<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/NCT02225769</url>
  </required_header>
  <id_info>
    <org_study_id>IZ01Z0_146896</org_study_id>
    <nct_id>NCT02225769</nct_id>
  </id_info>
  <brief_title>Electronic Algorithms Based on Host Biomarkers to Manage Febrile Children</brief_title>
  <acronym>e-POCT</acronym>
  <official_title>Electronic Algorithms Based on Host Biomarkers Point of Care Tests to Decide on Admission and Antibiotic Prescription in Tanzanian Febrile Children</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Swiss Tropical &amp; Public Health Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Swiss National Science Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Swiss Tropical &amp; Public Health Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Health professionals in developing countries have limited ability to identify children at&#xD;
      risk of dying and those in need of antibiotics. The main reasons are limited clinical skills&#xD;
      and time, unavailability of diagnostic tests (laboratory or x-ray) and non-adherence to&#xD;
      practice guidelines. Child mortality is therefore higher than it should be. Etiological&#xD;
      diagnostic tests (detecting microorganisms) may not always help since the distinction between&#xD;
      infection and disease and between mild or severe disease is not straightforward.&#xD;
      Overprescription of antibiotics is therefore widespread and leads to the development of drug&#xD;
      resistance. To address these challenges, decision charts for the management of febrile&#xD;
      illness will be developed and include i) few clinical parameters simple to assess, and ii)&#xD;
      POCTs results based on specific host markers that can discriminate between mild and severe&#xD;
      disease, pneumonia and upper respiratory tract infections, and unspecific fevers of bacterial&#xD;
      and of viral origin. This algorithm combining clinical and bedside laboratory tests will be&#xD;
      built on an electronic support (android tablet). The first objective of the study is to&#xD;
      assess the safety of new electronic decision trees that integrate simple clinical assessment&#xD;
      and POCTs results (oxygen saturation and a combination of specific biomarkers of&#xD;
      inflammation) as a triage tool to decide on admitting febrile children; the second objective&#xD;
      is to assess the usefulness and safety of new electronic decision trees that integrate simple&#xD;
      clinical assessment and POCT results (a combination of specific biomarkers of inflammation)&#xD;
      as decision-making tool to prescribe antibiotics to non-severe febrile children. The&#xD;
      development of such a tool will decrease mortality due to delayed admission, At the same&#xD;
      time, it will decrease irrational use of antibiotics, and hence drug pressure and emergence&#xD;
      of drug resistance, which represents one of the most important public health threat our world&#xD;
      is facing today. This project has the potential of huge applicability since it is&#xD;
      specifically designed for end-users with limited medical skills and low resources, as it is&#xD;
      the case in most areas of developing countries.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>December 2014</start_date>
  <completion_date type="Actual">February 2016</completion_date>
  <primary_completion_date type="Actual">February 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of clinical failure by day 7 compared among the 3 study arms.</measure>
    <time_frame>10 months</time_frame>
    <description>This outcome measure is used to compare the clinical outcome of febrile children 2-59 months of age managed using e-POCT (intervention arm), ALMANACH (reference control arm) and routine practice (routine control arm).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportions of secondary hospitalization and death by day 30 compared among the 3 study arms.</measure>
    <time_frame>10 months</time_frame>
    <description>This outcome measure is also used to compare the clinical outcome of febrile children 2-59 months of age managed using e-POCT (intervention arm), ALMANACH (reference control arm) and routine practice (routine control arm). This type of event is however too rare to be used as primary endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportions of children prescribed an antibiotic and/or antimalarial treatment at day 0 and by day 7 compared among the 3 study arms.</measure>
    <time_frame>10 months</time_frame>
    <description>This outcome is used to compare the rational use of antimicrobials in treating febrile children using e-POCT, ALMANACH and routine care.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportions of children with hypoxemia, stratified by diagnostic classification (e-POCT arm)</measure>
    <time_frame>10 months</time_frame>
    <description>The aim is to measure the proportion of febrile children with hypoxemia, stratified by diagnostic classification (e-POCT arm only).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of primarily admitted children compared among the 3 study arms.</measure>
    <time_frame>10 months</time_frame>
