<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/NCT02212808</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00052362</org_study_id>
    <secondary_id>1UM1AI104681-01</secondary_id>
    <nct_id>NCT02212808</nct_id>
  </id_info>
  <brief_title>Antimicrobial Stewardship in Community Hospitals</brief_title>
  <official_title>A Multicenter, 3-Stage Cluster Randomized Historically-Controlled Crossover Trial to Determine the Feasibility and Outcomes From Two Antimicrobial Stewardship Interventions in Community Hospitals</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The Infectious Diseases Society of America (IDSA) guidelines recommend two &quot;core&quot; strategies&#xD;
      for Antibiotic Stewardship (AS): 1) antimicrobial restriction and preauthorization and 2)&#xD;
      prospective audit with intervention and feedback. Community hospitals have limited or no&#xD;
      resources and staff dedicated to AS. Thus, understanding which of the core strategies is most&#xD;
      feasible and effective in this practice setting would assist in appropriate allocation of&#xD;
      limited resources. The purpose of this study is to evaluate the feasibility of implementing&#xD;
      antimicrobial restriction and preauthorization vs. post antibiotic prescription review in&#xD;
      resource-limited community hospitals.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a three-stage cluster randomized historically controlled crossover trial&#xD;
      designed to evaluate the feasibility of the implementation of two AS strategies. Four&#xD;
      community hospitals in the Duke Infection Control Outreach Network (DICON) will be recruited&#xD;
      for this study. Ideally, hospitals will have no teaching affiliation, bed size &lt;300, and no&#xD;
      existing antimicrobial formulary restriction and preauthorization or post-antibiotic&#xD;
      prescription review practices in place at study start.&#xD;
&#xD;
      Data will be obtained from the four community hospitals in three stages. In stage 1,&#xD;
      historical data from each hospital will be collected for the year prior to study initiation&#xD;
      from all participating hospitals. These data are used as a control representing current&#xD;
      practice. In stage 2, the four hospitals will be divided into two pairs based upon bed size.&#xD;
      One hospital from each pair will be randomly assigned to a six-month period of antimicrobial&#xD;
      restriction and preauthorization (Strategy 1; stage 2) followed by a six-month period of&#xD;
      post-antibiotic prescription review (Strategy 2; stage 3). The other two hospitals will&#xD;
      undergo Strategy 2 in stage 2 followed by Strategy 1 in stage 3 to help alleviate the concern&#xD;
      for seasonal/temporal effects when comparing the strategies to each other. A one-month wash&#xD;
      out will be performed between each stage. Three antibiotics will be specifically targeted for&#xD;
      intervention: anti-pseudomonal carbapenem of choice at the study hospital, vancomycin, and&#xD;
      piperacillin-tazobactam. Utilization of alternative antimicrobials, including&#xD;
      fluoroquinolones, cephalosporins, and anti-methicillin resistant Staphylococcus aureus (anti&#xD;
      MRSA) systemic antimicrobials (e.g., nafcillin, daptomycin, linezolid, ceftaroline,&#xD;
      clindamycin, and trimethoprim-sulfamethoxazole (TMP-SMX)) will also be collected. All study&#xD;
      hospitals will have electronic systems that track antimicrobial prescriptions through orders,&#xD;
      electronic medication administration records (eMAR), bar-coded medication administration&#xD;
      (BCMA), or dispensing data.&#xD;
&#xD;
      Hospitals will have dedicated clinical pharmacist time for preauthorization or&#xD;
      post-antibiotic review for the three targeted antibiotics in each arm of the study.&#xD;
      Pharmacists (PharmDs) at each site will receive standardized training by study personnel in&#xD;
      order to address common questions and anticipated arguments, and to establish a robust&#xD;
      knowledge base regarding the targeted antimicrobials (anti-pseudomonal carbapenem of choice&#xD;
      at the study hospital, vancomycin, and piperacillin-tazobactam). They will also be trained in&#xD;
      conflict management.&#xD;
&#xD;
      Study personnel will provide suggested criteria for appropriate use of each targeted drug.&#xD;
      Hospital P&amp;T committees will review, edit (if desired), and approve hospital-specific&#xD;
      protocols for appropriate use criteria for each study drug. Pharmacists will be provided with&#xD;
      specific clinical pathways for urinary tract infections (UTIs), community-acquired pneumonia&#xD;
      (CAP), healthcare-associated pneumonia (HCAP), bacteremia, and &quot;other&quot; uses of targeted&#xD;
      antimicrobial. Clinical pathways will be developed jointly by study personnel and based on&#xD;
      Centers for Disease Control and Prevention pilot projects. Clinical pharmacists will&#xD;
      determine appropriateness of therapy based on study clinical pathways, their baseline&#xD;
      knowledge, and acquired knowledge derived by training from study personnel. Time spent&#xD;
      performing the two stewardship strategies will be supported by grant funds. The designated&#xD;
      pharmacist will be involved in two critical components of the protocol: a) completing the&#xD;
