<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/NCT03300648</url>
  </required_header>
  <id_info>
    <org_study_id>TBS</org_study_id>
    <secondary_id>U01AI126610</secondary_id>
    <nct_id>NCT03300648</nct_id>
  </id_info>
  <brief_title>Treating Brain Swelling in Pediatric Cerebral Malaria</brief_title>
  <acronym>TBS</acronym>
  <official_title>Treating Brain Swelling in Pediatric Cerebral Malaria</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Michigan State University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Children's National Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Nationwide Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Maryland, Baltimore</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Kamuzu University of Health Sciences</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Michigan State University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluates the effectiveness of two interventions in Malawian children with&#xD;
      cerebral malaria at high risk of death. One-third of the participants will receive treatment&#xD;
      as usual, one-third will receive treatment as usual and be placed on a mechanical ventilator,&#xD;
      and one-third will receive treatment as usual plus intravenous hypertonic saline.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      An important mechanism of death in children with cerebral malaria is diffuse cerebral&#xD;
      swelling, cerebral herniation, compression of the brainstem respiratory center, and&#xD;
      respiratory arrest. In those who survive their illness without specific interventions,&#xD;
      reversal of diffuse cerebral swelling is rapid.&#xD;
&#xD;
      Mechanical ventilation may help to preserve life while diffuse brain swelling diminishes.&#xD;
      Intravenous hypertonic saline may work as an osmotic diuretic, directly decreasing brain&#xD;
      swelling.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 8, 2018</start_date>
  <completion_date type="Anticipated">November 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">November 30, 2023</primary_completion_date>
  <phase>Phase 3</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>
    <intervention_model_description>Participants will be randomly assigned to one of three study arms.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>Investigators assessing outcome will be blinded to the arm to which the participant was randomly assigned</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Mortality</measure>
    <time_frame>Within 7 days of randomization</time_frame>
    <description>Alive or dead</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Neurodevelopmental disability</measure>
    <time_frame>1 year</time_frame>
    <description>Presence and severity of neurodevelopmental disability in survivors</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">261</enrollment>
  <condition>Malaria, Cerebral</condition>
  <arm_group>
    <arm_group_label>Unual care</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Hospitalization in a high dependency pediatric unit with skilled nursing, intravenous artesunate followed by oral artemisinin combination therapy, intravenous fluids, nasogastric feeding, elevation of the head of the bed by 30 degrees</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Mechanical ventilation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Hospitalization in a high dependency pediatric unit with skilled nursing, intravenous artesunate followed by oral artemisinin combination therapy, intravenous fluids, nasogastric feeding, elevation of the head of the bed by 30 degrees, along with intubation and mechanical ventilation for a maximum of 7 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Hypertonic saline</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Hospitalization in a high dependency pediatric unit with skilled nursing, intravenous artesunate followed by oral artemisinin combination therapy, intravenous fluids, nasogastric feeding, elevation of the head of the bed by 30 degrees, along with intravenous 3% hypertonic saline for a maximum of 7 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Mechanical ventilation</intervention_name>
    <description>Intubation and mechanical ventilation for a maximum of 7 days</description>
    <arm_group_label>Mechanical ventilation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hypertonic saline</intervention_name>
    <description>Intravenous 3 percent hypertonic saline for a maximum of 7 days</description>
    <arm_group_label>Hypertonic saline</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Peripheral P. falciparum parasitemia of any density&#xD;
&#xD;
          -  Blantyre Coma Score ≤2&#xD;
&#xD;
          -  No evidence of meningitis on lumbar puncture&#xD;
&#xD;
          -  Consciousness not regained after correction of hypoglycemia (if hypoglycemia is&#xD;
             present)&#xD;
&#xD;
          -  Male or female whose age on the day of screening is between 6 months and 12 years old&#xD;
&#xD;
          -  Severely increased brain volume on magnetic resonance imaging&#xD;
&#xD;
          -  Provision of consent by guardian&#xD;
&#xD;
          -  Willingness to return for 1, 6, and 12 month post-randomization follow-up visits&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Gross malnutrition as evidenced by peripheral edema, hair color changes, or severe&#xD;
             wasting&#xD;
&#xD;
          -  Advanced Human Immunodeficiency Virus (HIV) disease - defined as known HIV positive&#xD;
             status and evidence of severe wasting&#xD;
&#xD;
          -  Evidence of recent head trauma by history or physical examination&#xD;
&#xD;
          -  Pneumonia as evidenced by oxygen saturation on room air of &lt;85%&#xD;
&#xD;
