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）是婴儿小于30周的婴儿中最常的广告结果 妊娠，与不良呼吸和神经发育结果有关。早期的BPD包括 牙槽和间质性水肿的成分导致肺依从性降低。一些证据表明 在早产儿中使用循环利尿剂（例如速尿）> 3周，可以改善肺部 治疗1周后的力学和氧合；但是，证据很弱，因为大多数研究 不是在当前的治疗时代进行的，其特征是宽度表面活性剂和触角 皮质类固醇的使用和数据主要集中在短期结局上。此外，利尿剂有很多 副作用包括电解质异常，骨质减少症，潜在耳毒性和肾球身及病。尽管 通常使用利尿剂证明其有效性和对安全性的担忧。有需要 为了加强有关BPD中利尿剂使用的证据库，并通过回答当前的数据， 相关临床问题 - 当前治疗时代的个体患者是否会导致短暂 术语从治疗中受益，以及治疗是否长期安全有效。我们 设计了一项临床试验，该试验解决了一些婴儿在临床上受益或 “响应者”通过包括一个磨合期，该期间检查个人患者的短期反应 创新的N-1-1试验设计，同时还回答了有关长期有效性和安全性的问题 通过安慰剂对照，平行组随机进行慢性利尿剂的使用 响应者中慢性利尿剂的对照试验（RCT）。该R34应用的目的是获得 必要和足够的信息以实现有关大型临床试验方法的最终决定 通过以下特定目的：目标1：估计可用于输入的响应者的数量 N-1-1试验违规期和AIM 2之后的平行组RCT阶段2：评估提供商和 父母愿意随机响应者评估磨合和之间的潜在辍学率 随机化。实现这些目标尤其重要，因为使用正式的N-1-of-1试验 设计作为平行组RCT的磨合是一种独特而尖端的方法。这些完成后 目的，该飞行员将详细了解参与者能够完成的程度 N-1-1试验将提供有关被确定为“反应者”的患者百分比的数据。这将使更多 准确评估可用样本量进入试验的平行组RCT阶段。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 由于不愿随机将“响应者”随机到速尿或安慰剂而导致的组RCT相。在一起 信息将实现有关较大的试用样本量和N-1-1磨合的设计的明智决定 阶段，这对于其他计划研究利尿剂和BPD管理策略的研究将是有价值的。