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.

项目总结/摘要 支气管肺发育不良（BPD）是30周以下出生的婴儿中最常见的不良结局 妊娠，并与不利的呼吸和神经发育结果。早期的BPD包括 肺泡和间质水肿的组成部分，导致肺顺应性降低。一些证据表明 在> 3周龄的早产儿中使用袢利尿剂，如呋塞米， 力学和氧合治疗1周后;然而，证据是薄弱的，因为大多数研究 在目前的治疗时代，没有进行广泛的表面活性剂和产前 皮质类固醇的使用和数据主要侧重于短期结果。此外，利尿剂具有一系列 副作用包括电解质异常、骨质减少、潜在耳毒性和肾钙质沉着。尽管 利尿剂的有效性和安全性缺乏证据，因此常用利尿剂。有必要 为了加强关于BPD中利尿剂使用的证据基础， 相关的临床问题-在当前的治疗时代，个体患者是否会产生短- 长期受益于治疗以及治疗是否安全有效。我们 设计了一项临床试验，解决了流行的临床态度，即一些婴儿在临床上受益或 通过包括一个导入期，该导入期使用 创新的N-of-1试验设计，同时也回答了关于长期疗效和安全性的问题， 安慰剂对照、平行组随机化的导入期N-of-1试验后的慢性利尿剂使用 慢性利尿剂治疗反应者的随机对照试验（RCT）。本R34应用程序的目的是获得 提供必要和充分的信息，以便最终决定大型临床试验的方法 通过以下具体目标：目标1：估计有反应的婴儿人数， 在N-of-1试验导入期后的平行组RCT阶段和目标2：评价提供者和 父母愿意随机分配应答者，以评估导入期和 随机化实现这些目标尤为重要，因为使用正式的N-of-1试验 设计为平行组RCT的导入期是一种独特的尖端方法。在完成这些 的目的，这个试点将提供一个详细的了解，在何种程度上，参与者能够完成 N-of-1试验，它将提供被确定为“应答者”的患者百分比的数据。这将使更多的 准确评估进入试验平行组RCT阶段的可用样本量。试点 还将提供必要的数据，以确定预期的辍学率之间的磨合和平行 由于不愿意将呋塞米或安慰剂的“应答者”随机化，一起这么 这些信息将有助于对更大的试验样本量和1个导入期中的N的设计做出明智的决定 本研究对其他计划研究利尿剂和BPD管理策略的研究具有参考价值。