          -  Gastroenteritis and shock as evidenced by capillary refill &gt;3 seconds or skin tenting&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>12 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Terrie E Taylor, DO</last_name>
    <role>Principal Investigator</role>
    <affiliation>Michigan State University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Terrie E Taylor, DO</last_name>
    <phone>231-883-5948</phone>
    <email>ttmalawi@msu.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Douglas G Postels, MD</last_name>
    <phone>505-256-4929</phone>
    <email>dpostels@childrensnational.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Queen Elizabeth Central Hospital</name>
      <address>
        <city>Blantyre</city>
        <country>Malawi</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Terrie E Taylor, DO</last_name>
      <phone>+265 999 96 92 20</phone>
      <email>ttmalawi@msu.edu</email>
    </contact>
    <contact_backup>
      <last_name>Douglas G Postels, MD</last_name>
      <phone>505-256-4929</phone>
      <email>dpostels@childrensnational.org</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Malawi</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>September 28, 2017</study_first_submitted>
  <study_first_submitted_qc>September 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 3, 2017</study_first_posted>
  <last_update_submitted>October 31, 2022</last_update_submitted>
  <last_update_submitted_qc>October 31, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Michigan State University</investigator_affiliation>
    <investigator_full_name>Terrie Taylor</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>coma</keyword>
  <keyword>pediatrics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Malaria</mesh_term>
    <mesh_term>Malaria, Cerebral</mesh_term>
    <mesh_term>Brain Edema</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Deidentified individual participant data may be made available to other researchers</ipd_description>
    <ipd_time_frame>Starting 6 months after publication</ipd_time_frame>
  </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/NCT03300648
org study id: TBS
secondary id: U01AI126610
nct id: NCT03300648
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This study evaluates the effectiveness of two interventions in Malawian children with
      cerebral malaria at high risk of death. One-third of the participants will receive treatment
      as usual, one-third will receive treatment as usual and be placed on a mechanical ventilator,
      and one-third will receive treatment as usual plus intravenous hypertonic saline.
An important mechanism of death in children with cerebral malaria is diffuse cerebral
      swelling, cerebral herniation, compression of the brainstem respiratory center, and
      respiratory arrest. In those who survive their illness without specific interventions,
      reversal of diffuse cerebral swelling is rapid.

      Mechanical ventilation may help to preserve life while diffuse brain swelling diminishes.
      Intravenous hypertonic saline may work as an osmotic diuretic, directly decreasing brain
      swelling.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Participants will be randomly assigned to one of three study arms.
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: Investigators assessing outcome will be blinded to the arm to which the participant was randomly assigned
measure: Mortality
time frame: Within 7 days of randomization
description: Alive or dead
measure: Neurodevelopmental disability
time frame: 1 year
description: Presence and severity of neurodevelopmental disability in survivors
arm group label: Unual care
arm group type: No Intervention
description: Hospitalization in a high dependency pediatric unit with skilled nursing, intravenous artesunate followed by oral artemisinin combination therapy, intravenous fluids, nasogastric feeding, elevation of the head of the bed by 30 degrees
arm group label: Mechanical ventilation
arm group type: Experimental
description: Hospitalization in a high dependency pediatric unit with skilled nursing, intravenous artesunate followed by oral artemisinin combination therapy, intravenous fluids, nasogastric feeding, elevation of the head of the bed by 30 degrees, along with intubation and mechanical ventilation for a maximum of 7 days
arm group label: Hypertonic saline
arm group type: Experimental
description: Hospitalization in a high dependency pediatric unit with skilled nursing, intravenous artesunate followed by oral artemisinin combination therapy, intravenous fluids, nasogastric feeding, elevation of the head of the bed by 30 degrees, along with intravenous 3% hypertonic saline for a maximum of 7 days
intervention type: Other
intervention name: Mechanical ventilation
description: Intubation and mechanical ventilation for a maximum of 7 days
arm group label: Mechanical ventilation
intervention type: Drug
intervention name: Hypertonic saline
description: Intravenous 3 percent hypertonic saline for a maximum of 7 days
arm group label: Hypertonic saline
criteria: 
gender: All
minimum age: 6 Months
maximum age: 12 Years
healthy volunteers: No
last name: Terrie E Taylor, DO
role: Principal Investigator
affiliation: Michigan State University
last name: Terrie E Taylor, DO
phone: 231-883-5948
email: ttmalawi@msu.edu
last name: Douglas G Postels, MD
phone: 505-256-4929
email: dpostels@childrensnational.org
facility: 
status: Recruiting
contact: 
contact backup: 
country: Malawi
responsible party type: Principal Investigator
investigator affiliation: Michigan State University
investigator full name: Terrie Taylor
investigator title: Professor
mesh term: Malaria
mesh term: Malaria, Cerebral
mesh term: Brain Edema
sharing ipd: Yes
ipd description: Deidentified individual participant data may be made available to other researchers
ipd time frame: Starting 6 months after publication