Effect of Mannitol as Adjunct Therapy on the Clinical Outcome of Childhood Cerebral Malaria in Mulago Hospital: A Randomised Clinical Trial
试验速览
- 阶段
- 3 期
- 入组人数
- 156
- 试验地点
- 2
- 主要终点
- Coma recovery time (that is time from beginning of antimalarial treatment until patient has fully regained consciousness).
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double
入排标准
- 年龄范围
- 6 Months 至 5 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
结局指标
主要结局
Coma recovery time (that is time from beginning of antimalarial treatment until patient has fully regained consciousness).
次要结局
- Time taken to sit un supported
- Time to begin oral intake
- Duration of hospitalisation
- Mortality
- Proportion of children recovering with neurological sequelae