<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/NCT04495946</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00036873</org_study_id>
    <secondary_id>R01NR018434</secondary_id>
    <nct_id>NCT04495946</nct_id>
  </id_info>
  <brief_title>Implementation and Effectiveness of Engagement and Collaborative Management to Proactively Advance Sepsis Survivorship</brief_title>
  <acronym>ENCOMPASS</acronym>
  <official_title>Implementation and Effectiveness of Engagement and Collaborative Management to Proactively Advance Sepsis Survivorship: A Hybrid Effectiveness-Implementation Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wake Forest University Health Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Nursing Research (NINR)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Wake Forest University Health Sciences</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The purpose of this study is to evaluate if implementation of the Sepsis Transition and&#xD;
      Recovery (STAR) program within a large healthcare system will improve outcomes for high-risk&#xD;
      patients with suspected sepsis, while concurrently examining contextual factors related to&#xD;
      STAR program delivery within routine care to generate knowledge of best practices for&#xD;
      implementation and dissemination of post sepsis transitions of care. To address persistent&#xD;
      morbidity and mortality for sepsis survivors, Atrium Health developed the Sepsis Treatment&#xD;
      and Recovery (STAR) program which uses a nurse navigator to deliver a bundle of best-practice&#xD;
      care elements for the delivery of longitudinal post-sepsis care for up to 90 days. These care&#xD;
      elements are directed towards the specific challenges and sequelae following a sepsis&#xD;
      hospitalization and include: 1) identification and treatment of new physical, mental, and&#xD;
      cognitive deficits; 2) review and adjustment of medications; 3) surveillance of treatable&#xD;
      conditions that commonly lead to poor outcomes including chronic conditions that may&#xD;
      de-stabilize during sepsis and recovery; and 4) focus on palliative care when appropriate.&#xD;
      ENCOMPASS (Engagement and Collaborative Management to Proactively Advance Sepsis&#xD;
      Survivorship) is an effectiveness-implementation hybrid type I trial, with the evaluation&#xD;
      designed as a two-arm, pragmatic, stepped-wedge cluster randomized controlled trial conducted&#xD;
      at eight regional hospitals in which each participating hospital begins in a usual care&#xD;
      control phase and transitions to the STAR program intervention in a randomly assigned&#xD;
      sequence. Patients are allocated to receive the treatment condition (i.e., usual care or&#xD;
      STAR) assigned to their admission hospital at time of enrollment. ENCOMPASS will test the&#xD;
      hypothesis that patients who receive care through the STAR program will have reduced&#xD;
      mortality and hospital readmission assessed 90 days post index hospital discharge compared to&#xD;
      patients who receive usual care.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      BACKGROUND&#xD;
&#xD;
      Sepsis is a common and life-threatening condition defined by organ dysfunction due to a&#xD;
      dysregulated response to infection (Fleischmann, 2016). Aggressive early sepsis&#xD;
      identification and treatment initiatives have decreased hospital mortality for patients with&#xD;
      sepsis (Rhodes, 2017; Kaukonen, 2014). However, sepsis survivors continue to face challenges&#xD;
      after the acute illness episode, experiencing new functional, cognitive, and psychological&#xD;
      deficits, and high rates of hospital readmission and mortality in the 90-days after hospital&#xD;
      discharge (Iwashyna, 2010; Borges, 2015; Annane, 2015; Prescott, 2015; Mayr, 2017). To&#xD;
      address persistent morbidity and mortality for sepsis survivors, Atrium Health developed the&#xD;
      Sepsis Treatment and Recovery (STAR) program which uses a nurse navigator to deliver a bundle&#xD;
      of best-practice care elements for the delivery of longitudinal post-sepsis care for up to 90&#xD;
      days. These care elements are directed towards the specific challenges and sequelae following&#xD;
      a sepsis hospitalization and include: 1) identification and treatment of new physical,&#xD;
      mental, and cognitive deficits; 2) review and adjustment of medications; 3) surveillance of&#xD;
      treatable conditions that commonly lead to poor outcomes including chronic conditions that&#xD;
      may destabilize during sepsis and recovery; and 4) focus on palliative care when appropriate&#xD;
      (Prescott, 2018) These care elements have good face-validity and have shown to be associated&#xD;
      with improved outcomes for sepsis survivors in observational data (Taylor, 2020). However,&#xD;
      they are not widely applied in real-world settings for this vulnerable population, likely&#xD;
      hindered by a gap in understanding key contextual factors underlying how to best integrate&#xD;
      this bundle of care elements into the complex and fragmented post-discharge setting&#xD;
      (Brownson, 2012; Bodenheimer, 2008; Coleman, 2004; Kim, 2013)&#xD;
&#xD;
      RATIONALE&#xD;
&#xD;
      In randomized controlled trials (RCTs), successfully implemented care transition programs&#xD;
      using nurse navigators have been shown to reduce hospital readmission and costs. To better&#xD;
      enhance transitions of care for the highest risk, complex patients with suspected sepsis, the&#xD;
