1/1: ARREST RESPIRATORY FAILURE DUE TO PNEUMONIA (ARREST PNEUMONIA)

1/1：因肺炎导致呼吸衰竭（逮捕肺炎）

• 批准号: 10266183
• 负责人: Emir Festic
• 金额: $ 206.48万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-23 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10266183
• 关键词: Accident and Emergency department; Acute; Acute respiratory failure; Adrenal Cortex Hormones; Adult Respiratory Distress Syndrome; Agonist; Alveolar; Angiopoietin-2; Antibiotics; Biologic Characteristic; Biological; Biological Markers; Budesonide; Cannulas; Cessation of life; Clinic; Clinical; Clinical Trials; Controlled Clinical Trials; Critical Care; Disease Progression; Double-Blind Method; Early Intervention; Early treatment; Endothelium; Enrollment; Etiology; Funding; Future; Gene Expression Profile; Heterogeneity; Hospitalization; Hour; Hypoxemia; Immune response; Inflammasome; Inflammation; Inhalation; Inhalation Therapy; Injury; Interleukin-6; Length of Stay; Measures; Mechanical ventilation; Medical Care Costs; Medicine; Mission; National Heart, Lung, and Blood Institute; Nebulizer; Nose; Outcome; Oxygen; Patients; Pharmaceutical Preparations; Phase; Placebos; Pneumonia; Pneumonia Severity Index; Population; Prevention; Protocols documentation; Pulmonary Edema; Randomized; Randomized Clinical Trials; Relative Risks; Respiratory Failure; Risk; Risk Factors; Risk Reduction; Saline; Severities; Shock; Societies; Sterility; Steroids; Subgroup; Supportive care; Systemic Therapy; Time; Treatment Efficacy; United States; Vascular Permeabilities; Viral; active method; aerosolized; alveolar epithelium; comorbidity; comorbidity Index; design; early phase clinical trial; formoterol; high risk; improved; inflammatory marker; injury prevention; innovation; insight; interest; lung injury; meetings; optimal treatments; preservation; prevent; prognostic; response; standard of care; supplemental oxygen; treatment as usual; treatment effect; treatment risk; ventilation

PROJECT SUMMARY/ABSTRACT: AIMS: The enclosed proposal outlines a phase III multicenter randomized clinical trial to establish the efficacy of early treatment with an inhaled corticosteroid combined with a beta-agonist vs. usual care for prevention of acute respiratory failure from pneumonia. This trial builds closely upon our recently completed NHLBI-funded Lung Injury Prevention Study with Budesonide and a Beta-agonist (LIPS-B) demonstrating that early treatment with aerosolized budesonide (a corticosteroid) and formoterol (a beta-agonist) improved oxygenation and reduced acute respiratory failure (ARF) in high-risk patients in the emergency department. The current trial will enroll 600 patients across 10 academic centers in U.S. and be conducted within the Discovery Network of the Society of Critical Care Medicine. Secondary aims will explore risk factors for respiratory failure and potential heterogenous treatment effects (HTE) in clinically and biologically defined subgroups. SIGNIFICANCE: Pneumonia is the leading infectious cause of hospitalization and death in the United States. Currently, other than antibiotics and supportive care, no established treatments directly target the lung injury that occurs with severe pneumonia. However, corticosteroids have been shown to reduce inflammation and preserve alveolar barrier function, while beta-agonists increase resorption of pulmonary edema and preserve vascular permeability—potentially crucial functions in preventing ARF in patients with pneumonia. Our recently completed phase IIa clinic trial suggest benefit of inhaled corticosteroids combined a beta-agonist. A trial to establish efficacy of these therapies, and to inform optimal treatment of patients hospitalized for pneumonia, is both timely and of critical importance to the mission of the NHLBI. INNOVATION: This trial will continue the critical innovation of early intervention to prevent disease progression in LIPS-B. Previous trials of beta- agonists and systemic steroids failed to show clinic benefits in mechanically ventilated patients with established ARDS. LIPS-B delivered aerosolized study drug within a median of 9 hours from presentation and prior to ARF, and demonstrated improved oxygenation and lower rates of ARF. We suspect that both early treatment and inhaled delivery are critical innovations responsible for these encouraging results. IMPACT: If we establish efficacy of these safe, inexpensive, and widely available medications, we will dramatically impact treatment of a major cause of hospitalization and death. Regardless of the trial’s results, our exploratory secondary aim will inform design of future trials in a field of special interest to the NHLBI.

项目摘要/摘要： 目的：封闭的提案概述了III期多中心随机临床试验，以建立效率 用遗传性皮质类固醇与β激动剂和通常的护理相结合的早期治疗 肺炎急性呼吸衰竭。该试验与我们最近完成的NHLBI资助紧密建立 肺损伤预防布德索尼和β-激动剂（LIPS-B）证明了早期治疗 用雾化的布德索尼（皮质类固醇）和福莫特罗（β-激动剂）改善了氧合和 急诊科高危患者的急性呼吸衰竭（ARF）减少。当前的审判将 在美国10个学术中心招募600名患者，并在发现网络中进行 重症监护学会。次要目的将探索呼吸衰竭和潜力的风险因素 在临床和生物学定义的亚组中的异质治疗效应（HTE）。意义： 肺炎是美国住院和死亡的主要传染病。目前，其他 比抗生素和支持护理，没有建立的治疗直接针对的肺损伤 严重的肺炎。然而，已经证明皮质类固醇可减少感染并保留肺泡 屏障功能，而β激动剂增加肺水肿的分辨率并保存血管 渗透性 - 预防肺炎患者ARF的重要功能。我们最近 完成的IIA期临床试验表明，遗传性皮质类固醇的好处将β-激动剂结合在一起。试用 确立这些疗法的有效性，并为住院治疗的肺炎的患者提供最佳治疗 及时和至关重要的是NHLBI的使命。创新：该审判将继续 早期干预的批判性创新，以防止LIPS-B疾病进展。以前的β- 激动剂和系统的立体定子未能显示出机械通风患者的临床益处 已建立的Ards。 Lips-B在表现出来的9小时内提供了雾化的研究药物， 在进行ARF之前，并显示出改善的氧合和较低的ARF速率。我们怀疑两个 治疗和继承的交付是负责这些令人鼓舞的结果的关键创新。影响：如果 我们确定了这些安全，廉价且可广泛使用的药物的有效性，我们将极大地影响 治疗住院和死亡的主要原因。不管试验的结果如何，我们的探索性 次要目标将为NHLBI特别感兴趣的未来试验设计提供信息。