<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/NCT01663701</url>
  </required_header>
  <id_info>
    <org_study_id>SSSP-2</org_study_id>
    <secondary_id>R24TW007988</secondary_id>
    <nct_id>NCT01663701</nct_id>
  </id_info>
  <brief_title>Simplified Severe Sepsis Protocol-2 (SSSP-2) in Zambia</brief_title>
  <acronym>SSSP-2</acronym>
  <official_title>Simplified Severe Sepsis Protocol-2 (SSSP-2): A Randomized Controlled Trial of a Bundled Intervention for Severe Sepsis at the University Teaching Hospital in Zambia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Fogarty International Center of the National Institute of Health</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Vanderbilt University Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is a randomized control trial assessing the impact of a simple evidence-based&#xD;
      protocol for the treatment severe sepsis with hypotension in Zambia. This is a follow-up&#xD;
      study to the Simplified Severe Sepsis Protocol (SSSP) study. The intervention protocol&#xD;
      consists of a scheduled fluid regimen, early blood culture and antibiotics, and dopamine and&#xD;
      blood transfusion when necessary. It is hypothesized that the protocol will significantly&#xD;
      decrease in-hospital mortality in patients with severe sepsis and hypotension.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In recent years, evidence-based protocols of bundled therapies have improved survival of&#xD;
      severe sepsis in developed countries. In sub-Saharan Africa, simple therapies such as IV&#xD;
      fluids and early antibiotics are frequently under-utilized. Studies of fluid interventions in&#xD;
      the region, however, have demonstrated conflicting results. Outcomes in septic patients may&#xD;
      be further affected by delays in the diagnosis of tuberculosis-associated severe sepsis.&#xD;
&#xD;
      The aims of this study are (1) To assess the impact on survival of a simple evidence-based&#xD;
      protocol for severe sepsis with hypotensionor septic shock, (2) To evaluate the cost of&#xD;
      implementation for a simplified severe sepsis protocol, (3) To develop a clinical diagnostic&#xD;
      score for identifying tuberculosis in HIV positive patients with severe sepsis, and (4) To&#xD;
      assess the performance of the Xpert TB/RIF rapid PCR system and urine lipoarabinomannan assay&#xD;
      for diagnosing tuberculosis in HIV positive patients with severe sepsis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2012</start_date>
  <completion_date type="Actual">January 2014</completion_date>
  <primary_completion_date type="Actual">November 2013</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>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>In-hospital all cause mortality</measure>
    <time_frame>During hospitalization, expected average 14 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>28-day all-cause mortality</measure>
    <time_frame>28-day</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>In-hospital all cause mortality adjusted for illness severity</measure>
    <time_frame>During hospitalization, expected average 14 days</time_frame>
    <description>Adjusted for SAPS3 score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>28-day all cause mortality adjusted for baseline illness severity</measure>
    <time_frame>28-day</time_frame>
    <description>Adjusted for SAPS3 score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative adverse events</measure>
    <time_frame>During hospitalization, expected average 14 days</time_frame>
    <description>A composite outcome consisting of dopamine extravasation, dopamine-associated tissue ischemia or necrosis, iatrogenic pulmonary oedema, and transfusion-related adverse events.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment cost per patient</measure>
    <time_frame>During hospitalization, expected average 14 days</time_frame>
    <description>A budget impact analysis will determine the cost of treatment per patient using a mix of direct measurements and micro-cost observation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antibiotic changed due to culture results</measure>
    <time_frame>During hospitalization, expected average 14 days</time_frame>
    <description>The proportion of patients whose antibiotic regimen was changed due to information obtained from blood culture results.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">212</enrollment>
  <condition>Sepsis</condition>
  <condition>Severe Sepsis</condition>
  <condition>Tuberculosis</condition>
  <arm_group>
    <arm_group_label>Usual care</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients are managed according to admitting doctors' orders. Blood cultures are drawn in all patients. Antibiotics are specified by the admitting doctors.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Simplified Severe Sepsis Protocol</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This protocol consists of an early aggressive fluid strategy, early blood cultures and antibiotics, and, when appropriate, blood transfusion and titratable dopamine. Monitoring is based on physical exam findings. Antibiotics are specified by the admitting doctors.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Simplified severe sepsis protocol</intervention_name>
    <description>This protocol consists of an early aggressive fluid strategy, and, when appropriate, blood transfusion and titratable dopamine. Monitoring is based on physical exam findings.</description>
    <arm_group_label>Simplified Severe Sepsis Protocol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Usual care</intervention_name>
    <description>Patients are managed according to admitting doctors' orders</description>
    <arm_group_label>Usual care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  infection suspected by the treating physician&#xD;
&#xD;
          -  2 or more of the following SIRS criteria:&#xD;
&#xD;
          -  - Heart rate &gt;90/min&#xD;
&#xD;
          -  Respiratory rate &gt;20/min&#xD;
&#xD;
          -  - Temperature ≥ 38° C or &lt; 36° C&#xD;
&#xD;
          -  White blood count &gt; 12,000 or &lt; 4,000/µL&#xD;
&#xD;
          -  1 of the following:&#xD;
&#xD;
          -  Systolic blood pressure (SBP) ≤ 90 mm Hg&#xD;
&#xD;
