An MRI Ancillary Study of Malaria Fever Control RCT

疟疾发热控制的 MRI 辅助随机对照试验

• 批准号: 9884625
• 负责人: GRETCHEN L. BIRBECK
• 金额: $ 31.75万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-15 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9884625
• 关键词: Acetaminophen; Acute; Adverse effects; Adverse event; Affect; African; Age; Ancillary Study; Anti-Inflammatory Agents; Antiinflammatory Effect; Autopsy; Behavior assessment; Blinded; Blood; Brain; Brain Injuries; Caring; Child; Child Care; Childhood; Clinical Treatment; Clinical Trials; Clinical Trials Data Monitoring Committees; Data; Early identification; Enrollment; Evaluation; Evolution; Fever; Future; Goals; Guidelines; Hemorrhage; Hemosiderin; Ibuprofen; Image; Infrastructure; Injury; Intervention; Intervention Trial; Intraventricular; Lesion; Link; Location; Longterm Follow-up; Magnetic Resonance Imaging; Malaria; Malawi; Mediating; Methods; Negative Finding; Neurologic; Neurological outcome; Outcome; Pathway interactions; Phase; Population; Prevalence; Property; Proxy; Randomized Controlled Trials; Recovery; Research; Research Design; Residual state; Risk; Risk Factors; Severities; Stains; Structural defect; Structure; Temperature; Zambia; acute infection; antipyretic; base; blood product; brain abnormalities; cognitive testing; design; follow-up; insight; malaria infection; neuroimaging; neuroprotection; primary outcome; programs; radiologist; response; routine care; scale up; tool; treatment as usual; treatment response; treatment-related injury

Contact PD/PI: BIRBECK, GRETCHEN L. ABSTRACT Despite eradication efforts, ~400,000 African children sustained brain injuries as a result of CNS malaria in 2016. A higher maximum temperature (Tmax) during the acute malaria infection is an established risk factor for neurologic sequelae and a randomized controlled trial (RCT) of aggressive antipyretic therapy with acetaminophen and ibuprofen began enrollment in Malawi in 2019 (R01NS102176) with expansion into Zambia pending. In this clinical trial, the primary outcome is Tmax during the acute infection. However, the antipyretic therapies used in this RCT may offer neuroprotective benefits without affecting Tmax--for example, neuroprotection through anti-inflammatory mechanisms. In this ancillary study, we propose to use neuroimaging in the context of the RCT to further evaluate the potential neuroprotective effects of aggressive antipyretic therapy for CNS malaria and explore possible mechanisms for these effects. Comparing children allocated to aggressive antipyretic therapy vs. usual care on the prevalence of structural brain abnormalities after recovery from CNS malaria will facilitate the evaluation of non-fever pathways for neuroprotection. Both Zambia and Malawi have an unusually well developed infrastructure for advanced imaging in the academic Brain MRIs will be obtained in children enrolled in the RCT at 1- and 12-months post recovery. Analyses will be completed comparing the odds of having any structural injury based upon RCT treatment allocation and based upon (Tmax) stratified by treatment allocation to assess changes specifically related to response to therapy in terms of fever reduction. Potential mechanisms of aggressive antipyretic-related injury will be evaluated including assessments for treatment-related CNS bleeds. Neuroimaging is a well-established, valid proxy for neurological outcomes after brain injury including in pediatric CNS malaria. Adding this MRI ancillary study to our fever RCT may elucidate mechanisms of treatment-associated injury and allow for early identification of neuroprotection from aggressive antipyretic use that would otherwise require long-term follow-up for cognitive and behavioral assessments. This MRI ancillary study when added to the Fever RCT will provide critical insights that could inform future neuroprotective studies of malaria that might incorporate imaging to optimize study design. centers where the RCT using aggressive antipyretic therapy will be conducted. Page 7 Project Summary/Abstract

联系PD/PI：Birbeck，Gretchen L. 摘要 尽管作出了根除努力，#年仍有约40万名非洲儿童因中枢神经系统疟疾而脑部受伤。 2016年。在急性疟疾感染期间较高的最高温度(Tmax)是确定的危险因素 神经后遗症和积极退热治疗的随机对照试验(RCT) 扑热息痛和布洛芬于2019年开始在马拉维登记(R01NS102176)，扩大到 赞比亚待定。在这项临床试验中，主要结果是急性感染期间的Tmax。然而， 这项随机对照试验中使用的退热疗法可能会在不影响Tmax的情况下提供神经保护益处--例如， 通过抗炎机制进行神经保护。在这项辅助研究中，我们建议使用 随机对照试验背景下的神经成像，以进一步评估攻击性药物的潜在神经保护作用 对中枢神经系统疟疾的解热治疗，并探索这些作用的可能机制。比较孩子们 积极退热治疗与常规治疗对脑部结构异常发生率的影响 在从中枢神经系统恢复后，疟疾将有助于对神经保护的非发热途径进行评估。两者都有 赞比亚和马拉维拥有非常发达的基础设施，可以在学术上进行先进的成像 脑部核磁共振检查将于#年进行 在康复后1个月和12个月时参加随机对照试验的儿童。分析将完成，比较 发生任何结构性损伤的几率基于随机对照试验治疗分配和(Tmax)分层 治疗分配，以评估在退烧方面与治疗反应具体相关的变化。 将评估攻击性退热相关损伤的潜在机制，包括评估 治疗相关的中枢神经系统出血。神经成像是一种公认的、有效的替代治疗后的神经学结果 脑损伤，包括儿童中枢神经系统疟疾。将这项MRI辅助研究添加到我们的发烧RCT中可能会澄清 治疗相关损伤的机制，并使早期识别神经保护免受攻击 退烧药的使用，否则需要对认知和行为评估进行长期随访。这 当将MRI辅助研究添加到Fever RCT中时，将提供关键的见解，可能会为未来提供信息 疟疾的神经保护研究，可能包括成像以优化研究设计。 中心将使用积极的退热治疗进行RCT。 第7页 项目摘要/摘要