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

基本信息

批准号：
10117293
负责人：
GRETCHEN L. BIRBECK
金额：
$ 28.27万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
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/10117293
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

项目摘要

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

联系人 PD/PI：BIRBECK, GRETCHEN L. 抽象的尽管努力根除疟疾，仍有约 40 万非洲儿童因中枢神经系统疟疾而遭受脑损伤。 2016. 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系统后遗症和一项积极退热治疗的随机对照试验 (RCT) 对乙酰氨基酚和布洛芬于 2019 年开始在马拉维注册 (R01NS102176)，并扩展到赞比亚待定。在此临床试验中，主要结果是急性感染期间的 Tmax。然而，该 RCT 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作用，例如，通过抗炎机制发挥神经保护作用。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影像学，以进一步评估攻击性行为的潜在神经保护作用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。比较孩子积极退热治疗与常规护理对大脑结构异常患病率的影响中枢神经系统疟疾康复后将有助于评估神经保护的非发烧途径。两个都赞比亚和马拉维拥有异常发达的学术先进成像基础设施脑部 MRI 检查将在儿童在康复后 1 个月和 12 个月时参加了 RCT。分析将完成比较基于 RCT 治疗分配和基于 (Tmax) 分层的任何结构性损伤的几率治疗分配，以评估与退烧治疗反应特别相关的变化。将评估积极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。神经影像学是神经学结果的成熟、有效的替代指标。脑损伤，包括小儿中枢神经系统疟疾。将这项 MRI 辅助研究添加到我们的发烧 RCT 中可能会阐明治疗相关损伤的机制，并允许及早识别攻击性神经保护退烧药的使用，否则需要长期随访进行认知和行为评估。这 MRI 辅助研究添加到发热 RCT 中后将提供重要见解，为未来提供信息疟疾的神经保护研究可能会结合成像来优化研究设计。将进行使用积极退热治疗的随机对照试验的中心。第7页项目概要/摘要