    <description>The objective is to compare the performance of e-POCT, ALMANACH and routine care in identifying children at risk for life-threatening infection among febrile children.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Diagnostic performance of combinations of host biomarkers in identifying children at risk for life-threatening infections and for clinical failure among children presenting with fever (e-POCT and ALMANACH arms).</measure>
    <time_frame>22 months</time_frame>
    <description>The objective is to explore the performance of combinations of host biomarkers in identifying children in need for antibiotic treatment, by type of infection (ALMANACH arm).</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">3192</enrollment>
  <condition>Acute Febrile Illness</condition>
  <arm_group>
    <arm_group_label>e-POCT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Febrile children managed using the e-POCT tool. The e-POCT tool is an electronic algorithm that integrates key clinical elements with the results of malaria and host biomarkers point-of-care test results (including oximetry).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ALMANACH</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Febrile children managed using the ALMANACH algorithm. ALMANACH is an improved Integrated Management of childhood Illness (IMCI) algorithm based on mobile phones and tablets that has already been assessed for safety and efficacy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Routine practice</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Febrile children managed according to routine care such as provided by routine health facility health workers.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Management of febrile children using e-POCT</intervention_name>
    <description>Use of the e-POCT tool by study clinicians for the clinical management of febrile episodes. The e-POCT tool is an electronic algorithm that integrates key clinical elements with the results of malaria and host biomarkers point-of-care test results (including oximetry).</description>
    <arm_group_label>e-POCT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Management of febrile children using ALMANACH</intervention_name>
    <description>Management of febrile children by study clinicians using ALMANACH. ALMANACH is an improved IMCI algorithm on mobile phone or tablet</description>
    <arm_group_label>ALMANACH</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥2 months and &lt;60 months of age&#xD;
&#xD;
          -  Written informed consent from the child's parent or caregiver&#xD;
&#xD;
          -  Axillary temperature ≥37.5°C and/or tympanic temperature ≥38.0°C&#xD;
&#xD;
          -  History of fever for ≤7 days&#xD;
&#xD;
          -  First consultation for the current illness&#xD;
&#xD;
          -  Live in the catchment area of the health facility&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age 60 months or greater&#xD;
&#xD;
          -  Age less than 2 months&#xD;
&#xD;
          -  Weight less than 2.5kg&#xD;
&#xD;
          -  Chief health problem is an injury, trauma or acute poisoning&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Months</minimum_age>
    <maximum_age>59 Months</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Valérie D'Acremont, MD, PhD, MiH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Swiss Tropical &amp; Public Health Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rangi tatu, Magomeni and Tandale health centers</name>
      <address>
        <city>Dar es Salaam</city>
        <country>Tanzania</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Tanzania</country>
  </location_countries>
  <verification_date>October 2016</verification_date>
  <study_first_submitted>August 22, 2014</study_first_submitted>
  <study_first_submitted_qc>August 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 26, 2014</study_first_posted>
  <last_update_submitted>October 11, 2016</last_update_submitted>
  <last_update_submitted_qc>October 11, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 12, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Swiss Tropical &amp; Public Health Institute</investigator_affiliation>
    <investigator_full_name>Valérie D'Acremont</investigator_full_name>
    <investigator_title>Group leader</investigator_title>
  </responsible_party>
  <keyword>fever</keyword>
  <keyword>point-of-care tests</keyword>
  <keyword>clinical algorithms</keyword>
  <keyword>electronic support</keyword>
  <keyword>host biomarkers</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperthermia</mesh_term>
    <mesh_term>Fever</mesh_term>
  </condition_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/NCT02225769
org study id: IZ01Z0_146896
nct id: NCT02225769
lead sponsor: 
collaborator: 
has dmc: Yes
Health professionals in developing countries have limited ability to identify children at
      risk of dying and those in need of antibiotics. The main reasons are limited clinical skills
      and time, unavailability of diagnostic tests (laboratory or x-ray) and non-adherence to
      practice guidelines. Child mortality is therefore higher than it should be. Etiological
      diagnostic tests (detecting microorganisms) may not always help since the distinction between
      infection and disease and between mild or severe disease is not straightforward.
