<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/NCT03245879</url>
  </required_header>
  <id_info>
    <org_study_id>1024823</org_study_id>
    <nct_id>NCT03245879</nct_id>
  </id_info>
  <brief_title>Antibiotic Stewardship in Small Hospitals</brief_title>
  <acronym>SCORE</acronym>
  <official_title>Impact of Implementing Antibiotic Stewardship Programs in 15 Small Hospitals: A Cluster-Randomized Trial Intervention</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Intermountain Health Care, Inc.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Intermountain Health Care, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Core elements of effective antibiotic stewardship programs (ASPs) have been identified and&#xD;
      evidence-based guidelines have been developed for implementation. The majority of the&#xD;
      evidence used for these guidelines are from published studies on the effectiveness of ASPs in&#xD;
      large academic or large community hospitals. A significant portion of healthcare in the&#xD;
      United States, however, takes place in small hospitals. In 2015, 73% of US hospitals had &lt;&#xD;
      200 beds (4,057 hospitals) and accounted for 29% of all US inpatient bed days. Limited&#xD;
      studies on the effectiveness of antibiotic stewardship implementation have been performed in&#xD;
      hospitals with &lt; 200 beds. Antibiotic use rates and selection patterns in these small&#xD;
      hospitals are similar to that of large hospitals and the majority of small hospitals lack&#xD;
      formal ASP that meet the CDC's core elements. The objective of this real-world implementation&#xD;
      study was to assess the effectiveness of three ASP strategies of escalating intensity&#xD;
      designed specifically for small hospitals within a vertically integrated healthcare delivery&#xD;
      system.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators designed a clustered randomized controlled intervention to evaluate 3&#xD;
      antibiotic stewardship strategies designed for small hospitals. Each hospital was randomized&#xD;
      to one of three ASP interventions with increasing levels of intensity and intervention&#xD;
      (Programs 1, 2, 3). The investigators felt that clinical equipoise about the effect of ASPs&#xD;
      did not exist and randomizing to a no-intervention group was unacceptable. Antibiotic use was&#xD;
      compared within each group before and after the intervention. In keeping with other&#xD;
      real-world implementation studies, secondary analyses were planned to include an interrupted&#xD;
      time series design to evaluate the impact of each strategy. Randomization of hospitals was&#xD;
      stratified based on patient volume. Hospital administration and clinical leadership were not&#xD;
      blinded to which ASP program they were randomly assigned to, but there were no public&#xD;
      announcements. The intervention started March 2014 and ended June 2015.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 2013</start_date>
  <completion_date type="Actual">June 2015</completion_date>
  <primary_completion_date type="Actual">June 2015</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>Health Services Research</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Total antibiotic use</measure>
    <time_frame>Total antibiotic use during the 15 months of Intervention (April 1, 2014 through June 30th 2015) was compared to the antibiotic use during the 12 month baseline period (Jan 1 through Dec 31 2013).</time_frame>
    <description>Evaluated change in total antibiotic use between the baseline and intervention periods while accounting for the cluster randomized design.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Broad spectrum antibiotic use</measure>
    <time_frame>Broad spectrum antibiotic use during the 15 months of Intervention (April 1, 2014 through June 30th 2015) was compared to the broad spectrum antibiotic use during the 12 month baseline period (Jan 1 through Dec 31 2013).</time_frame>
    <description>Evaluated change in broad spectrum antibiotic use between the baseline and intervention periods</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Restricted antibiotic use</measure>
    <time_frame>Restricted antibiotic use during the 15 months of Intervention (April 1, 2014 through June 30th 2015) was compared to the restricted antibiotic use during the 12 month baseline period (Jan 1 through Dec 31 2013).</time_frame>
    <description>Evaluated change in restricted antibiotic use between the baseline and intervention periods</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>30-day readmission</measure>
    <time_frame>30-day readmission rate during the 15 months of Intervention (April 1, 2014 through June 30th 2015) was compared to the 30-day readmission rate during the 12 month baseline period (Jan 1 through Dec 31 2013).</time_frame>
    <description>Evaluated change in 30 day readmission rates between the baseline and intervention periods</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>30-day mortality</measure>
    <time_frame>30-day mortality rate during the 15 months of Intervention (April 1, 2014 through June 30th 2015) was compared to the 30-day mortality rate during the 12 month baseline period (Jan 1 through Dec 31 2013).</time_frame>
    <description>Evaluated change in 30 day mortality rates between the baseline and intervention periods</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital length of stay</measure>