      investigators propose extending this evidence using a nurse-facilitated care transition&#xD;
      program for patients in the post-sepsis transition period to improve the implementation of&#xD;
      recommended care practices and bridge care gaps. This approach, called the Sepsis Transition&#xD;
      and Recovery (STAR) program, is the next step in the progression of the investigator team's&#xD;
      work on improving discharge transitions and sepsis processes of care. A key aspect of this&#xD;
      initiative includes the ability to identify sepsis survivors at the greatest risk for poor&#xD;
      outcomes. For example, one-quarter of sepsis survivors account for three-quarters of hospital&#xD;
      readmission and costs, indicating that identifying high-risk sepsis patients for targeted&#xD;
      facilitation of best-practice care could efficiently impact quality and cost.&#xD;
&#xD;
      The STAR program uses near real-time risk modeling to identify high-risk patients and a&#xD;
      centrally located nurse, virtually connected to participating hospitals, to coordinate the&#xD;
      application of evidence-based recommendations for post-sepsis care, overcome barriers to&#xD;
      recommended care, and bridge gaps in service that can serve as points of failure for complex&#xD;
      patients. During hospitalization, high-risk patients enter into a transition pathway&#xD;
      integrated within Atrium Health Hospital Medicine's Transition Services program and includes&#xD;
      the following core components: i) Introduction to STAR process prior to discharge (confirm&#xD;
      provider consults e.g., PT, ID, palliative); ii) Disease-specific education and discharge&#xD;
      &quot;playbook&quot;; iii) Virtual hospital follow-up evaluation within 48 hours including medication&#xD;
      reconciliation; iv) Second, post-acute virtual follow-up within 72-96 hours (symptom&#xD;
      monitoring, confirm provider follow-up); v) Weekly contact with STAR team; vi) Referral to&#xD;
      provider follow-up (e.g., primary care provider, transition clinic) as appropriate; vii)&#xD;
      Coordinated transition to the next appropriate care location after 90 days from time of&#xD;
      discharge. The STAR navigator also meets weekly with the Medical Director of the Atrium&#xD;
      Health Transition Services program who provides additional clinical oversight of ongoing&#xD;
      cases.&#xD;
&#xD;
      The ENCOMPASS (Engagement and Collaborative Management to Proactively Advance Sepsis&#xD;
      Survivorship) evaluation will examine if implementation of the STAR program within a large&#xD;
      healthcare system will improve outcomes for high-risk sepsis patients. This cluster&#xD;
      randomized program evaluation is designed to be a seamless part of routine care in a&#xD;
      real-world setting to generate knowledge of best practices for implementation and&#xD;
      dissemination of post-sepsis transitions of care.&#xD;
&#xD;
      INVESTIGATIONAL PLAN&#xD;
&#xD;
      Overall Study Design ENCOMPASS is an effectiveness-implementation hybrid type I trial. The&#xD;
      evaluation component is designed as a two-arm, pragmatic, stepped-wedge cluster randomized&#xD;
      controlled trial conducted at eight regional hospitals in which each participating hospital&#xD;
      begins in a usual care control phase and transitions to the STAR program intervention in a&#xD;
      randomly assigned sequence, with one of eight hospitals assigned to transition at each&#xD;
      four-month interval (i.e., step). During the time that a hospital is allocated to usual care,&#xD;
      all eligible patients will receive usual care. Once a hospital has been allocated to the STAR&#xD;
      arm, all eligible patients will receive STAR during their index hospitalization and extending&#xD;
      through 90 days from discharge or date of death. The ENCOMPASS trial will compare the&#xD;
      effectiveness of the Sepsis Transition And Recovery (STAR) program versus usual care on&#xD;
      post-sepsis care and patient outcomes. The STAR program is informed by existing evidence and&#xD;
      designed using the Chronic Care Model to increase best-practice adherence and care&#xD;
      coordination, resulting in improved transitions between hospitals and post-acute care during&#xD;
      sepsis recovery.&#xD;
&#xD;
      ENCOMPASS will test the STAR program intervention within the course of providing usual care&#xD;
      among a large and diverse population of post-sepsis patients admitted to eight hospitals&#xD;
      within Atrium Health, one of the largest, vertically integrated health systems in the US. The&#xD;
      eight acute care hospitals participating in this study use the same EHR, which connects&#xD;
      across all points of care, including outpatient practices, urgent care locations, emergency&#xD;
      departments and hospitals. Consistent with the pragmatic study design concept, eligibility&#xD;
      criteria are broad, the sample size is large and diverse, and study procedures are embedded&#xD;
      into the context of routine care. To be objective in patient selection and allow for program&#xD;
      evaluation, a data driven approach will be used to identify patients as eligible for program&#xD;
      referral. Each weekday morning actively admitted patients at eight study hospitals will be&#xD;
      identified from the electronic health record and Enterprise Data Warehouse and output into&#xD;
      daily eligibility lists based on the study's inclusion/exclusion criteria. Primary analyses&#xD;