      intervention and b) documenting the outcome of the intervention.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>May 2014</start_date>
  <completion_date type="Actual">December 2015</completion_date>
  <primary_completion_date type="Actual">November 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>Crossover Assignment</intervention_model>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Feasibility 1 - Intervention Approval</measure>
    <time_frame>Prior to implementation, estimated length of 3 months up to 6 months</time_frame>
    <description>To evaluate administrative steps required for protocol approval of two stewardship intervention strategies at study hospitals.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Feasibility 2 - PharmD training</measure>
    <time_frame>Prior to implementation, estimated length of 1 months up to 2 months</time_frame>
    <description>To evaluate the steps required for training of local PharmD(s) to administer the two stewardship strategies.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Feasibility 3 - PharmD Time</measure>
    <time_frame>Day of Intervention, expected length of 20 hours per week up to 52 weeks</time_frame>
    <description>To estimate and compare the time required of the pharmacist to administer the different strategies.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Feasibility 4 - Resource Utilization</measure>
    <time_frame>During hospitalization, an expected length of 14 days, up to 30 days</time_frame>
    <description>To estimate and compare the resource utilization of each strategy, including pharmacist time and cost of antibiotics.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Antimicrobial utilization - Days of Therapy</measure>
    <time_frame>During Hospitalization, an expected length of 14 days, up to 30 days</time_frame>
    <description>To compare the total days of therapy of targeted and alternative antibiotics between each strategy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Outcomes</measure>
    <time_frame>During Hospitalization, an expected length of 14 days, up to 30 days</time_frame>
    <description>To compare patient-specific outcomes between each strategy including but not limited to total hospital days, death and ICU admission</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacist/Physician Perceptions</measure>
    <time_frame>Within 1 month of completion of intervention arm</time_frame>
    <description>To compare the prescriber and pharmacist perceptions of the two stewardship strategies</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">3972</enrollment>
  <condition>Antibiotic Stewardship in Community Hospitals</condition>
  <arm_group>
    <arm_group_label>Antimicrobial restriction</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All prescriptions for targeted antibiotics will require phone approval by the trained PharmD during this arm. Prescribers will be instructed to contact the pharmacist via pager or phone call to discuss the patient details and the rationale for the desired antimicrobial. The pharmacist will then decide if the targeted antibiotic is approved or denied. If the pharmacist denies the use of the targeted antibiotic, the pharmacist will provide recommendations for alternative antibiotics for the specific clinical scenario.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Post-antimicrobial prescription review</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All prescriptions for targeted antibiotics will be reviewed by the study pharmacist approximately 72 hours after initially written. The pharmacists will review a list of patients receiving the targeted antibiotics on a daily basis to identify patients who have received one or more targeted antibiotics for 72 hours (± 24 hours). The pharmacist will review and document the patient's current symptoms, pertinent clinical data, and the indication for the targeted antibiotic documented in the chart. Based on this review, the pharmacist will decide if the targeted antibiotic is necessary and/or if it needs to be modified. If a change is recommended, the pharmacist will then contact the prescriber to discuss the pharmacist's recommendations.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Antimicrobial restriction</intervention_name>
    <description>All prescriptions for targeted antibiotics will require phone approval by the trained PharmD during this arm. Prescribers will be instructed to contact the pharmacist via pager or phone call to discuss the patient details and the rationale for the desired antimicrobial. The pharmacist will then decide if the targeted antibiotic is approved or denied. If the pharmacist denies the use of the targeted antibiotic, the pharmacist will provide recommendations for alternative antibiotics for the specific clinical scenario. The pharmacist will document this interaction in the REDCap database.</description>
    <arm_group_label>Antimicrobial restriction</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Post-antimicrobial prescription review</intervention_name>
    <description>All prescriptions for targeted antibiotics will be reviewed by the study pharmacist approximately 72 hours after initially written. The pharmacist will review and document the patient's current symptoms, pertinent clinical data, and the indication for the targeted antibiotic documented in the chart. Based on this review, the pharmacist will decide if the targeted antibiotic is necessary and/or if it needs to be modified. If a change is recommended, the pharmacist will then contact the prescriber to discuss the pharmacist's recommendations. The interaction will be documented in the REDCap database.</description>
