This secondary outcome measure is defined as resolution of sepsis. Clinical signs and symptoms present at the time of enrollment as well as the presence in any clinical cultures of antimicrobial resistant organisms not present prior to enrollment will be ascertained.
Time Frame
Participants will be followed for the duration of hospital stay, an expected average of 6 days
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
SIRS Criteria
SIRS is considered to be present when patients have more than one of the following clinical findings:
body temperature >38°C or <36°C
heart rate >90 min-1
respiratory rate of >20 min-1 or a Paco2 of <32 mm Hg
and a white blood cell count of >12,000 cells µL-1 or <4,000 µL-1
new empiric antibiotic therapy is initiated, indicating the suspicion of infection. Accepted criteria for SIRS will be used for the Medical Intensive Care Unit and Surgical Intensive Care Unit populations, with appropriate age-specific vital signs definitions to help make the definitions relevant for the Pediatric Intensive Care Unit population.
Exclusion Criteria:
a code status of "do not resuscitate"
absence of initiation or expansion of antibiotic therapy despite meeting criteria for sepsis
presence of an immunocompromising condition.
An immunocompromising condition will be defined as one of the following:
human immunodeficiency virus (HIV) infection with a t-helper cell (CD4) count <200 cell/mm3; 2) immunosuppressive therapy after organ transplantation
neutropenia (<500 neutrophils/mm3)
active chemotherapy within the 3 months preceding eligibility or
diagnosis of cystic fibrosis.
These criteria all represent conditions in which antibiotic use is much less likely to be decreased regardless of the results of a biomarker and are consistent with exclusion criteria used in past studies of the impact of biomarkers.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ebbing Lautenbach, MD,MPH,MSCE
Organizational Affiliation
Univeristy of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital of the University of Pennsylvania - Medical Intensive Care Unit
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Using Biomarkers to Optimize Antibiotic Strategies in Sepsis
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