      will be conducted using an intent-to-treat approach such that all eligible patients will be&#xD;
      included. Planned enrollment is 4032 patients and STAR program follow-up will be completed 90&#xD;
      days after hospital discharge. Outcomes data will be tracked for 90 days and captured from&#xD;
      routinely collected data from the Atrium Health Enterprise Data Warehouse. Given this&#xD;
      evaluation protocol relies on using evidence-based interventions, only utilizes data&#xD;
      collected as part of routine care, and is minimal risk to patients, the institutional review&#xD;
      board granted the request for waiver of informed consent.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 1, 2020</start_date>
  <completion_date type="Anticipated">April 2024</completion_date>
  <primary_completion_date type="Anticipated">September 2023</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>
    <intervention_model_description>Pragmatic, stepped-wedge cluster randomized controlled trial</intervention_model_description>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>All-cause mortality and hospital readmission rate</measure>
    <time_frame>90 days</time_frame>
    <description>Binary composite endpoint of mortality and hospital readmission assessed 90 days post index hospital discharge</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of days alive and outside the hospital</measure>
    <time_frame>90 days</time_frame>
    <description>Continuous composite endpoint of days alive and outside of the hospital assessed 90 days post index hospital discharge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause mortality rate</measure>
    <time_frame>90 days</time_frame>
    <description>Binary endpoint of all-cause mortality rate assessed 90 days post index hospital discharge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause hospital readmission rate</measure>
    <time_frame>90 days</time_frame>
    <description>Binary endpoint of all-cause hospital readmission rate assessed 90 days post index hospital discharge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of outpatient provider visits</measure>
    <time_frame>90 days</time_frame>
    <description>Number of outpatient provider visits assessed 90 days post index hospital discharge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of emergency department visits</measure>
    <time_frame>90 days</time_frame>
    <description>Number of emergency department visits assessed 90 days post index hospital discharge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cause-specific hospital readmission rate</measure>
    <time_frame>90 days</time_frame>
    <description>Binary endpoint of cause-specific readmission rate for infection, chronic lung disease, heart failure, acute renal failure, and ambulatory care sensitive conditions assessed 90 days post index hospital discharge</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Cost-Effectiveness</measure>
    <time_frame>90 days, 1 year</time_frame>
    <description>A comparison of the STAR and usual care strategies based on the incremental cost-effectiveness ratio (ICER). The ICER is defined as the difference in costs between interventions, divided by the difference in combined mortality and readmission rates</description>
  </other_outcome>
  <other_outcome>
    <measure>Qualitative assessment of the barriers to STAR program implementation</measure>
    <time_frame>Pre-implementation, 8 months, 20 months, 32 months, 36 months (i.e., Post-implementation)</time_frame>
    <description>Open-ended, qualitative assessment guided by the Consolidated Framework for Implementation Research to identify perceived barriers to implementing the STAR program into the peri-discharge setting. Themes will be categorized and reported as percentages of participants.</description>
  </other_outcome>
  <other_outcome>
    <measure>Qualitative assessment of the facilitators to STAR program implementation</measure>
    <time_frame>Pre-implementation, 8 months, 20 months, 32 months, 36 months (i.e., Post-implementation)</time_frame>
    <description>Open-ended, qualitative assessment guided by the Consolidated Framework for Implementation Research to identify perceived facilitators to implementing the STAR program into the peri-discharge setting. Themes will be categorized and reported as percentages of participants.</description>
  </other_outcome>
  <other_outcome>
    <measure>Number of eligible patients reached by STAR program</measure>
    <time_frame>8 months, 20 months, 32 months, 36 months (i.e., Post-implementation)</time_frame>
    <description>Navigator use per eligible patients</description>
  </other_outcome>
  <other_outcome>
    <measure>Number of providers included in STAR program adoption</measure>
    <time_frame>8 months, 20 months, 32 months, 36 months (i.e., Post-implementation)</time_frame>
    <description>Number of providers with patients enrolled</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">4032</enrollment>
  <condition>Sepsis</condition>
  <arm_group>
    <arm_group_label>Sepsis Transition and Recovery (STAR) Program</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Virtual sepsis navigation delivered across the peri-hospital discharge interval</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Usual Care</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Standard of care received through Atrium Health facilities for patients hospitalized with sepsis. Aspects of usual care will be determined by treating clinicians independent of trial assignment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Sepsis Transition and Recovery (STAR) program</intervention_name>
