Mannitol as Adjunct Therapy for Childhood Cerebral Malaria
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00113854|
Recruitment Status : Unknown
Verified June 2005 by Makerere University.
Recruitment status was: Active, not recruiting
First Posted : June 13, 2005
Last Update Posted : June 24, 2005
|First Submitted Date ICMJE||June 10, 2005|
|First Posted Date ICMJE||June 13, 2005|
|Last Update Posted Date||June 24, 2005|
|Study Start Date ICMJE||October 2004|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||Coma recovery time (that is time from beginning of antimalarial treatment until patient has fully regained consciousness).|
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||No Changes Posted|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Mannitol as Adjunct Therapy for Childhood Cerebral Malaria|
|Official Title ICMJE||Effect of Mannitol as Adjunct Therapy on the Clinical Outcome of Childhood Cerebral Malaria in Mulago Hospital: A Randomised Clinical Trial|
|Brief 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.|
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 Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 3|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
|Condition ICMJE||Cerebral Malaria|
|Intervention ICMJE||Drug: Mannitol|
|Study Arms ICMJE||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Unknown status|
|Original Enrollment ICMJE||Same as current|
|Study Completion Date ICMJE||May 2005|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages ICMJE||6 Months to 5 Years (Child)|
|Accepts Healthy Volunteers ICMJE||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Uganda|
|Removed Location Countries|
|NCT Number ICMJE||NCT00113854|
|Other Study ID Numbers ICMJE||HD200211/246|
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||Makerere University|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|PRS Account||Makerere University|
|Verification Date||June 2005|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP