Clinical Trials Logo

Clinical Trial Summary

Cerebral malaria is a life-threatening complication of Plasmodium falciparum infection in African children and nonimmune travellers despite availability of quinine, the current drug of choice. Several reports have suggested that raised intracranial pressure (ICP) is a major cause of death among children with cerebral malaria. Mannitol, an osmotic diuretic, effectively lowers ICP and is used to treat post traumatic raised ICP. There have been some case reports of reduction in mortality and morbidity in African children with cerebral malaria following administration of mannitol, but as these were not randomized controlled trials it is difficult to evaluate their significance. This study seeks to establish whether a single dose of intravenous mannitol given to children with cerebral malaria will significantly reduce the coma recovery time.


Clinical Trial Description

Cerebral malaria is a life-threatening complication of Plasmodium falciparum infection accounting for significant morbidity and mortality in African children despite availability of quinine, the current drug of choice. The case fatality ranges from 5 to 40% with almost 10% of survivors experiencing neurological sequelae.

Several reports have suggested that raised intracranial pressure (ICP) may be a feature of cerebral malaria. There is evidence of brain swelling on computer tomography, magnetic resonance imaging and at necropsy. It has been postulated that raised intracranial pressure can cause death by transtentorial herniation or by compromising cerebral blood flow. In fact, most children who died of cerebral malaria in a Kenyan study, had clinical signs compatible with transtentorial herniation and all those who had severe ICP (maximum ICP > 40mmHg) either died or survived with neurological sequelae.

Mannitol, an osmotic diuretic, effectively lowers ICP and is used to treat post traumatic raised intracranial pressure. There have been some case reports of reduction in mortality and morbidity in African children with cerebral malaria following administration of mannitol, but as these were not randomized controlled trials it is difficult to evaluate their significance. Currently the WHO contends that there is insufficient evidence for using mannitol as adjunct therapy for cerebral malaria.

A recent Cochrane review found no randomized or quasi-randomized controlled trial to support or refute the use of mannitol as adjunct therapy for cerebral malaria.

Hypothesis: A single dose of intravenous mannitol (1g/kg) given to children with cerebral malaria will reduce mean coma recovery time from 22.5 to 13.1 hours.

We calculated a sample size of 78 patients in each group for 90% power and 95% confidence. In the calculation, we assumed that the children receiving intravenous mannitol would have a mean coma recovery time of 13.1 (SD 18.5) hours and those receiving placebo would have a mean coma recovery time of 22.5 (SD 18.5) hours (42.3% effect size), according to a recent study by Aceng, Byarugaba and Tumwine in the same hospital. ;


Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment


Related Conditions & MeSH terms


NCT number NCT00113854
Study type Interventional
Source Makerere University
Contact
Status Active, not recruiting
Phase Phase 3
Start date October 2004
Completion date May 2005

See also
  Status Clinical Trial Phase
Completed NCT01589289 - Rapid Diagnostic Tests and Clinical/Laboratory Predictors of Tropical Diseases in Neurological Disorders in DRC Phase 3
Active, not recruiting NCT00124267 - Efficacy of Intrarectal Versus Intravenous Quinine for the Treatment of Childhood Cerebral Malaria Phase 3
Unknown status NCT00697164 - Randomized Trial of Erythropoietin During Cerebral Malaria Phase 2/Phase 3
Completed NCT01982812 - A Dose-Escalation, Safety and Feasibility Study of Enteral LVT for Seizure Control in Pediatric CM Phase 2
Completed NCT01660672 - Enteral Levetiracetam For Seizure Control In Pediatric Cerebral Malaria Phase 1/Phase 2