    <description>In the STAR program intervention, a centrally located nurse navigator facilitates the application of four evidence-based core components of post-sepsis care (i.e., review of medications, new impairments, comorbidities, and palliative care) to patients prior to and during the 90 days after hospital discharge. The STAR navigator will provide telephone and EHR-based support within the hospitalization and to patients across all discharge settings with remote monitoring at specified intervals following hospital discharge. Patients will continue to receive STAR directed services for 90 days following their discharge and then will be transitioned back to the next appropriate care location.</description>
    <arm_group_label>Sepsis Transition and Recovery (STAR) Program</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Usual care</intervention_name>
    <description>Hospitals and their patients will not have access to the STAR program. Patients will continue to receive usual care throughout their stay and discharge, consisting of: patient education and follow-up instructions at discharge, which are not specific to sepsis; routine recommendations for follow-up visits with primary care providers; arrangements for home health services or care management follow-up based on each patient's needs but not specifically tailored to the sepsis population; discharge to post-acute setting with no sepsis-specific follow-up. All aspects of usual care will be determined by treating clinicians independent of trial assignment.</description>
    <arm_group_label>Usual Care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. At least 18 years of age upon admission&#xD;
&#xD;
          2. Suspected infection&#xD;
&#xD;
               1. Oral/parenteral antibiotic or bacterial culture order within 24 hours of&#xD;
                  emergency department presentation; and&#xD;
&#xD;
               2. Evidence of systemic inflammatory response (i.e., at least two abnormal of&#xD;
                  temperature; heart rate; respiratory rate; and WBC count or bands)&#xD;
&#xD;
          3. Evidence of organ dysfunction (i.e., at least two points on either Quick&#xD;
             Sepsis-related Organ Failure Assessment or Sepsis-related Organ Failure Assessment&#xD;
             risk tools)&#xD;
&#xD;
          4. Deemed as high risk for 90-day readmission using risk-scoring models&#xD;
&#xD;
          5. Not discharged at the time of patient list generation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with a change in code status (i.e., do not resuscitate, do not intubate)&#xD;
             within 24 hours after infection onset due to presumed limitation of aggressive&#xD;
             treatment&#xD;
&#xD;
          2. Patients who reside &gt; 2.5 hours drive time from the treating hospital&#xD;
&#xD;
          3. Patients actively enrolled in a different care management program at time of admission&#xD;
&#xD;
          4. Patient has been randomized previously.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marc Kowalkowski, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Wake Forest University Health Sciences</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Stephanie P Taylor, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Wake Forest University Health Sciences</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Marc Kowalkowski, PhD</last_name>
    <phone>704-355-9902</phone>
    <email>marc.kowalkowski@atriumhealth.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Stephanie Taylor, MD</last_name>
    <phone>704 355-3819</phone>
    <email>stephanie.p.taylor@atriumhealth.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Atrium Health</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28203</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marc Kowalkowski, PhD</last_name>
      <phone>704-355-9902</phone>
      <email>marc.kowalkowski@atriumhealth.org</email>
    </contact>
    <investigator>
      <last_name>Stephanie P Taylor, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Marc Kowalkowski, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Fleischmann C, Scherag A, Adhikari NK, Hartog CS, Tsaganos T, Schlattmann P, Angus DC, Reinhart K; International Forum of Acute Care Trialists. Assessment of Global Incidence and Mortality of Hospital-treated Sepsis. Current Estimates and Limitations. Am J Respir Crit Care Med. 2016 Feb 1;193(3):259-72. doi: 10.1164/rccm.201504-0781OC.</citation>
    <PMID>26414292</PMID>
  </reference>
  <reference>
    <citation>Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-377. doi: 10.1007/s00134-017-4683-6. Epub 2017 Jan 18.</citation>
    <PMID>28101605</PMID>
  </reference>
  <reference>
    <citation>Kaukonen KM, Bailey M, Suzuki S, Pilcher D, Bellomo R. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012. JAMA. 2014 Apr 2;311(13):1308-16. doi: 10.1001/jama.2014.2637.</citation>
    <PMID>24638143</PMID>
  </reference>
  <reference>
    <citation>Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010 Oct 27;304(16):1787-94. doi: 10.1001/jama.2010.1553.</citation>
    <PMID>20978258</PMID>
  </reference>
  <reference>
    <citation>Borges RC, Carvalho CR, Colombo AS, da Silva Borges MP, Soriano FG. Physical activity, muscle strength, and exercise capacity 3 months after severe sepsis and septic shock. Intensive Care Med. 2015 Aug;41(8):1433-44. doi: 10.1007/s00134-015-3914-y. Epub 2015 Jun 25.</citation>