    <time_frame>Average hospital length of stay during the 15 months of Intervention (April 1, 2014 through June 30th 2015) was compared to the average hospital length of stay during the 12 month baseline period (Jan 1 through Dec 31 2013).</time_frame>
    <description>Evaluated change in hospital length of stay between the baseline and intervention periods</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clostridium difficile</measure>
    <time_frame>C. difficile rate during the 15 months of Intervention (April 1, 2014 through June 30th 2015) was compared to the C. difficile rate during the 12 month baseline period (Jan 1 through Dec 31 2013).</time_frame>
    <description>Evaluated change in Clostridium difficile incidence between the baseline and intervention periods</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">30000</enrollment>
  <condition>Inappropriate Prescribing</condition>
  <condition>Antibiotic Stewardship</condition>
  <condition>Anti-Bacterial Agents</condition>
  <arm_group>
    <arm_group_label>Program 1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Implementation of a basic antibiotic stewardship program focusing on education, access to Infectious Diseases physicians, and availability of antibiotic use data.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Program 2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>This arm increases antibiotic stewardship education and interventions. Program 2 hospitals performed audit and feedback of pre-specified antibiotics and implemented locally controlled restrictions.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Program 3</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>This arm was the most intensive antibiotic stewardship intervention. It included signficant audit and feedback, ID controlled restrictions, and ID review of designated culture/lab results.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Program 1</intervention_name>
    <description>Program 1 hospitals received a basic curriculum and tools for implementation of basic antibiotic stewardship interventions. Hospitals required an indication for every antibiotic order. A daily email was sent to a designated email account when a patient had been on an antibiotic for &gt;48 hours. Curriculum included implementing antibiotic time-outs, IV to PO conversion, indications, evaluating for bug-drug mismatches, and recommendations on when to call the Infectious Diseases (ID) hotline. A daily antibiotic stewardship check list was created. All materials were provided to all pharmacists and remained on-site. Clinicians had access to an ID telephone hotline to answer clinical questions. Pharmacy directors and hospital leadership were provided a monthly, hospital-specific, antibiotic use dashboard. All pharmacy directors and staff received a monthly newsletter.</description>
    <arm_group_label>Program 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Program 2</intervention_name>
    <description>Program 2 hospitals received all the interventions of Program 1. In addition, Program 2 hospitals received more intense antibiotic stewardship education. Educational topics included audit and feedback, antibiotic de-escalation, the need for antibiotics targeting anaerobic bacteria, antibiotic allergy verification, and antibiotic restrictions. Pharmacists in Program 2 hospitals reviewed patients on vancomycin, piperacillin/tazobactam, imipenem, meropenem, and cefepime. For patients receiving one of these antibiotics, pharmacists reviewed the patients' microbiology data to identify opportunities for antibiotic de-escalation, IV to PO conversion, bug-drug mismatches, and/or indications for calling the ID hotline. Program 2 hospitals also restricted daptomycin, linezolid, imipenem, meropenem, ceftaroline, tigecycline, and all mold active antifungals. In Program 2 hospitals, the local pharmacy staff pre-authorized restricted antibiotics based on defined criteria.</description>
    <arm_group_label>Program 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Program 3</intervention_name>
    <description>Program 3 hospitals received all the interventions of Program 1 and Program 2. In addition, pharmacists in program 3 hospitals reviewed an expanded list of antibiotics for audit and feedback. These antibiotics included: Vancomycin, piperacillin/tazobactam, imipenem, meropenem, cefepime, ertapenem, aminoglycosides, ceftriaxone, and fluoroquinolones. Program 3 hospitals implemented the same antibiotic restrictions as Program 2 but ID pharmacists controlled pre-authorization of restricted antibiotics. In addition, an ID physician reviewed pre-specified positive cultures (e.g. all positive blood cultures, cultures with highly resistant Enterobacteraciae) and contacted providers with recommendations as needed. ID physician review occurred Monday through Friday and alerts were batched daily at 6am.</description>
    <arm_group_label>Program 3</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Intermountain Healthcare acute care hospital with &lt; 200 licensed beds&#xD;
&#xD;
          -  No formal antibiotic stewardship program in place&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        -All Intermountain Healthcare specialty hospitals, regardless of bed size&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <link>
    <url>http://idsa.confex.com/idsa/2016/webprogram/Paper57499.html</url>
    <description>IDWeek 2016 SHEA Featured Oral Abstract</description>
  </link>
  <reference>
