<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/NCT04473768</url>
  </required_header>
  <id_info>
    <org_study_id>ID ITM202007</org_study_id>
    <nct_id>NCT04473768</nct_id>
  </id_info>
  <brief_title>Clinical Decision Support in Non-typhoidal Salmonella Bloodstream Infections in Children</brief_title>
  <acronym>DeNTS</acronym>
  <official_title>Clinical Decision Support in Non-typhoidal Salmonella Bloodstream Infections in Children in Sub-Saharan Africa: a Prospective Cohort Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institute of Tropical Medicine, Belgium</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>KU Leuven</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hôpital St. Luc Kisantu, République Democratique du Congo</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>International Vaccine Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Institute of Tropical Medicine, Belgium</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      In sub-Saharan Africa, non-typhoidal Salmonella (NTS) are a frequent cause of bloodstream&#xD;
      infection, display high levels of antibiotic resistance and have a high case fatality rate&#xD;
      (15%). In Kisantu hospital in the Democratic Republic of Congo (DR Congo), NTS account for&#xD;
      75% of bloodstream infection in children and many children are co-infected with Plasmodium&#xD;
      falciparum (Pf) malaria. NTS bloodstream infection presents as a non-specific severe febrile&#xD;
      illness, which challenges early diagnosis and, as a consequence, prompt and appropriate&#xD;
      antibiotic treatment.Moreover, at the first level of care, frontline health workers have&#xD;
      limited expertise and diagnostic skills and, as a consequence, clinical danger signs that&#xD;
      indicate serious bacterial infections are often overlooked.&#xD;
&#xD;
      Basic handheld diagnostic instruments and point-of-care tests can help to reliably detect&#xD;
      danger signs and improve triage, referral and the start of antibiotics, but there is need for&#xD;
      field implementation and adoption to low-resource settings. Further, it is known that some&#xD;
      clinical signs and symptoms are frequent in NTS bloodstream infections. The integration of&#xD;
      these clinical signs and symptoms in a clinical decision support model can facilitate the&#xD;
      diagnosis of NTS bloodstream infections and target antibiotic treatment.&#xD;
&#xD;
      The investigators aim to develop such a clinical decision support model based on data from&#xD;
      children under five years old admitted to Kisantu district referral hospital in the&#xD;
      Democratic republic of the Congo. While developing the model, the investigators will focus on&#xD;
      the signs and symptoms that can differentiate NTS bloodstream infection from severe Pf&#xD;
      malaria and on the clinical danger signs that can be assessed by handheld diagnostic&#xD;
      instruments and point-of-care tests. The deliverable will be a clinical decision support&#xD;
      model ready to integrate in an electronic decision support system.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 1, 2021</start_date>
  <completion_date type="Actual">January 31, 2022</completion_date>
  <primary_completion_date type="Actual">January 31, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Predictive signs and symptoms</measure>
    <time_frame>12 months</time_frame>
    <description>Identify clinical signs and symptoms predictive for and differentiate between:&#xD;
1.1. NTS bloodstream infection 1.2. severe Pf malaria mono-infection 1.3. NTS/Pf malaria co-infection 1.4. other-pathogen bloodstream infections 1.5. other causes of febrile illness requiring hospital admission</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Contribution of handheld diagnostics and point-of-care tests to NTS bloodstream infection diagnosis</measure>
    <time_frame>12 months</time_frame>
    <description>Assess the contribution of handheld diagnostic instruments and point-of-care tests to the detection of danger signs associated with NTS bloodstream infection</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clinical decision support model for NTS bloodstream infection</measure>
    <time_frame>12 months</time_frame>
    <description>Develop a clinical decision support model for diagnosis of NTS bloodstream infection based on the predictive clinical signs and symptoms associated with NTS bloodstream infections</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Contribution of handheld diagnostics and point-of-care tests to bloodstream infection diagnosis</measure>
    <time_frame>12 months</time_frame>
    <description>Assess the contribution of handheld diagnostic instruments and point-of-care tests to the detection of danger signs associated with all pathogen bloodstream infection (NTS and other-pathogen bloodstream infections combined)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical decision support model for bloodstream infection</measure>
    <time_frame>12 months</time_frame>
    <description>Develop a clinical decision support model for diagnosis of bloodstream infection caused by all pathogens (NTS and other pathogens combined)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Case fatality</measure>
    <time_frame>12 months</time_frame>
    <description>Determine the clinical signs and symptoms associated with case fatality in NTS bloodstream infection and all pathogen bloodstream infections (NTS and other pathogen combined)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geographical clustering</measure>
    <time_frame>12 months</time_frame>
    <description>Assess the geographical clustering of cases with NTS bloodstream infection</description>
  </secondary_outcome>
  <number_of_groups>5</number_of_groups>
  <enrollment type="Actual">1880</enrollment>