    <PMID>26109398</PMID>
  </reference>
  <reference>
    <citation>Annane D, Sharshar T. Cognitive decline after sepsis. Lancet Respir Med. 2015 Jan;3(1):61-9. doi: 10.1016/S2213-2600(14)70246-2. Epub 2014 Nov 28.</citation>
    <PMID>25434614</PMID>
  </reference>
  <reference>
    <citation>Prescott HC, Langa KM, Iwashyna TJ. Readmission diagnoses after hospitalization for severe sepsis and other acute medical conditions. JAMA. 2015 Mar 10;313(10):1055-7. doi: 10.1001/jama.2015.1410. No abstract available.</citation>
    <PMID>25756444</PMID>
  </reference>
  <reference>
    <citation>Mayr FB, Talisa VB, Balakumar V, Chang CH, Fine M, Yende S. Proportion and Cost of Unplanned 30-Day Readmissions After Sepsis Compared With Other Medical Conditions. JAMA. 2017 Feb 7;317(5):530-531. doi: 10.1001/jama.2016.20468. No abstract available.</citation>
    <PMID>28114505</PMID>
  </reference>
  <reference>
    <citation>Prescott HC, Angus DC. Enhancing Recovery From Sepsis: A Review. JAMA. 2018 Jan 2;319(1):62-75. doi: 10.1001/jama.2017.17687.</citation>
    <PMID>29297082</PMID>
  </reference>
  <reference>
    <citation>Taylor SP, Chou SH, Sierra MF, Shuman TP, McWilliams AD, Taylor BT, Russo M, Evans SL, Rossman W, Murphy S, Cunningham K, Kowalkowski MA. Association between Adherence to Recommended Care and Outcomes for Adult Survivors of Sepsis. Ann Am Thorac Soc. 2020 Jan;17(1):89-97. doi: 10.1513/AnnalsATS.201907-514OC.</citation>
    <PMID>31644304</PMID>
  </reference>
  <reference>
    <citation>Brownson RC, Allen P, Duggan K, Stamatakis KA, Erwin PC. Fostering more-effective public health by identifying administrative evidence-based practices: a review of the literature. Am J Prev Med. 2012 Sep;43(3):309-19. doi: 10.1016/j.amepre.2012.06.006.</citation>
    <PMID>22898125</PMID>
  </reference>
  <reference>
    <citation>Bodenheimer T. Coordinating care--a perilous journey through the health care system. N Engl J Med. 2008 Mar 6;358(10):1064-71. doi: 10.1056/NEJMhpr0706165. No abstract available.</citation>
    <PMID>18322289</PMID>
  </reference>
  <reference>
    <citation>Coleman EA, Berenson RA. Lost in transition: challenges and opportunities for improving the quality of transitional care. Ann Intern Med. 2004 Oct 5;141(7):533-6. doi: 10.7326/0003-4819-141-7-200410050-00009.</citation>
    <PMID>15466770</PMID>
  </reference>
  <reference>
    <citation>Kim CS, Flanders SA. In the Clinic. Transitions of care. Ann Intern Med. 2013 Mar 5;158(5 Pt 1):ITC3-1. doi: 10.7326/0003-4819-158-5-201303050-01003. No abstract available.</citation>
    <PMID>23460071</PMID>
  </reference>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>July 7, 2020</study_first_submitted>
  <study_first_submitted_qc>July 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 3, 2020</study_first_posted>
  <last_update_submitted>April 21, 2023</last_update_submitted>
  <last_update_submitted_qc>April 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 24, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>evidence based medicine</keyword>
  <keyword>transition care</keyword>
  <keyword>critical care</keyword>
  <keyword>implementation science</keyword>
  <keyword>pragmatic clinical trial</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sepsis</mesh_term>
    <mesh_term>Toxemia</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/NCT04495946
org study id: Pro00036873
secondary id: R01NR018434
nct id: NCT04495946
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to evaluate if implementation of the Sepsis Transition and
      Recovery (STAR) program within a large healthcare system will improve outcomes for high-risk
      patients with suspected sepsis, while concurrently examining contextual factors related to
      STAR program delivery within routine care to generate knowledge of best practices for
      implementation and dissemination of post sepsis transitions of care. To address persistent
      morbidity and mortality for sepsis survivors, Atrium Health developed the Sepsis Treatment
      and Recovery (STAR) program which uses a nurse navigator to deliver a bundle of best-practice
      care elements for the delivery of longitudinal post-sepsis care for up to 90 days. These care
      elements are directed towards the specific challenges and sequelae following a sepsis
      hospitalization and include: 1) identification and treatment of new physical, mental, and
      cognitive deficits; 2) review and adjustment of medications; 3) surveillance of treatable
      conditions that commonly lead to poor outcomes including chronic conditions that may
      de-stabilize during sepsis and recovery; and 4) focus on palliative care when appropriate.
      ENCOMPASS (Engagement and Collaborative Management to Proactively Advance Sepsis
      Survivorship) is an effectiveness-implementation hybrid type I trial, with the evaluation
      designed as a two-arm, pragmatic, stepped-wedge cluster randomized controlled trial conducted
      at eight regional hospitals in which each participating hospital begins in a usual care
      control phase and transitions to the STAR program intervention in a randomly assigned
      sequence. Patients are allocated to receive the treatment condition (i.e., usual care or
      STAR) assigned to their admission hospital at time of enrollment. ENCOMPASS will test the
      hypothesis that patients who receive care through the STAR program will have reduced
      mortality and hospital readmission assessed 90 days post index hospital discharge compared to
      patients who receive usual care.