    <citation>Stenehjem E, Hersh AL, Sheng X, Jones P, Buckel WR, Lloyd JF, Howe S, Evans RS, Greene T, Pavia AT. Antibiotic Use in Small Community Hospitals. Clin Infect Dis. 2016 Nov 15;63(10):1273-1280. doi: 10.1093/cid/ciw588. Epub 2016 Sep 30.</citation>
    <PMID>27694483</PMID>
  </reference>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 3, 2017</study_first_submitted>
  <study_first_submitted_qc>August 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2017</study_first_posted>
  <last_update_submitted>August 7, 2017</last_update_submitted>
  <last_update_submitted_qc>August 7, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 10, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Intermountain Health Care, Inc.</investigator_affiliation>
    <investigator_full_name>Eddie Stenehjem</investigator_full_name>
    <investigator_title>Associate Professor of Medicine</investigator_title>
  </responsible_party>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>N/A. No individual patient level data available.</ipd_description>
  </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/NCT03245879
org study id: 1024823
nct id: NCT03245879
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Core elements of effective antibiotic stewardship programs (ASPs) have been identified and
      evidence-based guidelines have been developed for implementation. The majority of the
      evidence used for these guidelines are from published studies on the effectiveness of ASPs in
      large academic or large community hospitals. A significant portion of healthcare in the
      United States, however, takes place in small hospitals. In 2015, 73% of US hospitals had <
      200 beds (4,057 hospitals) and accounted for 29% of all US inpatient bed days. Limited
      studies on the effectiveness of antibiotic stewardship implementation have been performed in
      hospitals with < 200 beds. Antibiotic use rates and selection patterns in these small
      hospitals are similar to that of large hospitals and the majority of small hospitals lack
      formal ASP that meet the CDC's core elements. The objective of this real-world implementation
      study was to assess the effectiveness of three ASP strategies of escalating intensity
      designed specifically for small hospitals within a vertically integrated healthcare delivery
      system.
The investigators designed a clustered randomized controlled intervention to evaluate 3
      antibiotic stewardship strategies designed for small hospitals. Each hospital was randomized
      to one of three ASP interventions with increasing levels of intensity and intervention
      (Programs 1, 2, 3). The investigators felt that clinical equipoise about the effect of ASPs
      did not exist and randomizing to a no-intervention group was unacceptable. Antibiotic use was
      compared within each group before and after the intervention. In keeping with other
      real-world implementation studies, secondary analyses were planned to include an interrupted
      time series design to evaluate the impact of each strategy. Randomization of hospitals was
      stratified based on patient volume. Hospital administration and clinical leadership were not
      blinded to which ASP program they were randomly assigned to, but there were no public
      announcements. The intervention started March 2014 and ended June 2015.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Health Services Research
masking: None (Open Label)
measure: Total antibiotic use
time frame: Total antibiotic use during the 15 months of Intervention (April 1, 2014 through June 30th 2015) was compared to the antibiotic use during the 12 month baseline period (Jan 1 through Dec 31 2013).
description: Evaluated change in total antibiotic use between the baseline and intervention periods while accounting for the cluster randomized design.
measure: Broad spectrum antibiotic use
time frame: Broad spectrum antibiotic use during the 15 months of Intervention (April 1, 2014 through June 30th 2015) was compared to the broad spectrum antibiotic use during the 12 month baseline period (Jan 1 through Dec 31 2013).
description: Evaluated change in broad spectrum antibiotic use between the baseline and intervention periods
measure: Restricted antibiotic use
time frame: Restricted antibiotic use during the 15 months of Intervention (April 1, 2014 through June 30th 2015) was compared to the restricted antibiotic use during the 12 month baseline period (Jan 1 through Dec 31 2013).
description: Evaluated change in restricted antibiotic use between the baseline and intervention periods
measure: 30-day readmission
time frame: 30-day readmission rate during the 15 months of Intervention (April 1, 2014 through June 30th 2015) was compared to the 30-day readmission rate during the 12 month baseline period (Jan 1 through Dec 31 2013).
description: Evaluated change in 30 day readmission rates between the baseline and intervention periods
measure: 30-day mortality
time frame: 30-day mortality rate during the 15 months of Intervention (April 1, 2014 through June 30th 2015) was compared to the 30-day mortality rate during the 12 month baseline period (Jan 1 through Dec 31 2013).
description: Evaluated change in 30 day mortality rates between the baseline and intervention periods
measure: Hospital length of stay
time frame: Average hospital length of stay during the 15 months of Intervention (April 1, 2014 through June 30th 2015) was compared to the average hospital length of stay during the 12 month baseline period (Jan 1 through Dec 31 2013).
