Planning grant for CMV suppression to reduce mortality in hospitalized, HIV-exposed children
为抑制巨细胞病毒(CMV)提供规划拨款,以降低感染艾滋病毒的住院儿童的死亡率
基本信息
- 批准号:10620961
- 负责人:
- 金额:$ 21.19万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-01 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AdministratorAdmission activityAdultAfrica South of the SaharaAfricanAgeAgreementAntiviral AgentsAntiviral TherapyApplications GrantsBiological MarkersBloodBudgetsCase Report FormCause of DeathCessation of lifeChildChild HealthChildhoodClinicalClinical TrialsClinical Trials Data Monitoring CommitteesCommunitiesConsentCountyCritical IllnessCytomegalovirusCytomegalovirus InfectionsDataDatabasesDependenceDetectionDevelopmentDrug KineticsEducational CurriculumEnrollmentEnsureEtiologyEuropeFutureGanciclovirGastroenteritisGoalsGovernmentGrantHIVHIV SeronegativityHealthHospitalizationHospitalized ChildHospitalsHypoxiaImmunocompetentIndividualInformation DisseminationInpatientsInstitutionIntensive CareInternationalInterventionInvestigationKenyaLaboratoriesLinkLogisticsManualsMechanical ventilationMonitorNeutropeniaObservational StudyOutcomeOutpatientsOxygenPathologicPathologyPatientsPhysiciansPlacebosPneumoniaPolicy MakerPrevalenceProceduresProphylactic treatmentProtocols documentationPublic HealthPublicationsRandomizedRandomized, Controlled TrialsResearchResearch DesignResearch PersonnelRiskRoleSafetySeminalSepsisSiteStatistical Data InterpretationTrainingTreatment EfficacyUniversitiesVentilatorViral Load resultViremiaWashingtonWomanWorkagedantiretroviral therapyclinical trial protocolcohortdata managementdesignearly childhoodhigh riskimprovedimproved outcomeinstrumentintestinal injurylung injurymaterial transfer agreementmeetingsmortalitymulti-site trialneutrophiloperationorganizational structureprimary endpointprimary outcomequality assurancerandomized trialrecruitrespiratorystandard of carewasting
项目摘要
ABSTRACT
Increasing evidence suggests the detection of cytomegalovirus (CMV) viremia during serious illness may
identify a subset of individuals at elevated risk for poor outcomes. Associations between CMV viremia and
mortality have been found in immunocompetent adults admitted to intensive care in the US and Europe, and in
children living with HIV (CLHIV) and HIV-exposed uninfected (HEU) children hospitalized in Kenya. A trial in
HIV-negative adults with severe sepsis found that randomization to ganciclovir prophylaxis reduced the risk of
CMV reactivation and decreased oxygen dependency, suggesting a potential causal link between CMV
replication and outcomes. Together these data suggest suppression of CMV viremia may improve outcomes in
severely ill patients, and our goal is to conduct a randomized controlled trial (RCT) in HIV-exposed (CLHIV and
HEU) children in Kenya, where CMV prevalence nears 100% and inpatient mortality rates for severely ill
children are ~30%. The proposed trial will enroll children aged <24 months, with CMV viremia >1000 IU/ml,
and will randomize children to receive either standard of care or antiviral therapy to suppress CMV viremia.
Primary endpoints will be 6-month all-cause mortality, risk of neutropenia, and the combined outcome of death
or continued hospitalization at 15 days. Clinical and blood biomarkers of lung and intestinal injury, and
pathological investigations will inform mechanisms of intervention efficacy.
This proposal brings together an international team of clinical and scientific experts to develop a randomized
trial which will determine whether suppression of CMV viremia using antiviral therapy is safe and reduces
mortality and other deleterious outcomes in highly vulnerable children. This Planning Period will optimally
prepare the team and sites to conduct the proposed RCT. In Aim 1 we will finalize the protocol and all study
instruments, including the statistical analysis and data management plans, data safety and monitoring plan
(DSMP), data safety and monitoring board (DSMB) and charter, development of recruitment and consent
materials, case report forms (CRFs), and a detailed grant proposal budget for the clinical trial. In Aim 2 we will
convene the study investigators, clinical and scientific advisors and key government and community
stakeholders, and to develop a roles and responsibilities plan for multisite trial coordination and results
dissemination. In Aim 3 we will finalize the Manual of Operations (MOP) and prepare the sites to implement
the clinical trial protocol. If the intervention is found to be safe and effective, the collaborative team is ideally
poised to work with Kenyan facilities and policymakers to develop further trials and/or scale the intervention.