BACKGROUND

      Sepsis is a common and life-threatening condition defined by organ dysfunction due to a
      dysregulated response to infection (Fleischmann, 2016). Aggressive early sepsis
      identification and treatment initiatives have decreased hospital mortality for patients with
      sepsis (Rhodes, 2017; Kaukonen, 2014). However, sepsis survivors continue to face challenges
      after the acute illness episode, experiencing new functional, cognitive, and psychological
      deficits, and high rates of hospital readmission and mortality in the 90-days after hospital
      discharge (Iwashyna, 2010; Borges, 2015; Annane, 2015; Prescott, 2015; Mayr, 2017). To
      address persistent morbidity and mortality for sepsis survivors, Atrium Health developed the
      Sepsis Treatment and Recovery (STAR) program which uses a nurse navigator to deliver a bundle
      of best-practice care elements for the delivery of longitudinal post-sepsis care for up to 90
      days. These care elements are directed towards the specific challenges and sequelae following
      a sepsis hospitalization and include: 1) identification and treatment of new physical,
      mental, and cognitive deficits; 2) review and adjustment of medications; 3) surveillance of
      treatable conditions that commonly lead to poor outcomes including chronic conditions that
      may destabilize during sepsis and recovery; and 4) focus on palliative care when appropriate
      (Prescott, 2018) These care elements have good face-validity and have shown to be associated
      with improved outcomes for sepsis survivors in observational data (Taylor, 2020). However,
      they are not widely applied in real-world settings for this vulnerable population, likely
      hindered by a gap in understanding key contextual factors underlying how to best integrate
      this bundle of care elements into the complex and fragmented post-discharge setting
      (Brownson, 2012; Bodenheimer, 2008; Coleman, 2004; Kim, 2013)

      RATIONALE

      In randomized controlled trials (RCTs), successfully implemented care transition programs
      using nurse navigators have been shown to reduce hospital readmission and costs. To better
      enhance transitions of care for the highest risk, complex patients with suspected sepsis, the
      investigators propose extending this evidence using a nurse-facilitated care transition
      program for patients in the post-sepsis transition period to improve the implementation of
      recommended care practices and bridge care gaps. This approach, called the Sepsis Transition
      and Recovery (STAR) program, is the next step in the progression of the investigator team's
      work on improving discharge transitions and sepsis processes of care. A key aspect of this
      initiative includes the ability to identify sepsis survivors at the greatest risk for poor
      outcomes. For example, one-quarter of sepsis survivors account for three-quarters of hospital
      readmission and costs, indicating that identifying high-risk sepsis patients for targeted
      facilitation of best-practice care could efficiently impact quality and cost.

      The STAR program uses near real-time risk modeling to identify high-risk patients and a
      centrally located nurse, virtually connected to participating hospitals, to coordinate the
      application of evidence-based recommendations for post-sepsis care, overcome barriers to
      recommended care, and bridge gaps in service that can serve as points of failure for complex
      patients. During hospitalization, high-risk patients enter into a transition pathway
      integrated within Atrium Health Hospital Medicine's Transition Services program and includes
      the following core components: i) Introduction to STAR process prior to discharge (confirm
      provider consults e.g., PT, ID, palliative); ii) Disease-specific education and discharge
      "playbook"; iii) Virtual hospital follow-up evaluation within 48 hours including medication
      reconciliation; iv) Second, post-acute virtual follow-up within 72-96 hours (symptom
      monitoring, confirm provider follow-up); v) Weekly contact with STAR team; vi) Referral to
      provider follow-up (e.g., primary care provider, transition clinic) as appropriate; vii)
      Coordinated transition to the next appropriate care location after 90 days from time of
      discharge. The STAR navigator also meets weekly with the Medical Director of the Atrium
      Health Transition Services program who provides additional clinical oversight of ongoing
      cases.

      The ENCOMPASS (Engagement and Collaborative Management to Proactively Advance Sepsis
      Survivorship) evaluation will examine if implementation of the STAR program within a large
      healthcare system will improve outcomes for high-risk sepsis patients. This cluster
      randomized program evaluation is designed to be a seamless part of routine care in a
      real-world setting to generate knowledge of best practices for implementation and
      dissemination of post-sepsis transitions of care.

      INVESTIGATIONAL PLAN

      Overall Study Design ENCOMPASS is an effectiveness-implementation hybrid type I trial. The
      evaluation component is designed as a two-arm, pragmatic, stepped-wedge cluster randomized
      controlled trial conducted at eight regional hospitals in which each participating hospital
      begins in a usual care control phase and transitions to the STAR program intervention in a
      randomly assigned sequence, with one of eight hospitals assigned to transition at each
      four-month interval (i.e., step). During the time that a hospital is allocated to usual care,
      all eligible patients will receive usual care. Once a hospital has been allocated to the STAR
      arm, all eligible patients will receive STAR during their index hospitalization and extending
      through 90 days from discharge or date of death. The ENCOMPASS trial will compare the
      effectiveness of the Sepsis Transition And Recovery (STAR) program versus usual care on
      post-sepsis care and patient outcomes. The STAR program is informed by existing evidence and
      designed using the Chronic Care Model to increase best-practice adherence and care
      coordination, resulting in improved transitions between hospitals and post-acute care during
      sepsis recovery.

