Pragmatic Research on Diuretic Management in Early BPD (PRIMED) Pilot

早期 BPD 利尿管理的实用研究 (PRIMED) 试点

• 批准号: 10590825
• 负责人: Anna Maria Hibbs
• 金额: $ 28.94万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10590825
• 关键词: Address; Adrenal Cortex Hormones; Affect; Age; Alveolar; Attitude; Belief; Birth Weight; Bronchopulmonary Dysplasia; Childhood; Chlorides; Chronic; Clinical; Clinical Trials; Data; Diuretics; Dose; Dropout; Edema; Effectiveness; Electrolytes; Eligibility Determination; Extremely Low Birth Weight Infant; Functional disorder; Furosemide; Goals; Heterogeneity; Incidence; Infant; Kidney; Liquid substance; Lung; Lung Compliance; Lung diseases; Mechanics; Meta-Analysis; National Heart, Lung, and Blood Institute; Nephrocalcinosis; Osteopenia; Outcome; Oxygen; Parents; Participant; Patients; Phase; Placebo Control; Placebos; Pregnancy; Premature Infant; Provider; Randomized; Randomized, Controlled Trials; Research; Resources; Running; Safety; Sample Size; Series; Sodium; Steroids; Strategic vision; Therapeutic; absorption; adverse outcome; antenatal; clinical practice; clinically relevant; cost; design; evidence base; improved; individual patient; infant outcome; innovation; interstitial; ototoxicity; participant enrollment; premature; respiratory; responders and non-responders; response; side effect; surfactant; symptom management; symptomatic improvement; treatment effect; trial design; willingness

PROJECT SUMMARY/ABSTRACT Bronchopulmonary dysplasia (BPD) is the most frequent adverse outcome among infants born at <30 weeks gestation and is associated with adverse respiratory and neurodevelopmental outcomes. Early BPD includes a component of alveolar and interstitial edema resulting in reduced lung compliance. Some evidence suggests that the use of loop diuretics, such as furosemide, in preterm infants > 3 weeks of age improves pulmonary mechanics and oxygenation after 1 week of treatment; however, the evidence is weak because most studies were not conducted in the current treatment era characterized by widespread surfactant and antenatal corticosteroid use and data focuses mainly on short-term outcomes. Furthermore, diuretics have a range of side effects including electrolyte abnormalities, osteopenia, potential ototoxicity, and nephrocalcinosis. Despite weak evidence for their effectiveness and concerns over safety, diuretics are commonly used. There is a need to strengthen the evidence-base regarding diuretic use in BPD with data that answers the current, relevant clinical questions—whether an individual patient in the current treatment era will derive short- term benefits from the treatment and whether the treatment is safe and effective in the long-term. We designed a clinical trial that addresses prevailing clinical attitudes that some infants clinically benefit or are “responders” by including a run-in period that examines individual patient short-term response using an innovative N-of-1 trial design while also answering questions about the longer-term efficacy and safety of chronic diuretic use by following the run-in N-of-1 trial with a placebo-controlled, parallel group randomized controlled trial (RCT) of chronic diuretics among responders. The objective of this R34 application is to obtain necessary and sufficient information to enable final decisions about the approach of the larger clinical trial through the following specific aims: Aim 1: Estimate the number of responder infants available to enter the parallel group RCT phase of the trial after the N-of-1 trial run-in period and Aim 2: Evaluate provider and parent willingness to randomize responders to assess the potential dropout rate between run-in and randomization. Accomplishing these aims is particularly important because the use of a formal N-of-1 trial design as a run-in to a parallel group RCT is a unique and cutting-edge approach. Upon completion of these aims, this pilot will provide a detailed understanding of the extent to which participants are able to complete the N-of-1 trial and it will supply data on the percent of patients identified as “responders.” This will enable a more accurate assessment of the available sample size entering the parallel group RCT phase of the trial. The pilot will also provide the data necessary to determine the expected dropout rate between the run-in and parallel group RCT phases due to reluctance to randomize a “responder” to furosemide or placebo. Together this information will enable informed decisions about the larger trial sample size and the design of the N-of-1 run-in phase, and it will be of value for others planning studies of diuretics and BPD management strategies.

项目摘要/摘要 支气管肺发育不良(BPD)是出生30周的婴儿中最常见的不良结局。 并与不良的呼吸系统和神经发育结局有关。早期的BPD包括 肺泡和间质水肿的成分，导致肺顺应性降低。一些证据表明 在3周大的早产儿中使用环状利尿剂，如速尿，可改善肺功能 治疗一周后的力学和氧合作用；然而，证据薄弱，因为大多数研究 不是在目前以广泛使用表面活性物质和产前为特征的治疗时代进行的 皮质类固醇的使用和数据主要集中在短期结果上。此外，利尿剂有一系列 副作用包括电解质异常、骨量减少、潜在的耳毒性和肾钙质沉着。尽管 利尿剂的有效性和对安全性的担忧证据不足，因此通常使用利尿剂。有必要 为了用回答当前情况的数据加强关于利尿剂在BPD中使用的证据基础， 相关的临床问题-在当前的治疗时代，单个患者是否会产生短暂的- 长期受益于治疗，以及治疗是否长期安全有效。我们 设计了一项临床试验，解决了一些婴儿临床上受益或正在受益的普遍临床态度 通过包括磨合期来检查单个患者的短期反应 创新的N-of-1试验设计，同时还回答了有关长期疗效和安全性的问题 遵循N-of-1试验的慢性利尿剂使用，采用安慰剂对照、平行随机分组 应答者中慢性利尿剂的对照试验(RCT)。此R34应用程序的目标是获得 必要和充分的信息，以便最终决定更大规模的临床试验的方法 通过以下具体目标：目标1：估计可进入 在N-of-1试验磨合期和目标2之后的平行分组随机对照试验阶段：评估提供者和 家长愿意对应答者进行随机化，以评估磨合期和退学率之间的潜在辍学率 随机化。实现这些目标特别重要，因为使用1个试验中的N个 作为一种平行群体RCT的磨合设计是一种独特的前沿方法。在完成这些任务后 AIMS，该试点将提供参与者能够在多大程度上完成 N-of-1试验，它将提供被确定为“应答者”的患者的百分比的数据。这将使更多 准确评估进入试验的平行分组随机对照试验阶段的可用样本量。飞行员 还将提供必要的数据，以确定磨合和并行之间的预期辍学率 由于不愿对速尿或安慰剂的“应答者”进行随机化而导致的随机对照试验阶段。把这个放在一起 信息将使人们能够对更大的试验样本量和1中N磨合的设计做出明智的决定 这将对其他规划利尿剂和BPD管理策略的研究有价值。