The NICU Antibiotics and Outcomes (NANO) Trial

NICU 抗生素和结果 (NANO) 试验

• 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
• 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

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（NICU抗生素和结果）试验的目标是研究长期以来的临床实践 凭经验对新生儿极低的出生体重（ELBW）婴儿进行静脉注射抗生素。 ELBW 婴儿通常在出生后立即立即接受抗生素，然后在随后的2-3天接受抗生素 等待微生物学培养结果。通常，这些文化结果用于指导决定继续或 基于存在或不存在血液感染的抗生素。基础的假设 这种做法是，早期的抗生素给药将改善接受评估的婴儿的预后 早期败血症（EOS）。但是，没有数据可以支持或反驳这一假设，而且许多 研究表明，接受经验性抗生素（EA）的ELBW婴儿中> 98％没有EOS。最近的 微生物组研究表明，广谱抗生素暴露与逆境有关 童年的结果，这在早期细菌定殖的关键窗口中可能特别重要 在新生儿。我们根本不知道EABW婴儿早期EA是否改善健康结果，恶化 结果，或不影响结果。我们小组和其他人的数据记录了抗生素对 微生物组的发展并证明了抗生素日与A之间的剂量依赖性关联 晚期发作败血症（LOS），坏死性小肠结肠炎（NEC）或ELBW婴儿死亡的复合结果。 正式研究第一周接受EA的婴儿的不良后果事件是否更高 与接收安慰剂相比 多中心随机临床试验。我们针对的是为使用临床决定或 不使用EA是2018年最挑战的。我们将注册妊娠年龄≤28的临床上稳定的ELBW婴儿 几周，不包括具有EOS高风险的人（例如，可疑暴露于羊水内感染）和 EOS的低风险（例如，通过简单的剖腹产进行孕产妇的适应症提供）。目的 研究是（1）检验以下假设： EA与接受安慰剂的婴儿的事件有显着差异，（2）检验了以下假设。 接受EA的婴儿的第一个月生命中的粪便样本将包含较低的多样性和较高的丰度 病原体比接受安慰剂的婴儿的粪便样本和（3）比较躯体生长（每周 接受安慰剂的婴儿和婴儿的婴儿的体重和长度z得分）（探索目的）。结果 根据这项研究，可以验证有关抗生素给药的当前临床实践模式，或者它们可能 提供一个关键的理由，以进一步降低NICU中的抗生素使用情况。除了改善结果 对于个别婴儿，通过减少抗生素暴露，这种变化可以减轻全球不断增长的燃烧 抗生素耐药性和医院感染。