      ENCOMPASS will test the STAR program intervention within the course of providing usual care
      among a large and diverse population of post-sepsis patients admitted to eight hospitals
      within Atrium Health, one of the largest, vertically integrated health systems in the US. The
      eight acute care hospitals participating in this study use the same EHR, which connects
      across all points of care, including outpatient practices, urgent care locations, emergency
      departments and hospitals. Consistent with the pragmatic study design concept, eligibility
      criteria are broad, the sample size is large and diverse, and study procedures are embedded
      into the context of routine care. To be objective in patient selection and allow for program
      evaluation, a data driven approach will be used to identify patients as eligible for program
      referral. Each weekday morning actively admitted patients at eight study hospitals will be
      identified from the electronic health record and Enterprise Data Warehouse and output into
      daily eligibility lists based on the study's inclusion/exclusion criteria. Primary analyses
      will be conducted using an intent-to-treat approach such that all eligible patients will be
      included. Planned enrollment is 4032 patients and STAR program follow-up will be completed 90
      days after hospital discharge. Outcomes data will be tracked for 90 days and captured from
      routinely collected data from the Atrium Health Enterprise Data Warehouse. Given this
      evaluation protocol relies on using evidence-based interventions, only utilizes data
      collected as part of routine care, and is minimal risk to patients, the institutional review
      board granted the request for waiver of informed consent.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Pragmatic, stepped-wedge cluster randomized controlled trial
primary purpose: Health Services Research
masking: Single (Outcomes Assessor)
measure: All-cause mortality and hospital readmission rate
time frame: 90 days
description: Binary composite endpoint of mortality and hospital readmission assessed 90 days post index hospital discharge
measure: Number of days alive and outside the hospital
time frame: 90 days
description: Continuous composite endpoint of days alive and outside of the hospital assessed 90 days post index hospital discharge
measure: All-cause mortality rate
time frame: 90 days
description: Binary endpoint of all-cause mortality rate assessed 90 days post index hospital discharge
measure: All-cause hospital readmission rate
time frame: 90 days
description: Binary endpoint of all-cause hospital readmission rate assessed 90 days post index hospital discharge
measure: Number of outpatient provider visits
time frame: 90 days
description: Number of outpatient provider visits assessed 90 days post index hospital discharge
measure: Number of emergency department visits
time frame: 90 days
description: Number of emergency department visits assessed 90 days post index hospital discharge
measure: Cause-specific hospital readmission rate
time frame: 90 days
description: Binary endpoint of cause-specific readmission rate for infection, chronic lung disease, heart failure, acute renal failure, and ambulatory care sensitive conditions assessed 90 days post index hospital discharge
measure: Cost-Effectiveness
time frame: 90 days, 1 year
description: A comparison of the STAR and usual care strategies based on the incremental cost-effectiveness ratio (ICER). The ICER is defined as the difference in costs between interventions, divided by the difference in combined mortality and readmission rates
measure: Qualitative assessment of the barriers to STAR program implementation
time frame: Pre-implementation, 8 months, 20 months, 32 months, 36 months (i.e., Post-implementation)
description: Open-ended, qualitative assessment guided by the Consolidated Framework for Implementation Research to identify perceived barriers to implementing the STAR program into the peri-discharge setting. Themes will be categorized and reported as percentages of participants.
measure: Qualitative assessment of the facilitators to STAR program implementation
time frame: Pre-implementation, 8 months, 20 months, 32 months, 36 months (i.e., Post-implementation)
description: Open-ended, qualitative assessment guided by the Consolidated Framework for Implementation Research to identify perceived facilitators to implementing the STAR program into the peri-discharge setting. Themes will be categorized and reported as percentages of participants.
measure: Number of eligible patients reached by STAR program
time frame: 8 months, 20 months, 32 months, 36 months (i.e., Post-implementation)
description: Navigator use per eligible patients
measure: Number of providers included in STAR program adoption
time frame: 8 months, 20 months, 32 months, 36 months (i.e., Post-implementation)
description: Number of providers with patients enrolled
arm group label: Sepsis Transition and Recovery (STAR) Program
arm group type: Experimental
description: Virtual sepsis navigation delivered across the peri-hospital discharge interval
arm group label: Usual Care
arm group type: Active Comparator
description: Standard of care received through Atrium Health facilities for patients hospitalized with sepsis. Aspects of usual care will be determined by treating clinicians independent of trial assignment.
intervention type: Behavioral
intervention name: Sepsis Transition and Recovery (STAR) program
description: In the STAR program intervention, a centrally located nurse navigator facilitates the application of four evidence-based core components of post-sepsis care (i.e., review of medications, new impairments, comorbidities, and palliative care) to patients prior to and during the 90 days after hospital discharge. The STAR navigator will provide telephone and EHR-based support within the hospitalization and to patients across all discharge settings with remote monitoring at specified intervals following hospital discharge. Patients will continue to receive STAR directed services for 90 days following their discharge and then will be transitioned back to the next appropriate care location.
