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Treating Brain Swelling in Pediatric Cerebral Malaria (TBS)

Primary Purpose

Malaria, Cerebral

Status
Recruiting
Phase
Phase 3
Locations
Malawi
Study Type
Interventional
Intervention
Mechanical ventilation
Hypertonic saline
Sponsored by
Michigan State University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malaria, Cerebral focused on measuring coma, pediatrics

Eligibility Criteria

6 Months - 12 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Peripheral P. falciparum parasitemia of any density
  • Blantyre Coma Score ≤2
  • No evidence of meningitis on lumbar puncture
  • Consciousness not regained after correction of hypoglycemia (if hypoglycemia is present)
  • Male or female whose age on the day of screening is between 6 months and 12 years old
  • Severely increased brain volume on magnetic resonance imaging
  • Provision of consent by guardian
  • Willingness to return for 1, 6, and 12 month post-randomization follow-up visits

Exclusion Criteria:

  • Gross malnutrition as evidenced by peripheral edema, hair color changes, or severe wasting
  • Advanced Human Immunodeficiency Virus (HIV) disease - defined as known HIV positive status and evidence of severe wasting
  • Evidence of recent head trauma by history or physical examination
  • Pneumonia as evidenced by oxygen saturation on room air of <85%
  • Gastroenteritis and shock as evidenced by capillary refill >3 seconds or skin tenting

Sites / Locations

  • Queen Elizabeth Central HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

No Intervention

Experimental

Experimental

Arm Label

Unual care

Mechanical ventilation

Hypertonic saline

Arm 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

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

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

Outcomes

Primary Outcome Measures

Mortality
Alive or dead

Secondary Outcome Measures

Neurodevelopmental disability
Presence and severity of neurodevelopmental disability in survivors

Full Information

First Posted
September 28, 2017
Last Updated
October 31, 2022
Sponsor
Michigan State University
Collaborators
Children's National Research Institute, Nationwide Children's Hospital, National Institute of Allergy and Infectious Diseases (NIAID), University of Maryland, Baltimore, Kamuzu University of Health Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT03300648
Brief Title
Treating Brain Swelling in Pediatric Cerebral Malaria
Acronym
TBS
Official Title
Treating Brain Swelling in Pediatric Cerebral Malaria
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 8, 2018 (Actual)
Primary Completion Date
November 30, 2023 (Anticipated)
Study Completion Date
November 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Michigan State University
Collaborators
Children's National Research Institute, Nationwide Children's Hospital, National Institute of Allergy and Infectious Diseases (NIAID), University of Maryland, Baltimore, Kamuzu University of Health Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria, Cerebral
Keywords
coma, pediatrics

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Participants will be randomly assigned to one of three study arms.
Masking
Outcomes Assessor
Masking Description
Investigators assessing outcome will be blinded to the arm to which the participant was randomly assigned
Allocation
Randomized
Enrollment
261 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Unual care
Arm Type
No Intervention
Arm 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 Title
Mechanical ventilation
Arm Type
Experimental
Arm 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 Title
Hypertonic saline
Arm Type
Experimental
Arm 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(s)
Mechanical ventilation
Intervention Description
Intubation and mechanical ventilation for a maximum of 7 days
Intervention Type
Drug
Intervention Name(s)
Hypertonic saline
Intervention Description
Intravenous 3 percent hypertonic saline for a maximum of 7 days
Primary Outcome Measure Information:
Title
Mortality
Description
Alive or dead
Time Frame
Within 7 days of randomization
Secondary Outcome Measure Information:
Title
Neurodevelopmental disability
Description
Presence and severity of neurodevelopmental disability in survivors
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Peripheral P. falciparum parasitemia of any density Blantyre Coma Score ≤2 No evidence of meningitis on lumbar puncture Consciousness not regained after correction of hypoglycemia (if hypoglycemia is present) Male or female whose age on the day of screening is between 6 months and 12 years old Severely increased brain volume on magnetic resonance imaging Provision of consent by guardian Willingness to return for 1, 6, and 12 month post-randomization follow-up visits Exclusion Criteria: Gross malnutrition as evidenced by peripheral edema, hair color changes, or severe wasting Advanced Human Immunodeficiency Virus (HIV) disease - defined as known HIV positive status and evidence of severe wasting Evidence of recent head trauma by history or physical examination Pneumonia as evidenced by oxygen saturation on room air of <85% Gastroenteritis and shock as evidenced by capillary refill >3 seconds or skin tenting
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Terrie E Taylor, DO
Phone
231-883-5948
Email
ttmalawi@msu.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Douglas G Postels, MD
Phone
505-256-4929
Email
dpostels@childrensnational.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Terrie E Taylor, DO
Organizational Affiliation
Michigan State University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Queen Elizabeth Central Hospital
City
Blantyre
Country
Malawi
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Terrie E Taylor, DO
Phone
+265 999 96 92 20
Email
ttmalawi@msu.edu
First Name & Middle Initial & Last Name & Degree
Douglas G Postels, MD
Phone
505-256-4929
Email
dpostels@childrensnational.org

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Deidentified individual participant data may be made available to other researchers
IPD Sharing Time Frame
Starting 6 months after publication
Citations:
PubMed Identifier
34020114
Citation
Postels DG. Leveling the Playing Field: Combining Pediatric Neurology and Global Health. Pediatr Neurol. 2021 Jul;120:61-62. doi: 10.1016/j.pediatrneurol.2021.04.012. Epub 2021 Apr 25. No abstract available.
Results Reference
derived

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Treating Brain Swelling in Pediatric Cerebral Malaria

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