抽象的
越来越多的证据表明在严重疾病期间发现巨细胞病毒(CMV)病毒血症可能
确定一部分患者的较差风险。 CMV病毒血症与
在美国和欧洲接受重症监护的免疫能力成年人中发现了死亡率
艾滋病毒(CLHIV)和艾滋病毒暴露未感染的(HEU)儿童在肯尼亚住院的儿童。试用
患有严重败血症的艾滋病毒阴性成年人发现,与预防的随机分组可降低
CMV重新激活并降低氧气依赖性,表明CMV之间存在潜在的因果关系
复制和结果。这些数据一起表明抑制CMV病毒血症可能会改善
严重患者患者,我们的目标是在艾滋病毒暴露(CLHIV和
HEU)在肯尼亚的儿童,CMV患病率接近100%,住院死亡率严重患病率
儿童约为30%。拟议的试验将招募<24个月的儿童,CMV病毒率> 1000 IU/mL,
并将随机儿童接受标准的护理或抗病毒疗法以抑制CMV病毒血症。
主要终点将是6个月的全因死亡率,中性粒细胞减少症的风险和死亡的综合结果
或在15天内继续住院。肺和肠损伤的临床和血液生物标志物,以及
病理研究将为干预功效的机制提供信息。
该提案汇集了一个国际临床和科学专家团队,以开发一个随机的
试验将确定使用抗病毒疗法抑制CMV病毒血症是否安全而减少
高度脆弱的儿童的死亡率和其他有害结果。这个计划期限将最佳
准备团队和站点以进行拟议的RCT。在AIM 1中,我们将最终确定协议和所有研究
工具,包括统计分析和数据管理计划,数据安全和监视计划
(DSMP),数据安全和监测委员会(DSMB)和宪章,招聘和同意的发展
材料,案例报告表(CRF)以及临床试验的详细赠款预算。在目标2中,我们将
召集研究研究人员,临床和科学顾问以及主要政府和社区
利益相关者,并制定一项角色和责任计划,以进行多站点试用协调和结果
传播。在AIM 3中,我们将最终确定操作手册(MOP),并准备实施的站点
临床试验方案。如果发现干预措施是安全有效的,那么协作团队是理想情况下
准备与肯尼亚的设施和决策者合作,以开发进一步的试验和/或扩展干预措施。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Jennifer Ann Slyker其他文献
Jennifer Ann Slyker的其他文献
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{{ truncateString('Jennifer Ann Slyker', 18)}}的其他基金
The effect of cytomegalovirus, inflammation, and immune activation on neurodevelopment in children exposed to maternal HIV infection
巨细胞病毒、炎症和免疫激活对母亲 HIV 感染儿童神经发育的影响
- 批准号:
10381037 - 财政年份:2022
- 资助金额:
$ 21.19万 - 项目类别:
CMV viremia and mortality in hospitalized HIV-infected children
住院 HIV 感染儿童的 CMV 病毒血症和死亡率
- 批准号:
9764423 - 财政年份:2018
- 资助金额:
$ 21.19万 - 项目类别:
Vertical CMV transmission in the setting of maternal HIV-1 infection in Kenya
肯尼亚孕产妇 HIV-1 感染情况下 CMV 垂直传播
- 批准号:
8488400 - 财政年份:2010
- 资助金额:
$ 21.19万 - 项目类别:
Vertical CMV transmission in the setting of maternal HIV-1 infection in Kenya
肯尼亚孕产妇 HIV-1 感染情况下 CMV 垂直传播
- 批准号:
8298902 - 财政年份:2010
- 资助金额:
$ 21.19万 - 项目类别:
Vertical CMV transmission in the setting of maternal HIV-1 infection in Kenya
肯尼亚孕产妇 HIV-1 感染情况下 CMV 垂直传播
- 批准号:
8011613 - 财政年份:2010
- 资助金额:
$ 21.19万 - 项目类别:
Vertical CMV transmission in the setting of maternal HIV-1 infection in Kenya
肯尼亚孕产妇 HIV-1 感染情况下 CMV 垂直传播
- 批准号:
8691661 - 财政年份:2010
- 资助金额:
$ 21.19万 - 项目类别:
Vertical CMV transmission in the setting of maternal HIV-1 infection in Kenya
肯尼亚孕产妇 HIV-1 感染情况下 CMV 垂直传播
- 批准号:
8098816 - 财政年份:2010
- 资助金额:
$ 21.19万 - 项目类别:
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