Malaria, Cerebral
Conditions
Keywords
coma, pediatrics
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.
Interventions
OTHERMechanical ventilation
Intubation and mechanical ventilation for a maximum of 7 days
DRUGHypertonic saline
Intravenous 3 percent hypertonic saline for a maximum of 7 days
Sponsors
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
Michigan State University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Investigators assessing outcome will be blinded to the arm to which the participant was randomly assigned
Intervention model description
Participants will be randomly assigned to one of three study arms.
Eligibility
Sex/Gender
ALL
Age
6 Months to 12 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Died | Within 7 days of randomization | Alive or dead |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neurodevelopmental Disability | 1 year | Presence and severity of neurodevelopmental disability in survivors |
Countries
Malawi
Participant flow
Recruitment details
Participants recruited from 8 January 2018 through 24 May 2023. Children were recruited from Queen Elizabeth Central Hospital and were referred in from 6 surrounding District Hospitals, all in southern Malawi
Pre-assignment details
Enrolled participants underwent screening brain magnetic resonance imaging. If the images showed highly increased brain volume (brain volume scores of 6-8) they were randomized to immediate ventilation, intravenous hypertonic saline, or treatment as usual (controls)
Participants by arm
| Arm | Count |
|---|---|
| Mechanical Ventilation Intubation and mechanical ventilation at the time of randomization | 23 |
| Hypertonic Saline Treatment as usual plus continuous infusion of intravenous 3 percent hypertonic saline | 17 |
| Controls (Treatment as Usual) Treatment as usual | 17 |
| Total | 57 |
Baseline characteristics
| Characteristic | Mechanical Ventilation | Total | Controls (Treatment as Usual) | Hypertonic Saline |
|---|---|---|---|---|
| Age, Continuous | 5.1 Years STANDARD_DEVIATION 3.1 | 5.9 Years STANDARD_DEVIATION 3.3 | 6.5 Years STANDARD_DEVIATION 3.5 | 5.8 Years STANDARD_DEVIATION 4.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 23 Participants | 57 Participants | 17 Participants | 17 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Malawi | 23 participant | 57 participant | 17 participant | 17 participant |
| Sex: Female, Male Female | 8 Participants | 22 Participants | 8 Participants | 6 Participants |
| Sex: Female, Male Male | 15 Participants | 35 Participants | 9 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 23 | 5 / 17 | 5 / 17 |
| other Total, other adverse events | 0 / 23 | 0 / 17 | 0 / 17 |
| serious Total, serious adverse events | 4 / 23 | 1 / 17 | 2 / 17 |
Outcome results
Primary
Number of Participants Who Died
Alive or dead
Time frame: Within 7 days of randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mechanical Ventilation | Number of Participants Who Died | 5 Participants |
| Hypertonic Saline | Number of Participants Who Died | 5 Participants |
| Treatment as Usual | Number of Participants Who Died | 5 Participants |
Secondary
Neurodevelopmental Disability
Presence and severity of neurodevelopmental disability in survivors
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mechanical Ventilation | Neurodevelopmental Disability | 5 Participants |
| Hypertonic Saline | Neurodevelopmental Disability | 4 Participants |
| Treatment as Usual | Neurodevelopmental Disability | 1 Participants |