Using Biomarkers to Optimize Antibiotic Strategies in Sepsis

Study Description

Brief Summary

Detailed Description

Condition or disease	Intervention/treatment	Phase
Sepsis	Other: Biomarker Algorithm Intervention Other Names	N/A

Tracking Information

First Submitted Date	February 03, 2014
Last Update Posted Date	February 05, 2018
Start Date	January 01, 2012
Anticipated Completion Date	April 01, 2018
Primary Completion Date	December 01, 2016
Results First Submitted Date	N/A
Received Results Disposit Date	N/A

Current Primary Outcome Measures

• Duration of antibiotic therapy started upon enrollment for presumed sepsis [Time Frame: Two years]

  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.

Original Primary Outcome Measures

Current Secondary Outcome Measures

• Subject's Final Disposition [Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 6 days]

  This includes assessing ICU mortality, hospital mortality, or hospital discharge as an ultimate outcome.

Original Secondary Outcome Measures

Study Design

Brief Title	Using Biomarkers to Optimize Antibiotic Strategies in Sepsis
Official Title	Southeastern Pennsylvania Adult and Pediatric Prevention Epicenter Network - Randomized Control Trial
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.
Study Type	Interventional
Study Phase	N/A
Estimated Enrollment	145
Allocation	Randomized
Interventional Model	Parallel Assignment
Masking	None (Open Label)
Primary Purpose	Diagnostic
Conditions	Sepsis
Target Follow-Up Duration	N/A
Biospecimen:	N/A
Sampling Method	N/A
Study Population	N/A
Intervention	Other: Biomarker Algorithm Intervention 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. Other Names
Study Groups/Cohorts	Observational 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. Biomarker Algorithm Intervention 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.
Study Arms	Experimental Biomarker Algorithm Intervention 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. Other : Biomarker Algorithm Intervention 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.

Arm

Intervention/Treatment

Experimental Biomarker Algorithm Intervention 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.

Other : Biomarker Algorithm Intervention 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.

Recruitment Information

Recruitment Status:	Active, not recruiting
Enrollment	145
Completion Date	April 01, 2018
Eligibility Criteria:	Inclusion Criteria: 1. 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 2. 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: 1. a code status of "do not resuscitate" 2. absence of initiation or expansion of antibiotic therapy despite meeting criteria for sepsis 3. 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.
Gender	All
Age	N/A to N/A
Accepts Healthy Volunteers	No
Contacts	Not Available
Listed Location Countries	United States

Administrative Information

NCT Number:	NCT02207114
Other Study ID Numbers	813623
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Studies a U.S. FDA-regulated Drug Product: No Studies a U.S. FDA-regulated Device Product: No Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement	Not Available
Responsible Party	,
Study Sponsor	University of Pennsylvania
Collaborators	Not Available
Investigators	Principal Investigator Ebbing Lautenbach, MD,MPH,MSCE Univeristy of Pennsylvania