The NICU Antibiotics and Outcomes (NANO) Trial

NICU 抗生素和结果 (NANO) 试验

基本信息

批准号：
10018511
负责人：
Anup C Katheria
金额：
$ 50.87万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-13 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10018511
关键词：
Adopted Adverse effects Adverse event Ampicillin Anaerobic Bacteria Antibiotic Resistance Antibiotic Therapy Antibiotics Award Biological Markers Birth Blinded Caring Cesarean section Cessation of life Childhood Clinical Clinical Practice Patterns Clinical Trials Data Development Disease Dose Early Diagnosis Eligibility Determination Enrollment Evaluation Exposure to Extremely Low Birth Weight Infant Face Fever Gentamicins Gestational Age Goals Growth Guidelines Health Hospitals Incidence Individual Infant Intravenous Length Life Membrane Microbiology Monitor Multi-Institutional Clinical Trial Necrotizing Enterocolitis Newborn Infant Nosocomial Infections Outcome Patients Pattern Physicians Physiological Placebos Population Population Study Positioning Attribute Premature Infant Premature Labor Provider Publishing Randomized Randomized Clinical Trials Recording of previous events Resistance Respiratory Failure Respiratory physiology Risk Rupture Sampling Sepsis Site Testing Time Translating Weight adverse outcome arm base care providers clinical practice design early onset experience gut microbiota hemodynamics human microbiota improved improved outcome intraamniotic infection intrapartum late onset sepsis microbial microbiome microbiome research microbiota mortality multidisciplinary pathogen perinatal complications preterm premature rupture of membranes standard of care

项目摘要

ABSTRACT The goal of the NANO (NICU Antibiotics and Outcomes) Trial is to study the longstanding clinical practice of empirically administering intravenous antibiotics to newborn extremely low birthweight (ELBW) infants. ELBW infants commonly receive antibiotics immediately after birth and then for 2-3 subsequent days while clinicians await microbiology culture results. Typically, these culture results are used to guide a decision to continue or discontinue antibiotics based on the presence or absence of a bloodstream infection. The assumption underlying this practice is that early antibiotic administration will improve outcomes in infants undergoing evaluation for early onset sepsis (EOS). However, there are no data to support or refute this assumption, and numerous studies have shown that >98% of ELBW infants receiving empiric antibiotics (EA) do not have EOS. Recent microbiome research has demonstrated that broad-spectrum antibiotic exposure is associated with adverse childhood outcomes, and this may be particularly relevant during a critical window of early bacterial colonization in newborns. We simply do not know whether early EA for ELBW infants improves health outcomes, worsens outcomes, or does not affect outcomes. Data from our group and others document the impact of antibiotics on microbiome development and demonstrate a dose-dependent association between antibiotic days and a composite outcome of late onset sepsis (LOS), necrotizing enterocolitis (NEC), or death in ELBW infants. To formally study whether the incidence of adverse outcomes is higher in infants receiving EA in the first week of life compared to babies receiving placebo, we propose the NANO Trial, an 802-subject placebo-controlled multicenter randomized clinical trial. We target a population of infants for whom the clinical decision to use or not use EA is most challenging in 2018. We will enroll clinically stable ELBW infants with gestational age ≤28 weeks, excluding those at high risk for EOS (e.g. suspected exposure to intraamniotic infection) and those at low risk for EOS (e.g. delivery via uncomplicated caesarean section for maternal indications). The aims of the study are (1) To test the hypothesis that the composite incidence of LOS, NEC, or death in infants that receive EA is significantly different than the incidence among infants that receive placebo, (2) To test the hypothesis that fecal samples in the first month of life from infants receiving EA will contain lower diversity and higher abundance of pathogens than fecal samples from infants receiving placebo, and (3) To compare somatic growth (weekly weight and length z-scores) in infants receiving EA and infants receiving placebo (exploratory aim). The results from this study may validate current clinical practice patterns regarding antibiotic administration, or they may provide a critical rationale for further reducing antibiotic usage in the NICU. In addition to improving outcomes for individual babies by reducing antibiotic exposure, such a change could mitigate the growing worldwide burden of antibiotic resistance and nosocomial infections.

抽象的 NANO（新生儿重症监护病房抗生素和结果）试验的目标是研究长期的临床实践对新生儿极低出生体重（ELBW）婴儿进行经验性静脉注射抗生素治疗。婴儿通常在出生后立即接受抗生素治疗，然后在随后的 2-3 天内接受抗生素治疗等待微生物培养结果通常，这些培养结果用于指导继续或继续的决定。根据是否存在血流感染停用抗生素。这种做法是，早期给予抗生素将改善接受评估的婴儿的结果然而，没有数据支持或反驳这一假设，并且有大量数据。研究表明，>98% 接受经验性抗生素 (EA) 的 ELBW 婴儿近期没有出现 EOS。微生物组研究表明，接触广谱抗生素与不良反应相关儿童结局，这在早期细菌定植的关键窗口期可能特别相关我们根本不知道 ELBW 婴儿的早期 EA 是否会改善或恶化健康结果。我们小组和其他人的数据记录了抗生素对结果的影响。微生物组的发育并证明抗生素使用天数和使用剂量之间存在剂量依赖性关联 ELBW 婴儿迟发性败血症 (LOS)、坏死性小肠结肠炎 (NEC) 或死亡的复合结局。正式研究第一周接受 EA 的婴儿不良后果的发生率是否较高与接受安慰剂的婴儿相比，我们提出了 NANO 试验，这是一项 802 名受试者接受安慰剂对照的试验我们针对临床决定使用或使用的婴儿群体进行多中心随机临床试验。不使用EA是2018年最具挑战性的。我们将招募胎龄≤28岁、临床稳定的ELBW婴儿周，不包括 EOS 高风险人群（例如疑似暴露于羊膜内感染）和 EOS 风险较低（例如，针对产妇适应症通过简单的剖腹产分娩）。研究的目的是 (1) 检验以下假设：接受治疗的婴儿中 LOS、NEC 或死亡的复合发生率 EA 的发生率与接受安慰剂的婴儿显着不同，(2) 检验以下假设：接受 EA 治疗的婴儿在出生第一个月的粪便样本将包含较低的多样性和较高的丰度与接受安慰剂的婴儿的粪便样本相比，病原体的数量，以及（3）比较体细胞生长（每周接受 EA 的婴儿和接受安慰剂的婴儿的体重和身长 z 分数（探索性目标）。这项研究的结果可能会验证当前有关抗生素给药的临床实践模式，或者它们可能除了改善结果之外，还为进一步减少新生儿重症监护室抗生素的使用提供了重要依据。对于个别婴儿来说，通过减少抗生素接触，这种改变可以减轻全球日益增长的负担抗生素耐药性和医院感染。