          -  Mean arterial blood pressure (MAP) ≤ 65 mm Hg&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Gastrointestinal bleed in the absence of fever&#xD;
&#xD;
          -  Need for immediate surgery&#xD;
&#xD;
          -  Respiratory rate greater than 40/min with oxygen saturation less than 90%&#xD;
&#xD;
          -  Suspected congestive heart failure exacerbation&#xD;
&#xD;
          -  End-stage renal disease&#xD;
&#xD;
          -  Raised jugular venous pressure (JVP) at baseline&#xD;
&#xD;
          -  Currently incarcerated&#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>Benjamin L Andrews, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vanderbilt University and University of Zambia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Teaching Hospital</name>
      <address>
        <city>Lusaka</city>
        <country>Zambia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Zambia</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>August 8, 2012</study_first_submitted>
  <study_first_submitted_qc>August 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2012</study_first_posted>
  <last_update_submitted>September 23, 2021</last_update_submitted>
  <last_update_submitted_qc>September 23, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 30, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Sepsis</keyword>
  <keyword>Severe sepsis</keyword>
  <keyword>Tuberculosis</keyword>
  <keyword>Bundle</keyword>
  <keyword>Zambia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sepsis</mesh_term>
    <mesh_term>Toxemia</mesh_term>
    <mesh_term>Tuberculosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Requests for data sharing should be directed to PI. PI will then confer with Zambian co-PI to confirm that data sharing is allowable by Zambian law.</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/NCT01663701
org study id: SSSP-2
secondary id: R24TW007988
nct id: NCT01663701
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
This study is a randomized control trial assessing the impact of a simple evidence-based
      protocol for the treatment severe sepsis with hypotension in Zambia. This is a follow-up
      study to the Simplified Severe Sepsis Protocol (SSSP) study. The intervention protocol
      consists of a scheduled fluid regimen, early blood culture and antibiotics, and dopamine and
      blood transfusion when necessary. It is hypothesized that the protocol will significantly
      decrease in-hospital mortality in patients with severe sepsis and hypotension.
In recent years, evidence-based protocols of bundled therapies have improved survival of
      severe sepsis in developed countries. In sub-Saharan Africa, simple therapies such as IV
      fluids and early antibiotics are frequently under-utilized. Studies of fluid interventions in
      the region, however, have demonstrated conflicting results. Outcomes in septic patients may
      be further affected by delays in the diagnosis of tuberculosis-associated severe sepsis.

      The aims of this study are (1) To assess the impact on survival of a simple evidence-based
      protocol for severe sepsis with hypotensionor septic shock, (2) To evaluate the cost of
      implementation for a simplified severe sepsis protocol, (3) To develop a clinical diagnostic
      score for identifying tuberculosis in HIV positive patients with severe sepsis, and (4) To
      assess the performance of the Xpert TB/RIF rapid PCR system and urine lipoarabinomannan assay
      for diagnosing tuberculosis in HIV positive patients with severe sepsis.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: In-hospital all cause mortality
time frame: During hospitalization, expected average 14 days
measure: 28-day all-cause mortality
time frame: 28-day
measure: In-hospital all cause mortality adjusted for illness severity
time frame: During hospitalization, expected average 14 days
description: Adjusted for SAPS3 score
measure: 28-day all cause mortality adjusted for baseline illness severity
time frame: 28-day
description: Adjusted for SAPS3 score
measure: Cumulative adverse events
time frame: During hospitalization, expected average 14 days
description: A composite outcome consisting of dopamine extravasation, dopamine-associated tissue ischemia or necrosis, iatrogenic pulmonary oedema, and transfusion-related adverse events.
measure: Treatment cost per patient
time frame: During hospitalization, expected average 14 days
description: A budget impact analysis will determine the cost of treatment per patient using a mix of direct measurements and micro-cost observation.
measure: Antibiotic changed due to culture results
time frame: During hospitalization, expected average 14 days
description: The proportion of patients whose antibiotic regimen was changed due to information obtained from blood culture results.
arm group label: Usual care
arm group type: Active Comparator
description: Patients are managed according to admitting doctors' orders. Blood cultures are drawn in all patients. Antibiotics are specified by the admitting doctors.
arm group label: Simplified Severe Sepsis Protocol
arm group type: Experimental
description: This protocol consists of an early aggressive fluid strategy, early blood cultures and antibiotics, and, when appropriate, blood transfusion and titratable dopamine. Monitoring is based on physical exam findings. Antibiotics are specified by the admitting doctors.
intervention type: Other
intervention name: Simplified severe sepsis protocol
description: This protocol consists of an early aggressive fluid strategy, and, when appropriate, blood transfusion and titratable dopamine. Monitoring is based on physical exam findings.
arm group label: Simplified Severe Sepsis Protocol
intervention type: Other
intervention name: Usual care
description: Patients are managed according to admitting doctors' orders
arm group label: Usual care
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Benjamin L Andrews, MD
role: Principal Investigator
affiliation: Vanderbilt University and University of Zambia
facility: 
country: Zambia
responsible party type: Sponsor
mesh term: Sepsis
mesh term: Toxemia
mesh term: Tuberculosis
sharing ipd: Yes
ipd description: Requests for data sharing should be directed to PI. PI will then confer with Zambian co-PI to confirm that data sharing is allowable by Zambian law.