The Averting Readmissions for Malaria and Outpatient Reinfections (ARMOR) Trial

避免疟疾和门诊再感染再入院 (ARMOR) 试验

• 批准号: 10328316
• 负责人: Matthew Michael Ippolito
• 金额: $ 24.56万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-18 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10328316
• 关键词: 15 year old; Acute; Address; Adherence; Adult; Africa South of the Sahara; Antimalarials; Area; Beds; Blood; Case Management; Cessation of life; Chemoprophylaxis; Child; Childhood; Chloroguanide; Clinical; Clinical Trials; Clinical Trials Design; Documentation; Dose; Drug Kinetics; Enrollment; Entomology; Erythrocytes; Face; Falciparum Malaria; Funding; Health; Hepatic; Hospitalization; Hospitalized Child; Hospitals; Household; Human; Immunity; Incidence; Infection; Infrastructure; Inpatients; Insecticides; Intervention; Liver; Malaria; Malaria prevention; Measures; Morbidity - disease rate; Outcome; Outpatients; Parasitemia; Parasites; Participant; Patients; Pediatric Hospitals; Pharmacodynamics; Placebos; Plasmodium falciparum; Preparation; Preventive measure; Preventive treatment; Prophylactic treatment; Public Health; Randomized; Randomized Controlled Trials; Recurrence; Research; Research Personnel; Residual state; Resources; Risk; Role; Safety; Secondary Prevention; Secondary to; Site; Testing; Time; United States National Institutes of Health; Vector Ecology; Zambia; atovaquone; base; cost; decamethrin; design; effectiveness evaluation; effectiveness testing; evidence base; high risk; high risk population; hospital readmission; improved; improved outcome; indexing; infection risk; innovation; international center; mortality; novel; novel strategies; patient population; pediatric patients; prevent; primary outcome; public health priorities; readmission risk; recurrent infection; standard of care; transmission process; vector; vector control; vector mosquito

PROJECT SUMMARY/ABSTRACT Malaria due to Plasmodium falciparum is a public health priority in sub-Saharan Africa and other endemic areas, yet clinical interventions for severe malaria remain understudied. Children who survive a hospitalized episode of severe malaria remain at increased risk of morbidity and mortality for as long as 18 months post- discharge, mainly due to recurrent malaria. Thus, children who are convalescent from severe malaria represent a high-risk population who stand to benefit from interventions that prevent recurrent malaria. A small number of prior studies have tested intermittent preventive treatment-based approaches with equivocal results. We propose to test the effectiveness of a novel approach using secondary chemoprophylaxis with the causally- active antimalarial (i.e., against the liver-stage of the parasite), atovaquone-proguanil (AP), and reactive focal vector control with indoor residual spraying (rf-IRS) both alone and in combination. The objective of this proposal is to develop the study materials and prepare for the implementation of a randomized factorial design clinical trial to test the role of secondary chemoprophylaxis and reactive focal vector control in improving severe malaria outcomes during the post-discharge period where children are at high risk of hospital readmission and death due to recurrent malaria. The trial site in Nchelenge District, Zambia is a high burden area with sustained transmission throughout the year and where severe malaria accounts for up to one-third of pediatric hospital admissions at any given time. This study will leverage substantial infrastructure from the NIH- funded International Centers of Excellence for Malaria Research. The central hypothesis is that the risk of P. falciparum reinfection following an episode of severe malaria can be averted by the combination of causal prophylaxis using AP and vector control using rf-IRS. We expect that AP prophylaxis and rf-IRS will reduce morbidity and mortality in children convalescent from severe falciparum malaria. The innovation of the study includes in its use of AP for secondary chemoprophylaxis—uniquely notable for its hepatic as well as blood schizonticidal activity, in contrast to other available agents which are limited to blood-stage parasites—and a novel application of focal vector control in an understudied, high-risk population. The proposed trial is significant because it will furnish evidence to inform the case management of severe malaria which has seen little advancement in the preceding decades. It will test the effectiveness of secondary chemoprophylaxis and rf-IRS, alone and in combination, among a high-risk patient population with the potential to prevent an estimated 2.8 million rehospitalizations and over 100,000 deaths annually.

项目总结/摘要 恶性疟原虫引起的疟疾是撒哈拉以南非洲和其他地方性疾病的公共卫生优先事项。 尽管在一些地区，严重疟疾的临床干预措施仍然没有得到充分研究。住院后幸存的儿童 严重疟疾发作后18个月内发病率和死亡率仍然很高， 出院，主要是因为疟疾复发。因此，从严重疟疾中康复的儿童代表着 高危人群，他们将受益于预防疟疾复发的干预措施。一小部分 先前的研究已经测试了具有不确定结果的基于间歇性预防性治疗的方法。我们 建议测试一种新方法的有效性，使用二级化学预防与因果关系- 活性抗疟药（即，对抗寄生虫的肝脏阶段）、阿托伐醌-氯胍（AP）和反应性病灶 单独和结合使用室内滞留喷洒控制病媒。的目的 建议是开发研究材料，并为实施随机析因设计做准备 临床试验，以测试二级化学预防和反应性局灶性媒介控制在改善 出院后儿童住院风险高的严重疟疾后果 因疟疾复发而再次入院和死亡。赞比亚Nchelenge区的试验地点负担很高 严重疟疾占全球疟疾发病率的三分之一， 任何时候的儿科入院记录这项研究将利用NIH的大量基础设施， 资助的国际疟疾研究卓越中心。中心假设是P. 恶性疟原虫在严重疟疾发作后的再感染可以通过以下因素的结合来避免： 使用AP进行预防和使用rf-IRS进行病媒控制。我们预计AP预防和rf-IRS将减少 严重恶性疟疾康复期儿童的发病率和死亡率。本研究的创新点 包括AP用于继发性化疗-特别是其肝脏和血液 杀寄生虫活性，与其他仅限于血液期寄生虫的可用药剂相反， 在未充分研究的高风险人群中应用病灶向量控制的新方法。拟议的审判是 重要的是，它将提供证据，为严重疟疾的病例管理提供信息， 在过去的几十年里，进步不大。它将测试二级化学预防的有效性， rf-IRS，单独和组合，在高风险患者人群中，有可能预防 估计每年有280万人再次住院，超过10万人死亡。