Mannitol as Adjunct Therapy for Childhood Cerebral Malaria

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2005 by Makerere University.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
Makerere University
ClinicalTrials.gov Identifier:
NCT00113854
First received: June 10, 2005
Last updated: June 23, 2005
Last verified: June 2005
  Purpose

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.


Condition Intervention Phase
Cerebral Malaria
Drug: Mannitol
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Effect of Mannitol as Adjunct Therapy on the Clinical Outcome of Childhood Cerebral Malaria in Mulago Hospital: A Randomised Clinical Trial

Resource links provided by NLM:


Further study details as provided by Makerere University:

Primary Outcome Measures:
  • Coma recovery time (that is time from beginning of antimalarial treatment until patient has fully regained consciousness).

Secondary Outcome Measures:
  • Time taken to sit un supported
  • Time to begin oral intake
  • Duration of hospitalisation
  • Mortality
  • Proportion of children recovering with neurological sequelae

Estimated Enrollment: 156
Study Start Date: October 2004
Estimated Study Completion Date: May 2005
Detailed 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.

  Eligibility

Ages Eligible for Study:   6 Months to 5 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Children aged 6 months to 5 years admitted to the Mulago hospital acute care unit during the study period with cerebral malaria: (seizures and unarousable coma lasting more than 30 minutes after seizures have stopped, with asexual forms of P. falciparum on the blood film, with no other cause of coma) and whose carers gave informed consent.

Exclusion Criteria:

  • Children with evidence of having received any sedation within two hours prior to admission to the acute care unit.
  • Also exclude children with clinical signs of pulmonary congestion, or heart failure, or renal disease, or shock
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00113854

Locations
Uganda
Department of Paediatrics and Child Health, Makerere Medical School
Kampala, Uganda, P O Box 7072
Sponsors and Collaborators
Makerere University
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00113854     History of Changes
Other Study ID Numbers: HD200211/246
Study First Received: June 10, 2005
Last Updated: June 23, 2005
Health Authority: Uganda: National Council for Science and Technology

Keywords provided by Makerere University:
cerebral
malaria
children
mannitol
adjunct
therapy
Uganda

Additional relevant MeSH terms:
Malaria
Malaria, Cerebral
Protozoan Infections
Parasitic Diseases
Central Nervous System Protozoal Infections
Central Nervous System Parasitic Infections
Malaria, Falciparum
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases
Mannitol
Diuretics, Osmotic
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014