Aggressive antipyretics in central nervous system malaria: Study protocol of a randomized-controlled trial assessing antipyretic efficacy and parasite clearance effects (Malaria FEVER study).
Aggressive antipyretics in central nervous system malaria: Study protocol of a randomized-controlled trial assessing antipyretic efficacy and parasite clearance effects (Malaria FEVER study).
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DOI：
10.1371/journal.pone.0268414
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发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
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疟疾仍然是非洲的主要公共卫生挑战，每年约有250，000名患有疟疾的儿童经历神经损伤，随后出现神经残疾。有证据表明，急性期体温升高是感染后神经系统后遗症的危险因素。因此，在有脑损伤重大风险的复杂性疟疾儿童中，可能需要积极的解热治疗。以前的临床试验主要是在患有单纯性疟疾的儿童中进行的，并且只使用单一的解热药物，在退烧方面显示出有限的益处;然而，迄今为止还没有研究检查使用双重疗法的疟疾发热管理。在这项积极解热治疗的临床试验中，因中枢神经系统（CNS）疟疾住院的儿童将随机接受常规治疗（对乙酰氨基酚每6小时一次，体温≥ 38.5°C）与预防性对乙酰氨基酚和布洛芬每6小时一次，持续72小时。在这项双盲、安慰剂对照、双臂临床试验中，我们将从马拉维布兰太尔的伊丽莎白女王中央医院、赞比亚卢萨卡的大学教学医院儿童医院和赞比亚奇帕塔的奇帕塔中央医院三个机构招募284名参与者。父母或监护人必须提供书面知情同意书。符合条件的参与者为2-11岁，通过外周血涂片或快速诊断试验证明恶性疟原虫疟疾感染，并伴有与疟疾相关的CNS症状。合格儿童将接受治疗分配随机化，接受发热管理标准治疗或预防性计划治疗，每6小时一次，持续72小时，使用对乙酰氨基酚和布洛芬进行双重解热治疗。将采用区组随机化以1：1分配至治疗组。主要结局是入组后72小时内的最高体温。次要结局包括通过定量富组氨酸蛋白II测定的寄生虫清除率和入组后72小时内的癫痫发作。本临床试验旨在通过评价使用两种解热药和预防性给药的更积极的解热药的退热疗效，挑战基于高热的有限发热治疗的实践范式，并将阐明解热药对寄生虫清除和急性症状性癫痫发作的影响。如果积极的退热治疗被证明可以安全地降低最高体温，那么就有必要进行一项临床试验来评估降低体温对中枢神经系统疟疾的神经保护作用。
Malaria remains a major public health challenge in Africa where annually, ~250,000 children with malaria experience a neurologic injury with subsequent neuro-disability. Evidence indicates that a higher temperature during the acute illness is a risk factor for post-infectious neurologic sequelae. As such, aggressive antipyretic therapy may be warranted among children with complicated malaria at substantial risk of brain injury. Previous clinical trials conducted primarily in children with uncomplicated malaria and using only a single antipyretic medication have shown limited benefits in terms of fever reduction; however, no studies to date have examined malaria fever management using dual therapies. In this clinical trial of aggressive antipyretic therapy, children hospitalized with central nervous system (CNS) malaria will be randomized to usual care (acetaminophen every 6 hours for a temperature ≥ 38.5°C) vs. prophylactic acetaminophen and ibuprofen every 6 hours for 72 hours. In this double-blinded, placebo controlled, two-armed clinical trial, we will enroll 284 participants from three settings at Queen Elizabeth Central Hospital in Blantyre, Malawi; at the University Teaching Hospitals Children’s Hospital in Lusaka, Zambia and at Chipata Central Hospital, Chipata, Zambia. Parents or guardians must provide written informed consent. Eligible participants are 2–11 years with evidence of P. falciparum malaria infection by peripheral blood smear or rapid diagnostic test with CNS symptoms associated with malaria. Eligible children will receive treatment allocation randomization either to standard of care for fever management or to prophylactic, scheduled treatment every 6 hours for 72 hours with dual antipyretic therapies using acetaminophen and ibuprofen. Assignment to treatment groups will be with 1:1 allocation using blocked randomization. The primary outcome will be maximum temperature in the 72 hours after enrolment. Secondary outcomes include parasite clearance as determined by quantitative Histidine Rich Protein II and seizures through 72 hours after enrolment. This clinical trial seeks to challenge the practice paradigm of limited fever treatment based upon hyperpyrexia by evaluating the fever-reduction efficacy of more aggressive antipyretic using two antipyretics and prophylactic administration and will elucidate the impact of antipyretics on parasite clearance and acute symptomatic seizures. If aggressive antipyretic therapy is shown to safely reduce the maximum temperature, a clinical trial evaluating the neuroprotective effects of temperature reduction in CNS malaria is warranted.
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影响因子：
5.7
作者：
Arrich, Jasmin;Holzer, Michael;Mullner, Marcus
通讯作者：
Mullner, Marcus
影响因子：
48
作者：
Birbeck, Gretchen L.;Molyneux, Malcolm E.;Taylor, Terrie E.
通讯作者：
Taylor, Terrie E.
影响因子：
168.9
作者：
Brandts, CH;Ndjave, M;Kremsner, PG
通讯作者：
Kremsner, PG
影响因子：
7.3
作者：
CLARK, IA;MACKIE, EJ;COWDEN, WB
通讯作者：
COWDEN, WB
DOI：
10.4269/ajtmh.2010.09-0532
发表时间：
2010-02-01
影响因子：
3.3
作者：
Birbeck, Gretchen L.;Beare, Nicholas;Taylor, Terrie E.
通讯作者：
Taylor, Terrie E.