    <arm_group_label>Post-antimicrobial prescription review</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        -All adult and pediatric patients admitted to the study hospital who are prescribed&#xD;
        targeted or alternative antimicrobial agent(s) will have data collected from their medical&#xD;
        records.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any patient not meeting the criteria above will be excluded.&#xD;
&#xD;
          -  Patients who receive &lt; 24 hours of surgical prophylaxis with a targeted or alternative&#xD;
             antimicrobial will be excluded.&#xD;
&#xD;
          -  Finally, any patient followed by an Infectious Disease consultant will be excluded.&#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>Deverick J Anderson, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <verification_date>March 2016</verification_date>
  <study_first_submitted>August 1, 2014</study_first_submitted>
  <study_first_submitted_qc>August 6, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 8, 2014</study_first_posted>
  <last_update_submitted>March 21, 2016</last_update_submitted>
  <last_update_submitted_qc>March 21, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 22, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cluster-randomized crossover trial</keyword>
  <keyword>Antimicrobial stewardship</keyword>
  <keyword>Community hospitals</keyword>
  <keyword>Feasibility</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anti-Infective Agents</mesh_term>
    <mesh_term>Anti-Bacterial Agents</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02212808
org study id: Pro00052362
secondary id: 1UM1AI104681-01
nct id: NCT02212808
lead sponsor: 
collaborator: 
has dmc: Yes
The Infectious Diseases Society of America (IDSA) guidelines recommend two "core" strategies
      for Antibiotic Stewardship (AS): 1) antimicrobial restriction and preauthorization and 2)
      prospective audit with intervention and feedback. Community hospitals have limited or no
      resources and staff dedicated to AS. Thus, understanding which of the core strategies is most
      feasible and effective in this practice setting would assist in appropriate allocation of
      limited resources. The purpose of this study is to evaluate the feasibility of implementing
      antimicrobial restriction and preauthorization vs. post antibiotic prescription review in
      resource-limited community hospitals.
This study is a three-stage cluster randomized historically controlled crossover trial
      designed to evaluate the feasibility of the implementation of two AS strategies. Four
      community hospitals in the Duke Infection Control Outreach Network (DICON) will be recruited
      for this study. Ideally, hospitals will have no teaching affiliation, bed size <300, and no
      existing antimicrobial formulary restriction and preauthorization or post-antibiotic
      prescription review practices in place at study start.

      Data will be obtained from the four community hospitals in three stages. In stage 1,
      historical data from each hospital will be collected for the year prior to study initiation
      from all participating hospitals. These data are used as a control representing current
      practice. In stage 2, the four hospitals will be divided into two pairs based upon bed size.
      One hospital from each pair will be randomly assigned to a six-month period of antimicrobial
      restriction and preauthorization (Strategy 1; stage 2) followed by a six-month period of
      post-antibiotic prescription review (Strategy 2; stage 3). The other two hospitals will
      undergo Strategy 2 in stage 2 followed by Strategy 1 in stage 3 to help alleviate the concern
      for seasonal/temporal effects when comparing the strategies to each other. A one-month wash
      out will be performed between each stage. Three antibiotics will be specifically targeted for
      intervention: anti-pseudomonal carbapenem of choice at the study hospital, vancomycin, and
      piperacillin-tazobactam. Utilization of alternative antimicrobials, including
      fluoroquinolones, cephalosporins, and anti-methicillin resistant Staphylococcus aureus (anti
      MRSA) systemic antimicrobials (e.g., nafcillin, daptomycin, linezolid, ceftaroline,
      clindamycin, and trimethoprim-sulfamethoxazole (TMP-SMX)) will also be collected. All study
      hospitals will have electronic systems that track antimicrobial prescriptions through orders,
      electronic medication administration records (eMAR), bar-coded medication administration
      (BCMA), or dispensing data.

      Hospitals will have dedicated clinical pharmacist time for preauthorization or
      post-antibiotic review for the three targeted antibiotics in each arm of the study.
      Pharmacists (PharmDs) at each site will receive standardized training by study personnel in
      order to address common questions and anticipated arguments, and to establish a robust
      knowledge base regarding the targeted antimicrobials (anti-pseudomonal carbapenem of choice
      at the study hospital, vancomycin, and piperacillin-tazobactam). They will also be trained in
      conflict management.

      Study personnel will provide suggested criteria for appropriate use of each targeted drug.
