Treating Brain Swelling in Pediatric Cerebral Malaria (TBS)

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.

Study Overview

• Status: Completed
• Conditions: Malaria, Cerebral
• Intervention / Treatment: Other: Mechanical ventilation; Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 206
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Terrie E Taylor, DO; Phone Number: 231-883-5948; Email: ttmalawi@msu.edu
• Study Contact Backup: Name: Douglas G Postels, MD; Phone Number: 505-256-4929; Email: dpostels@childrensnational.org

Study Locations

• Malawi
  • Blantyre, Malawi
    • Queen Elizabeth Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 12 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mechanical ventilation; 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	Other: Mechanical ventilation; Intubation and mechanical ventilation for a maximum of 7 days
Experimental: Hypertonic saline; 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	Drug: Hypertonic saline; Intravenous 3 percent hypertonic saline for a maximum of 7 days
No Intervention: Usual care; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Alive or dead	Within 7 days of randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurodevelopmental disability	Presence and severity of neurodevelopmental disability in survivors	1 year

Collaborators and Investigators

• Sponsor: Michigan State University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); University of Maryland, Baltimore; Nationwide Children's Hospital; Children's National Research Institute; Kamuzu University of Health Sciences
• Investigators: Principal Investigator: Terrie E Taylor, DO, Michigan State University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2018
• Primary Completion (Actual): December 31, 2023
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: September 28, 2017
• First Submitted That Met QC Criteria: September 28, 2017
• First Posted (Actual): October 3, 2017

Study Record Updates

• Last Update Posted (Estimated): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: pediatrics; coma
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Infections; Central Nervous System Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Central Nervous System Parasitic Infections; Central Nervous System Protozoal Infections; Malaria; Brain Edema; Malaria, Cerebral
• Other Study ID Numbers: TBS; U01AI126610 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified individual participant data may be made available to other researchers
• IPD Sharing Time Frame: Starting 6 months after publication

Drug and device information, study documents

• 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