Treating Brain Swelling in Pediatric Cerebral Malaria (TBS)

Michigan State University

Status and phase: Completed; Phase 3

Conditions: Malaria, Cerebral

Treatments: Drug: Hypertonic saline; Other: Mechanical ventilation

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03300648

TBS

U01AI126610 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 57 patients

Sex: All

Ages: 6 months to 12 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

57 participants in 3 patient groups

Usual care

No Intervention group

Description:

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 group

Description:

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

Treatment:

Other: Mechanical ventilation

Hypertonic saline

Experimental group

Description:

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

Treatment:

Drug: Hypertonic saline