arm group label: Sepsis Transition and Recovery (STAR) Program
intervention type: Behavioral
intervention name: Usual care
description: Hospitals and their patients will not have access to the STAR program. Patients will continue to receive usual care throughout their stay and discharge, consisting of: patient education and follow-up instructions at discharge, which are not specific to sepsis; routine recommendations for follow-up visits with primary care providers; arrangements for home health services or care management follow-up based on each patient's needs but not specifically tailored to the sepsis population; discharge to post-acute setting with no sepsis-specific follow-up. All aspects of usual care will be determined by treating clinicians independent of trial assignment.
arm group label: Usual Care
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Marc Kowalkowski, PhD
role: Principal Investigator
affiliation: Wake Forest University Health Sciences
last name: Stephanie P Taylor, MD
role: Principal Investigator
affiliation: Wake Forest University Health Sciences
last name: Marc Kowalkowski, PhD
phone: 704-355-9902
email: marc.kowalkowski@atriumhealth.org
last name: Stephanie Taylor, MD
phone: 704 355-3819
email: stephanie.p.taylor@atriumhealth.org
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: United States
citation: Fleischmann C, Scherag A, Adhikari NK, Hartog CS, Tsaganos T, Schlattmann P, Angus DC, Reinhart K; International Forum of Acute Care Trialists. Assessment of Global Incidence and Mortality of Hospital-treated Sepsis. Current Estimates and Limitations. Am J Respir Crit Care Med. 2016 Feb 1;193(3):259-72. doi: 10.1164/rccm.201504-0781OC.
PMID: 26414292
citation: Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-377. doi: 10.1007/s00134-017-4683-6. Epub 2017 Jan 18.
PMID: 28101605
citation: Kaukonen KM, Bailey M, Suzuki S, Pilcher D, Bellomo R. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012. JAMA. 2014 Apr 2;311(13):1308-16. doi: 10.1001/jama.2014.2637.
PMID: 24638143
citation: Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010 Oct 27;304(16):1787-94. doi: 10.1001/jama.2010.1553.
PMID: 20978258
citation: Borges RC, Carvalho CR, Colombo AS, da Silva Borges MP, Soriano FG. Physical activity, muscle strength, and exercise capacity 3 months after severe sepsis and septic shock. Intensive Care Med. 2015 Aug;41(8):1433-44. doi: 10.1007/s00134-015-3914-y. Epub 2015 Jun 25.
PMID: 26109398
citation: Annane D, Sharshar T. Cognitive decline after sepsis. Lancet Respir Med. 2015 Jan;3(1):61-9. doi: 10.1016/S2213-2600(14)70246-2. Epub 2014 Nov 28.
PMID: 25434614
citation: Prescott HC, Langa KM, Iwashyna TJ. Readmission diagnoses after hospitalization for severe sepsis and other acute medical conditions. JAMA. 2015 Mar 10;313(10):1055-7. doi: 10.1001/jama.2015.1410. No abstract available.
PMID: 25756444
citation: Mayr FB, Talisa VB, Balakumar V, Chang CH, Fine M, Yende S. Proportion and Cost of Unplanned 30-Day Readmissions After Sepsis Compared With Other Medical Conditions. JAMA. 2017 Feb 7;317(5):530-531. doi: 10.1001/jama.2016.20468. No abstract available.
PMID: 28114505
citation: Prescott HC, Angus DC. Enhancing Recovery From Sepsis: A Review. JAMA. 2018 Jan 2;319(1):62-75. doi: 10.1001/jama.2017.17687.
PMID: 29297082
citation: Taylor SP, Chou SH, Sierra MF, Shuman TP, McWilliams AD, Taylor BT, Russo M, Evans SL, Rossman W, Murphy S, Cunningham K, Kowalkowski MA. Association between Adherence to Recommended Care and Outcomes for Adult Survivors of Sepsis. Ann Am Thorac Soc. 2020 Jan;17(1):89-97. doi: 10.1513/AnnalsATS.201907-514OC.
PMID: 31644304
citation: Brownson RC, Allen P, Duggan K, Stamatakis KA, Erwin PC. Fostering more-effective public health by identifying administrative evidence-based practices: a review of the literature. Am J Prev Med. 2012 Sep;43(3):309-19. doi: 10.1016/j.amepre.2012.06.006.
PMID: 22898125
citation: Bodenheimer T. Coordinating care--a perilous journey through the health care system. N Engl J Med. 2008 Mar 6;358(10):1064-71. doi: 10.1056/NEJMhpr0706165. No abstract available.
PMID: 18322289
citation: Coleman EA, Berenson RA. Lost in transition: challenges and opportunities for improving the quality of transitional care. Ann Intern Med. 2004 Oct 5;141(7):533-6. doi: 10.7326/0003-4819-141-7-200410050-00009.
PMID: 15466770
citation: Kim CS, Flanders SA. In the Clinic. Transitions of care. Ann Intern Med. 2013 Mar 5;158(5 Pt 1):ITC3-1. doi: 10.7326/0003-4819-158-5-201303050-01003. No abstract available.
PMID: 23460071
responsible party type: Sponsor
mesh term: Sepsis
mesh term: Toxemia
sharing ipd: No