<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02207114</url>
  </required_header>
  <id_info>
    <org_study_id>813623</org_study_id>
    <nct_id>NCT02207114</nct_id>
  </id_info>
  <brief_title>Using Biomarkers to Optimize Antibiotic Strategies in Sepsis</brief_title>
  <official_title>Southeastern Pennsylvania Adult and Pediatric Prevention Epicenter Network - Randomized Control Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Pennsylvania</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The proposed work will provide critical insights into the potential impact of a&#xD;
      biomarker-based algorithm on reducing unnecessary antibiotic use in different adult and&#xD;
      pediatric/neonatal ICU's. This proposal will also assess the costs (or savings) of a&#xD;
      biomarker-based intervention. Overall, the results of this work will be critical in informing&#xD;
      future strategies to eliminate unnecessary antibiotic use and curb the continued rise in&#xD;
      antimicrobial resistance.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The goal of this project is reduce unnecessary use of antibiotics in the ICU. The purpose of&#xD;
      Phase I of the study is to identify the biomarker, or combination of biomarkers, that&#xD;
      provides optimal test characteristics in identifying adults and children/neonates with&#xD;
      presumed sepsis who have a very low likelihood of bacterial infection. Results of Phase I&#xD;
      will result in development of a biomarker-based algorithm to inform need for antibiotic use&#xD;
      in ICU patients. In Phase II, the impact of this biomarker-based algorithm on reducing&#xD;
      antibiotic use in the ICU will be determined. Costs or savings associated with the algorithm&#xD;
      will also be assessed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>January 2012</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Actual">December 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Duration of antibiotic therapy started upon enrollment for presumed sepsis</measure>
    <time_frame>Two years</time_frame>
    <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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Subject's Final Disposition</measure>
    <time_frame>Participants will be followed for the duration of hospital stay, an expected average of 6 days</time_frame>
    <description>This includes assessing ICU mortality, hospital mortality, or hospital discharge as an ultimate outcome.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Length of stay</measure>
    <time_frame>Participants will be followed for the duration of hospital stay, an expected average of 6 days</time_frame>
    <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.</description>
  </other_outcome>
  <other_outcome>
    <measure>Clinical Cure</measure>
    <time_frame>Participants will be followed for the duration of hospital stay, an expected average of 6 days</time_frame>
    <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.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">145</enrollment>
  <condition>Sepsis</condition>
  <arm_group>
    <arm_group_label>Observational</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Biomarker Algorithm Intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <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.&#xD;
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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Biomarker Algorithm Intervention</intervention_name>
    <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.</description>
    <arm_group_label>Biomarker Algorithm Intervention</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. SIRS Criteria&#xD;
&#xD;
             SIRS is considered to be present when patients have more than one of the following&#xD;
             clinical findings:&#xD;
&#xD;
               -  body temperature &gt;38°C or &lt;36°C&#xD;
&#xD;
               -  heart rate &gt;90 min-1&#xD;
&#xD;
               -  respiratory rate of &gt;20 min-1 or a Paco2 of &lt;32 mm Hg&#xD;
&#xD;
               -  and a white blood cell count of &gt;12,000 cells µL-1 or &lt;4,000 µL-1&#xD;
&#xD;
          2. new empiric antibiotic therapy is initiated, indicating the suspicion of infection.&#xD;
             Accepted criteria for SIRS will be used for the Medical Intensive Care Unit and&#xD;
             Surgical Intensive Care Unit populations, with appropriate age-specific vital signs&#xD;
             definitions to help make the definitions relevant for the Pediatric Intensive Care&#xD;
             Unit population.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. a code status of &quot;do not resuscitate&quot;&#xD;
&#xD;
          2. absence of initiation or expansion of antibiotic therapy despite meeting criteria for&#xD;
             sepsis&#xD;
&#xD;
          3. presence of an immunocompromising condition.&#xD;
&#xD;
        An immunocompromising condition will be defined as one of the following:&#xD;
&#xD;
          -  human immunodeficiency virus (HIV) infection with a t-helper cell (CD4) count &lt;200&#xD;
             cell/mm3; 2) immunosuppressive therapy after organ transplantation&#xD;
&#xD;
          -  neutropenia (&lt;500 neutrophils/mm3)&#xD;
&#xD;
          -  active chemotherapy within the 3 months preceding eligibility or&#xD;
&#xD;
          -  diagnosis of cystic fibrosis.&#xD;
&#xD;
        These criteria all represent conditions in which antibiotic use is much less likely to be&#xD;
        decreased regardless of the results of a biomarker and are consistent with exclusion&#xD;
        criteria used in past studies of the impact of biomarkers.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ebbing Lautenbach, MD,MPH,MSCE</last_name>
    <role>Principal Investigator</role>
    <affiliation>Univeristy of Pennsylvania</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital of the University of Pennsylvania - Medical Intensive Care Unit</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>February 3, 2014</study_first_submitted>
  <study_first_submitted_qc>July 31, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 1, 2014</study_first_posted>
  <last_update_submitted>March 6, 2023</last_update_submitted>
  <last_update_submitted_qc>March 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Sepsis</keyword>
  <keyword>Systemic Inflammatory Response Syndrome (SIRS)</keyword>
  <keyword>Antibiotic use</keyword>
  <keyword>Intensive Care Unit</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sepsis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02207114
org study id: 813623
nct id: NCT02207114
lead sponsor: 
has dmc: Yes
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Duration of antibiotic therapy started upon enrollment for presumed sepsis
time frame: Two years
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.
measure: Subject's Final Disposition
time frame: Participants will be followed for the duration of hospital stay, an expected average of 6 days
description: This includes assessing ICU mortality, hospital mortality, or hospital discharge as an ultimate outcome.
measure: Length of stay
time frame: Participants will be followed for the duration of hospital stay, an expected average of 6 days
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.
measure: Clinical Cure
time frame: Participants will be followed for the duration of hospital stay, an expected average of 6 days
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.
arm group label: Observational
arm group type: No Intervention
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 group label: Biomarker Algorithm Intervention
arm group type: Experimental
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: Biomarker Algorithm 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.
arm group label: Biomarker Algorithm Intervention
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Ebbing Lautenbach, MD,MPH,MSCE
role: Principal Investigator
affiliation: Univeristy of Pennsylvania
facility: 
country: United States
responsible party type: Sponsor
mesh term: Sepsis
sharing ipd: No