description: Evaluated change in hospital length of stay between the baseline and intervention periods
measure: Clostridium difficile
time frame: C. difficile rate during the 15 months of Intervention (April 1, 2014 through June 30th 2015) was compared to the C. difficile rate during the 12 month baseline period (Jan 1 through Dec 31 2013).
description: Evaluated change in Clostridium difficile incidence between the baseline and intervention periods
arm group label: Program 1
arm group type: Active Comparator
description: Implementation of a basic antibiotic stewardship program focusing on education, access to Infectious Diseases physicians, and availability of antibiotic use data.
arm group label: Program 2
arm group type: Active Comparator
description: This arm increases antibiotic stewardship education and interventions. Program 2 hospitals performed audit and feedback of pre-specified antibiotics and implemented locally controlled restrictions.
arm group label: Program 3
arm group type: Active Comparator
description: This arm was the most intensive antibiotic stewardship intervention. It included signficant audit and feedback, ID controlled restrictions, and ID review of designated culture/lab results.
intervention type: Behavioral
intervention name: Program 1
description: Program 1 hospitals received a basic curriculum and tools for implementation of basic antibiotic stewardship interventions. Hospitals required an indication for every antibiotic order. A daily email was sent to a designated email account when a patient had been on an antibiotic for >48 hours. Curriculum included implementing antibiotic time-outs, IV to PO conversion, indications, evaluating for bug-drug mismatches, and recommendations on when to call the Infectious Diseases (ID) hotline. A daily antibiotic stewardship check list was created. All materials were provided to all pharmacists and remained on-site. Clinicians had access to an ID telephone hotline to answer clinical questions. Pharmacy directors and hospital leadership were provided a monthly, hospital-specific, antibiotic use dashboard. All pharmacy directors and staff received a monthly newsletter.
arm group label: Program 1
intervention type: Behavioral
intervention name: Program 2
description: Program 2 hospitals received all the interventions of Program 1. In addition, Program 2 hospitals received more intense antibiotic stewardship education. Educational topics included audit and feedback, antibiotic de-escalation, the need for antibiotics targeting anaerobic bacteria, antibiotic allergy verification, and antibiotic restrictions. Pharmacists in Program 2 hospitals reviewed patients on vancomycin, piperacillin/tazobactam, imipenem, meropenem, and cefepime. For patients receiving one of these antibiotics, pharmacists reviewed the patients' microbiology data to identify opportunities for antibiotic de-escalation, IV to PO conversion, bug-drug mismatches, and/or indications for calling the ID hotline. Program 2 hospitals also restricted daptomycin, linezolid, imipenem, meropenem, ceftaroline, tigecycline, and all mold active antifungals. In Program 2 hospitals, the local pharmacy staff pre-authorized restricted antibiotics based on defined criteria.
arm group label: Program 2
intervention type: Behavioral
intervention name: Program 3
description: Program 3 hospitals received all the interventions of Program 1 and Program 2. In addition, pharmacists in program 3 hospitals reviewed an expanded list of antibiotics for audit and feedback. These antibiotics included: Vancomycin, piperacillin/tazobactam, imipenem, meropenem, cefepime, ertapenem, aminoglycosides, ceftriaxone, and fluoroquinolones. Program 3 hospitals implemented the same antibiotic restrictions as Program 2 but ID pharmacists controlled pre-authorization of restricted antibiotics. In addition, an ID physician reviewed pre-specified positive cultures (e.g. all positive blood cultures, cultures with highly resistant Enterobacteraciae) and contacted providers with recommendations as needed. ID physician review occurred Monday through Friday and alerts were batched daily at 6am.
arm group label: Program 3
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
url: http://idsa.confex.com/idsa/2016/webprogram/Paper57499.html
description: IDWeek 2016 SHEA Featured Oral Abstract
citation: Stenehjem E, Hersh AL, Sheng X, Jones P, Buckel WR, Lloyd JF, Howe S, Evans RS, Greene T, Pavia AT. Antibiotic Use in Small Community Hospitals. Clin Infect Dis. 2016 Nov 15;63(10):1273-1280. doi: 10.1093/cid/ciw588. Epub 2016 Sep 30.
PMID: 27694483
responsible party type: Principal Investigator
investigator affiliation: Intermountain Health Care, Inc.
investigator full name: Eddie Stenehjem
investigator title: Associate Professor of Medicine
sharing ipd: No
ipd description: N/A. No individual patient level data available.