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：
10556361
负责人：
GRETCHEN L. BIRBECK
金额：
$ 24.55万
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/10556361
关键词：
Acetaminophen Acute Adverse effects Adverse event Affect African Age Ancillary Study Anti-Inflammatory Agents Antiinflammatory Effect Autopsy Behavior assessment Blinded Blood Blood Platelets 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 Temperature Zambia acute infection antipyretic blood product brain abnormalities cognitive testing design follow-up insight malaria infection neuroimaging neuroprotection primary outcome programs radiologist routine care scale up tool treatment as usual treatment response treatment stratification treatment-related injury

Acetaminophen Acute Adverse effects Adverse event Affect African Age Ancillary Study Anti-Inflammatory Agents Antiinflammatory Effect Autopsy Behavior assessment Blinded Blood Blood Platelets 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 Temperature Zambia acute infection antipyretic blood product brain abnormalities cognitive testing design follow-up insight malaria infection neuroimaging neuroprotection primary outcome programs radiologist routine care scale up tool treatment as usual treatment response treatment stratification treatment-related injury

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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PD/PI：Birbeck，Gretchen L. 抽象的尽管根除了努力，但约有40万名非洲儿童由于中枢神经系统疟疾而受到脑部受伤 2016年。急性疟疾感染期间较高的最高温度（TMAX）是确定的风险因素神经系统后遗症和侵袭性抗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（R01NS102176）入学，并将其扩展到赞比亚等待。在这项临床试验中，主要结果是急性感染期间的Tmax。但是，此RCT中使用的抗染料疗法可能会提供神经保护益处而不会影响TMAX-例如，例如神经保护通过抗炎机制。在这项辅助研究中，我们建议使用在RCT的背景下进行神经影像学，以进一步评估侵略性的潜在神经保护作用用于中枢神经系统疟疾的抗热热疗法并探索这些作用的可能机制。比较孩子分配给侵略性的抗热疗法，而对结构脑异常流行的常规护理从中枢神经系统疟疾中恢复后，将促进对神经保护的非狂热途径的评估。两个都赞比亚和马拉维在学术中具有高级成像的异常发展的基础设施将在恢复后1个月和12个月参加了RCT的儿童。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降低发烧有关的与治疗反应有关的变化。将评估侵略性抗热相关损伤的潜在机制，包括评估与治疗相关的中枢神经系统出血。神经影像学是一个完善的，有效的神经系统替代脑损伤，包括小儿中枢神经系统疟疾。将此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，并允许从侵略性的否则将需要长期随访进行认知和行为评估。这 MRI辅助研究添加到发烧时，RCT将提供关键的见解，可以为未来提供信息疟疾的神经保护研究可能结合成像以优化研究设计。将进行使用侵袭性抗热治疗的RCT的中心。第7页项目摘要/摘要