TBS: Treating Brain Swelling in Pediatric Cerebral Malaria

• Sponsor: Michigan State University (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT03300648
• Collaborator: Children's National Research Institute (Other), Nationwide Children's Hospital (Other), National Institute of Allergy and Infectious Diseases (NIAID) (NIH), University of Maryland, Baltimore (Other), University of Malawi College of Medicine (Other)
• Enrollment: 261
• Location: 1
• Arms: 3
• Anticipated Duration (Months): 70.7
• Patients Per Site Per Month: 3.7

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Malaria, Cerebral	Other: Mechanical ventilation; Drug: Hypertonic saline	Phase 3

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 261 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Participants will be randomly assigned to one of three study arms.Participants will be randomly assigned to one of three study arms.
• Masking: Single (Outcomes Assessor)
• Masking Description: Investigators assessing outcome will be blinded to the arm to which the participant was randomly assigned
• Primary Purpose: Treatment
• Official Title: Treating Brain Swelling in Pediatric Cerebral Malaria
• Actual Study Start Date: Jan 8, 2018
• Anticipated Primary Completion Date: Nov 30, 2023
• Anticipated Study Completion Date: Nov 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Unual 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
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

Outcome Measures

Primary Outcome Measures

1. Mortality [Within 7 days of randomization]

   Alive or dead

Secondary Outcome Measures

1. Neurodevelopmental disability [1 year]

   Presence and severity of neurodevelopmental disability in survivors

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Months to 12 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Queen Elizabeth Central Hospital	Blantyre		Malawi

Sponsors and Collaborators

• Michigan State University
• Children's National Research Institute
• Nationwide Children's Hospital
• National Institute of Allergy and Infectious Diseases (NIAID)
• University of Maryland, Baltimore
• University of Malawi College of Medicine

Investigators

• Principal Investigator: Terrie E Taylor, DO, Michigan State University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Terrie Taylor, Professor, Michigan State University
• ClinicalTrials.gov Identifier: NCT03300648
• Other Study ID Numbers: TBS; U01AI126610
• First Posted: Oct 3, 2017
• Last Update Posted: Feb 21, 2020
• Last Verified: Feb 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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
• Keywords provided by Terrie Taylor, Professor, Michigan State University: coma; pediatrics
• Additional relevant MeSH terms: Malaria; Malaria, Cerebral; Brain Edema

Study Results

No Results Posted as of Feb 21, 2020