      Overprescription of antibiotics is therefore widespread and leads to the development of drug
      resistance. To address these challenges, decision charts for the management of febrile
      illness will be developed and include i) few clinical parameters simple to assess, and ii)
      POCTs results based on specific host markers that can discriminate between mild and severe
      disease, pneumonia and upper respiratory tract infections, and unspecific fevers of bacterial
      and of viral origin. This algorithm combining clinical and bedside laboratory tests will be
      built on an electronic support (android tablet). The first objective of the study is to
      assess the safety of new electronic decision trees that integrate simple clinical assessment
      and POCTs results (oxygen saturation and a combination of specific biomarkers of
      inflammation) as a triage tool to decide on admitting febrile children; the second objective
      is to assess the usefulness and safety of new electronic decision trees that integrate simple
      clinical assessment and POCT results (a combination of specific biomarkers of inflammation)
      as decision-making tool to prescribe antibiotics to non-severe febrile children. The
      development of such a tool will decrease mortality due to delayed admission, At the same
      time, it will decrease irrational use of antibiotics, and hence drug pressure and emergence
      of drug resistance, which represents one of the most important public health threat our world
      is facing today. This project has the potential of huge applicability since it is
      specifically designed for end-users with limited medical skills and low resources, as it is
      the case in most areas of developing countries.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Proportion of clinical failure by day 7 compared among the 3 study arms.
time frame: 10 months
description: This outcome measure is used to compare the clinical outcome of febrile children 2-59 months of age managed using e-POCT (intervention arm), ALMANACH (reference control arm) and routine practice (routine control arm).
measure: Proportions of secondary hospitalization and death by day 30 compared among the 3 study arms.
time frame: 10 months
description: This outcome measure is also used to compare the clinical outcome of febrile children 2-59 months of age managed using e-POCT (intervention arm), ALMANACH (reference control arm) and routine practice (routine control arm). This type of event is however too rare to be used as primary endpoint.
measure: Proportions of children prescribed an antibiotic and/or antimalarial treatment at day 0 and by day 7 compared among the 3 study arms.
time frame: 10 months
description: This outcome is used to compare the rational use of antimicrobials in treating febrile children using e-POCT, ALMANACH and routine care.
measure: Proportions of children with hypoxemia, stratified by diagnostic classification (e-POCT arm)
time frame: 10 months
description: The aim is to measure the proportion of febrile children with hypoxemia, stratified by diagnostic classification (e-POCT arm only).
measure: Proportion of primarily admitted children compared among the 3 study arms.
time frame: 10 months
description: The objective is to compare the performance of e-POCT, ALMANACH and routine care in identifying children at risk for life-threatening infection among febrile children.
measure: Diagnostic performance of combinations of host biomarkers in identifying children at risk for life-threatening infections and for clinical failure among children presenting with fever (e-POCT and ALMANACH arms).
time frame: 22 months
description: The objective is to explore the performance of combinations of host biomarkers in identifying children in need for antibiotic treatment, by type of infection (ALMANACH arm).
arm group label: e-POCT
arm group type: Experimental
description: Febrile children managed using the e-POCT tool. The e-POCT tool is an electronic algorithm that integrates key clinical elements with the results of malaria and host biomarkers point-of-care test results (including oximetry).
arm group label: ALMANACH
arm group type: Active Comparator
description: Febrile children managed using the ALMANACH algorithm. ALMANACH is an improved Integrated Management of childhood Illness (IMCI) algorithm based on mobile phones and tablets that has already been assessed for safety and efficacy.
arm group label: Routine practice
arm group type: No Intervention
description: Febrile children managed according to routine care such as provided by routine health facility health workers.
intervention type: Other
intervention name: Management of febrile children using e-POCT
description: Use of the e-POCT tool by study clinicians for the clinical management of febrile episodes. The e-POCT tool is an electronic algorithm that integrates key clinical elements with the results of malaria and host biomarkers point-of-care test results (including oximetry).
arm group label: e-POCT
intervention type: Other
intervention name: Management of febrile children using ALMANACH
description: Management of febrile children by study clinicians using ALMANACH. ALMANACH is an improved IMCI algorithm on mobile phone or tablet
arm group label: ALMANACH
criteria: 
gender: All
minimum age: 2 Months
maximum age: 59 Months
healthy volunteers: No
last name: Valérie D'Acremont, MD, PhD, MiH
role: Principal Investigator
affiliation: Swiss Tropical & Public Health Institute
facility: 
country: Tanzania
responsible party type: Principal Investigator
investigator affiliation: Swiss Tropical & Public Health Institute
investigator full name: Valérie D'Acremont
investigator title: Group leader
mesh term: Hyperthermia
mesh term: Fever