  <condition>Bloodstream Infection</condition>
  <condition>Salmonella Bacteremia</condition>
  <condition>Malaria,Falciparum</condition>
  <condition>Severe Malaria</condition>
  <arm_group>
    <arm_group_label>NTS bloodstream infection</arm_group_label>
    <description>growth of NTS in blood culture</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NTS/Pf malaria co-infection</arm_group_label>
    <description>concurrence of current Pf malaria infection and NTS bloodstream infection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Other pathogen bloodstream infections</arm_group_label>
    <description>growth of a pathogen other than NTS in blood culture</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Severe Pf malaria mono-infection</arm_group_label>
    <description>defined according to WHO-criteria</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Other causes of febrile illness requiring hospital admission</arm_group_label>
    <description>Current Pf malaria infection: see above&#xD;
Recent Pf malaria infection: see above&#xD;
Non-confirmed bloodstream infection without Pf malaria: no growth in blood culture and negative results in all Pf malaria tests&#xD;
If feasible, severe bacterial localized infections such as pneumonia, meningitis, osteomyelitis, complicated urinary tract infection, abscess, skin/soft tissue infection or abdominal infection, will be assessed and clinically defined</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Study site: Pediatric ward of St. Luc general referral hospital in Kisantu health zone&#xD;
        (Province Kongo Central, DR Congo), further referred to as &quot;Kisantu Hospital&quot;&#xD;
&#xD;
          -  Capacity: 100 beds, bed occupancy reaches up to 180%&#xD;
&#xD;
          -  Financial system: Flat fees per admission (10$)&#xD;
&#xD;
          -  Ongoing blood culture surveillance study:&#xD;
&#xD;
               -  Routine free-of-charge blood culture sampling &amp; work-up coordinated by INRB/ITM&#xD;
&#xD;
               -  Since 2017, blood culture surveillance as a part of typhoid conjugate vaccine&#xD;
                  study&#xD;
&#xD;
          -  Epidemiological context:&#xD;
&#xD;
               -  High burden of non-typhoidal Salmonella (NTS) bloodstream infections&#xD;
&#xD;
               -  High Plasmodium falciparum (Pf) malaria endemicity&#xD;
&#xD;
               -  High prevalence of malnutrition&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Be a child of &gt; 28 days and &lt; 5 years old&#xD;
&#xD;
          2. Be admitted to Kisantu Hospital&#xD;
&#xD;
          3. Having a blood cultured sampled according to the criteria for suspected bloodstream&#xD;
             infection embedded in the blood culture surveillance, i.e. presence of objective&#xD;
             fever, hypothermia or history of fever during past 48 hours + at least one of the&#xD;
             following criteria:&#xD;
&#xD;
               -  Hypotension, confusion or increased respiratory rate&#xD;
&#xD;
               -  Suspicion of severe localized infection: pneumonia, meningitis, osteomyelitis,&#xD;
                  complicated urinary tract infection, abscess, skin/soft tissue infection or&#xD;
                  abdominal infection&#xD;
&#xD;
               -  Suspicion of typhoid fever&#xD;
&#xD;
               -  Suspicion of severe Pf malaria&#xD;
&#xD;
          4. Having a caregiver willing and able to provide written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  None&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>28 Days</minimum_age>
    <maximum_age>5 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bieke Tack, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institute of Tropical Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Kisantu general referral hospital</name>
      <address>
        <city>Antwerp</city>
        <zip>2000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>July 13, 2020</study_first_submitted>
  <study_first_submitted_qc>July 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 16, 2020</study_first_posted>
  <last_update_submitted>April 4, 2022</last_update_submitted>
  <last_update_submitted_qc>April 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 5, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Bloodstream infection</keyword>
  <keyword>Salmonella non-typhi</keyword>
  <keyword>Children under five years</keyword>
  <keyword>Clinical decision support</keyword>
  <keyword>Democratic Republic of the Congo</keyword>
  <keyword>Fever</keyword>
  <keyword>Febrile illness</keyword>
  <keyword>Malaria</keyword>
  <keyword>Anemia</keyword>
  <keyword>Malnutrition</keyword>
  <keyword>Bacterial infection</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Malaria</mesh_term>
    <mesh_term>Bacteremia</mesh_term>
    <mesh_term>Sepsis</mesh_term>
    <mesh_term>Malaria, Falciparum</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04473768
org study id: ID ITM202007
nct id: NCT04473768
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
In sub-Saharan Africa, non-typhoidal Salmonella (NTS) are a frequent cause of bloodstream
      infection, display high levels of antibiotic resistance and have a high case fatality rate
      (15%). In Kisantu hospital in the Democratic Republic of Congo (DR Congo), NTS account for
      75% of bloodstream infection in children and many children are co-infected with Plasmodium
      falciparum (Pf) malaria. NTS bloodstream infection presents as a non-specific severe febrile
      illness, which challenges early diagnosis and, as a consequence, prompt and appropriate
      antibiotic treatment.Moreover, at the first level of care, frontline health workers have
      limited expertise and diagnostic skills and, as a consequence, clinical danger signs that
      indicate serious bacterial infections are often overlooked.

