Treating Brain Swelling in Pediatric Cerebral Malaria

Study Overview
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Brief Summary
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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
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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.

Official Title
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Treating Brain Swelling in Pediatric Cerebral Malaria

Conditions
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Malaria, Cerebral

Intervention / Treatment
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* Other: Mechanical ventilation
* Drug: Hypertonic saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomly assigned to one of three study arms.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Unual care<br>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<br>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<br>* Intubation and mechanical ventilation for a maximum of 7 days<br>|
| Experimental: Hypertonic saline<br>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<br>* Intravenous 3 percent hypertonic saline for a maximum of 7 days<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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coma, pediatrics