      Hospital P&T committees will review, edit (if desired), and approve hospital-specific
      protocols for appropriate use criteria for each study drug. Pharmacists will be provided with
      specific clinical pathways for urinary tract infections (UTIs), community-acquired pneumonia
      (CAP), healthcare-associated pneumonia (HCAP), bacteremia, and "other" uses of targeted
      antimicrobial. Clinical pathways will be developed jointly by study personnel and based on
      Centers for Disease Control and Prevention pilot projects. Clinical pharmacists will
      determine appropriateness of therapy based on study clinical pathways, their baseline
      knowledge, and acquired knowledge derived by training from study personnel. Time spent
      performing the two stewardship strategies will be supported by grant funds. The designated
      pharmacist will be involved in two critical components of the protocol: a) completing the
      intervention and b) documenting the outcome of the intervention.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Health Services Research
masking: None (Open Label)
measure: Feasibility 1 - Intervention Approval
time frame: Prior to implementation, estimated length of 3 months up to 6 months
description: To evaluate administrative steps required for protocol approval of two stewardship intervention strategies at study hospitals.
measure: Feasibility 2 - PharmD training
time frame: Prior to implementation, estimated length of 1 months up to 2 months
description: To evaluate the steps required for training of local PharmD(s) to administer the two stewardship strategies.
measure: Feasibility 3 - PharmD Time
time frame: Day of Intervention, expected length of 20 hours per week up to 52 weeks
description: To estimate and compare the time required of the pharmacist to administer the different strategies.
measure: Feasibility 4 - Resource Utilization
time frame: During hospitalization, an expected length of 14 days, up to 30 days
description: To estimate and compare the resource utilization of each strategy, including pharmacist time and cost of antibiotics.
measure: Antimicrobial utilization - Days of Therapy
time frame: During Hospitalization, an expected length of 14 days, up to 30 days
description: To compare the total days of therapy of targeted and alternative antibiotics between each strategy.
measure: Patient Outcomes
time frame: During Hospitalization, an expected length of 14 days, up to 30 days
description: To compare patient-specific outcomes between each strategy including but not limited to total hospital days, death and ICU admission
measure: Pharmacist/Physician Perceptions
time frame: Within 1 month of completion of intervention arm
description: To compare the prescriber and pharmacist perceptions of the two stewardship strategies
arm group label: Antimicrobial restriction
arm group type: Experimental
description: All prescriptions for targeted antibiotics will require phone approval by the trained PharmD during this arm. Prescribers will be instructed to contact the pharmacist via pager or phone call to discuss the patient details and the rationale for the desired antimicrobial. The pharmacist will then decide if the targeted antibiotic is approved or denied. If the pharmacist denies the use of the targeted antibiotic, the pharmacist will provide recommendations for alternative antibiotics for the specific clinical scenario.
arm group label: Post-antimicrobial prescription review
arm group type: Experimental
description: All prescriptions for targeted antibiotics will be reviewed by the study pharmacist approximately 72 hours after initially written. The pharmacists will review a list of patients receiving the targeted antibiotics on a daily basis to identify patients who have received one or more targeted antibiotics for 72 hours (± 24 hours). The pharmacist will review and document the patient's current symptoms, pertinent clinical data, and the indication for the targeted antibiotic documented in the chart. Based on this review, the pharmacist will decide if the targeted antibiotic is necessary and/or if it needs to be modified. If a change is recommended, the pharmacist will then contact the prescriber to discuss the pharmacist's recommendations.
intervention type: Other
intervention name: Antimicrobial restriction
description: All prescriptions for targeted antibiotics will require phone approval by the trained PharmD during this arm. Prescribers will be instructed to contact the pharmacist via pager or phone call to discuss the patient details and the rationale for the desired antimicrobial. The pharmacist will then decide if the targeted antibiotic is approved or denied. If the pharmacist denies the use of the targeted antibiotic, the pharmacist will provide recommendations for alternative antibiotics for the specific clinical scenario. The pharmacist will document this interaction in the REDCap database.
arm group label: Antimicrobial restriction
intervention type: Other
intervention name: Post-antimicrobial prescription review
description: All prescriptions for targeted antibiotics will be reviewed by the study pharmacist approximately 72 hours after initially written. The pharmacist will review and document the patient's current symptoms, pertinent clinical data, and the indication for the targeted antibiotic documented in the chart. Based on this review, the pharmacist will decide if the targeted antibiotic is necessary and/or if it needs to be modified. If a change is recommended, the pharmacist will then contact the prescriber to discuss the pharmacist's recommendations. The interaction will be documented in the REDCap database.
arm group label: Post-antimicrobial prescription review
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Deverick J Anderson, MD, MPH
role: Principal Investigator
affiliation: Duke University
responsible party type: Sponsor
mesh term: Anti-Infective Agents
mesh term: Anti-Bacterial Agents