      Basic handheld diagnostic instruments and point-of-care tests can help to reliably detect
      danger signs and improve triage, referral and the start of antibiotics, but there is need for
      field implementation and adoption to low-resource settings. Further, it is known that some
      clinical signs and symptoms are frequent in NTS bloodstream infections. The integration of
      these clinical signs and symptoms in a clinical decision support model can facilitate the
      diagnosis of NTS bloodstream infections and target antibiotic treatment.

      The investigators aim to develop such a clinical decision support model based on data from
      children under five years old admitted to Kisantu district referral hospital in the
      Democratic republic of the Congo. While developing the model, the investigators will focus on
      the signs and symptoms that can differentiate NTS bloodstream infection from severe Pf
      malaria and on the clinical danger signs that can be assessed by handheld diagnostic
      instruments and point-of-care tests. The deliverable will be a clinical decision support
      model ready to integrate in an electronic decision support system.
observational model: Cohort
time perspective: Prospective
measure: Predictive signs and symptoms
time frame: 12 months
description: Identify clinical signs and symptoms predictive for and differentiate between:
1.1. NTS bloodstream infection 1.2. severe Pf malaria mono-infection 1.3. NTS/Pf malaria co-infection 1.4. other-pathogen bloodstream infections 1.5. other causes of febrile illness requiring hospital admission
measure: Contribution of handheld diagnostics and point-of-care tests to NTS bloodstream infection diagnosis
time frame: 12 months
description: Assess the contribution of handheld diagnostic instruments and point-of-care tests to the detection of danger signs associated with NTS bloodstream infection
measure: Clinical decision support model for NTS bloodstream infection
time frame: 12 months
description: Develop a clinical decision support model for diagnosis of NTS bloodstream infection based on the predictive clinical signs and symptoms associated with NTS bloodstream infections
measure: Contribution of handheld diagnostics and point-of-care tests to bloodstream infection diagnosis
time frame: 12 months
description: Assess the contribution of handheld diagnostic instruments and point-of-care tests to the detection of danger signs associated with all pathogen bloodstream infection (NTS and other-pathogen bloodstream infections combined)
measure: Clinical decision support model for bloodstream infection
time frame: 12 months
description: Develop a clinical decision support model for diagnosis of bloodstream infection caused by all pathogens (NTS and other pathogens combined)
measure: Case fatality
time frame: 12 months
description: Determine the clinical signs and symptoms associated with case fatality in NTS bloodstream infection and all pathogen bloodstream infections (NTS and other pathogen combined)
measure: Geographical clustering
time frame: 12 months
description: Assess the geographical clustering of cases with NTS bloodstream infection
arm group label: NTS bloodstream infection
description: growth of NTS in blood culture
arm group label: NTS/Pf malaria co-infection
description: concurrence of current Pf malaria infection and NTS bloodstream infection
arm group label: Other pathogen bloodstream infections
description: growth of a pathogen other than NTS in blood culture
arm group label: Severe Pf malaria mono-infection
description: defined according to WHO-criteria
arm group label: Other causes of febrile illness requiring hospital admission
description: Current Pf malaria infection: see above
Recent Pf malaria infection: see above
Non-confirmed bloodstream infection without Pf malaria: no growth in blood culture and negative results in all Pf malaria tests
If feasible, severe bacterial localized infections such as pneumonia, meningitis, osteomyelitis, complicated urinary tract infection, abscess, skin/soft tissue infection or abdominal infection, will be assessed and clinically defined
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 28 Days
maximum age: 5 Years
healthy volunteers: No
last name: Bieke Tack, MD
role: Principal Investigator
affiliation: Institute of Tropical Medicine
facility: 
country: Belgium
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Malaria
mesh term: Bacteremia
mesh term: Sepsis
mesh term: Malaria, Falciparum
sharing ipd: Undecided