Treating Brain Swelling in Pediatric Cerebral Malaria

NCT03300648 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: TBSU01AI126610
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

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.

Conditions

Malaria, Cerebral

Keywords

coma; pediatrics

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Died

  Alive or dead

  Within 7 days of randomization

Secondary Outcomes (1)

• Neurodevelopmental Disability

  1 year

Study Arms (3)

Usual care

NO INTERVENTION

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

Mechanical ventilation

EXPERIMENTAL

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

Hypertonic saline

EXPERIMENTAL

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

Interventions

Mechanical ventilation OTHER

Intubation and mechanical ventilation for a maximum of 7 days

Mechanical ventilation

Hypertonic saline DRUG

Intravenous 3 percent hypertonic saline for a maximum of 7 days

Hypertonic saline

Eligibility Criteria

• Age: 6 Months - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Michigan State University: lead
• Children's National Research Institute: collaborator
• Nationwide Children's Hospital: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• University of Maryland, Baltimore: collaborator
• Kamuzu University of Health Sciences: collaborator

Study Sites (1)

Queen Elizabeth Central Hospital

Blantyre, Malawi

Location

Related Publications (1)

• 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.

  PMID: 34020114 DERIVED

MeSH Terms

Conditions

Malaria, Cerebral; Coma

Interventions

Respiration, Artificial; Saline Solution, Hypertonic

Condition Hierarchy (Ancestors)

Central Nervous System Protozoal Infections; Central Nervous System Parasitic Infections; Central Nervous System Infections; Infections; Parasitic Diseases; Malaria; Protozoan Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Central Nervous System Diseases; Nervous System Diseases; Unconsciousness; Consciousness Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Airway Management; Therapeutics; Resuscitation; Emergency Treatment; Respiratory Therapy; Hypertonic Solutions; Solutions; Pharmaceutical Preparations

Limitations and Caveats

Low enrollment

Results Point of Contact

• Title: Terrie E. Taylor
• Organization: Michigan State University

ttmalawi@msu.edu

5178988467

Study Officials

• Terrie E Taylor, DO

  Michigan State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Investigators assessing outcome will be blinded to the arm to which the participant was randomly assigned
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Participants will be randomly assigned to one of three study arms.

Study Record Dates

• First Submitted: September 28, 2017
• First Posted: October 3, 2017
• Study Start: January 8, 2018
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: March 17, 2025
• Results First Posted: March 17, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Time Frame: Starting 6 months after publication

Locations

MA (1)