Prevention and Early Treatment of Acute Lung Injury

急性肺损伤的预防和早期治疗

• 批准号: 8705240
• 负责人: MICHAEL A. MATTHAY
• 金额: $ 14.8万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-17 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8705240
• 关键词: Academic Medical Centers; Accident and Emergency department; Acute; Acute Lung Injury; Adult Respiratory Distress Syndrome; Allogenic; Anesthesia procedures; Area; Basic Science; Bilateral; Biological; Biological Markers; Bone Marrow; California; Chest; Clinical; Clinical Protocols; Clinical Research; Clinical Trials; Clinical Trials Design; Clinical Trials Network; Collaborations; Commit; Communication; Communities; Critical Care; Critical Illness; DNA; Data; Development; Early treatment; Emergency Medicine; Enrollment; Environmental air flow; Funding; Hospitals; Human; Institution; Institutional Review Boards; Intensive Care Units; Intravenous; Location; Lung; Maps; Medical center; Medicine; Mesenchymal Stem Cells; Methods; Mucositis; National Heart, Lung, and Blood Institute; Oxygen; Participant; Patient Care; Patient Recruitments; Patients; Persons; Phase; Phase III Clinical Trials; Population; Prevention; Principal Investigator; Proteins; Protocols documentation; Recombinants; Research; Research Personnel; Risk; Safety; Sampling; San Francisco; Site; Specimen; Subgroup; Syndrome; System; Teaching Hospitals; Teleconferences; Telephone; Testing; Therapeutic; Therapeutic Agents; Universities; University Hospitals; Work; base; design; experience; keratinocyte growth factor; lung injury; meetings; mortality; novel; novel therapeutics; pre-clinical; pressure; professor; prognostic; public health relevance; respiratory; screening; symposium

DESCRIPTION (provided by applicant): This proposal from the University of California, San Francisco (UCSF) responds to RFA HL-14-014 for Clinical Centers for the Prevention and Early Treatment of Acute Lung Injury (PETAL) Network, with a commitment to enroll 40 patients annually in clinical trials based in the Emergency Departments and the Intensive Care Units. The Principal Investigator will be Michael A. Matthay, MD, Professor of Medicine & Anesthesia at UCSF and the Co-Investigator will be Greg Hendey, MD, Professor and Chair, Emergency Medicine, UCSF-Fresno. There will be four participating hospitals that have an established track record of effective communication, collaboration and patient recruitment as part of the Acute Respiratory Distress Syndrome (ARDS) Network 2: (1) UCSF Moffitt-Long Hospital, the major teaching hospital at UCSF; (2) UCSF Fresno/Community Regional Medical Center, a major medical center caring for patients in the Central Valley of California located in Fresno, CA; (3) University of California, Davis Medical Center; and (4) Stanford University Medical Center. Thus, the California Network will be comprised of four major medical centers in Northern California that draw from a total population of approximately 12 million people. Each site has an established and highly motivated research coordinator and critical care investigator with experience in ARDS Network 2. To be responsive to this RFA, each site has added an Emergency Department investigator with significant prior experience in clinical trials. In addition to our work as part of ARDS Network 2 and with Emergency Department-based clinical trials, the California Network has significant expertise that is highly relevant to the current RFA. We have a major research focus on clinical criteria to identify patients at risk for ARDS prior to the initiation of positive pressure ventilation as well as a longstanding preclinical and clinical focu on novel therapeutics for ARDS. In fact, Dr. Matthay is the Principal Investigator for an ongoing NHLBI-funded phase 1/2a clinical trial of allogeneic, bone marrow-derived human mesenchymal stem cells for patients with moderate to severe ARDS that will be completed prior to the start of the PETAL Network. We are proposing two clinical protocols, one for patients with early lung injury prior to the development of ARDS that can be identified in the Emergency Department and one for patients in the Intensive Care Unit for severe ARDS. The first protocol is a phase 3 trial to test the therapeutic value of intravenous recombinant human keratinocyte growth factor in patients with early lung injury before they have met criteria for ARDS. These patients will be primarily identified in the Emergency Departments when they have bilateral pulmonary infiltrates on the chest radiograph and the need for more than 2 liters of supplemental oxygen, but do not yet require positive pressure ventilation. The second protocol is a phase 2b trial to test the potential therapeutic value of allogeneic, bone marrow-derived human mesenchymal stem cells for the treatment of patients with moderate to severe ARDS (PaO2/FiO2 < 200 mm Hg) in the Intensive Care Unit.

描述（由申请人提供）：加利福尼亚大学旧金山大学（UCSF）的这一建议对RFA HL-14-014响应，用于预防和早期治疗急性肺损伤（Petal）网络的临床中心，并承诺每年在急诊部门和密集型服务部门和密集型护理机构中招募40名患者。首席研究员将是UCSF医学和麻醉教授Michael A. Matthay，共同研究员将是UCSF-FRESNO急诊医学教授兼主席Greg Hendey。作为急性呼吸遇险综合征（ARDS）网络的一部分，将有四家参与的医院拥有有效的沟通，协作和患者招募的既定记录：（1）UCSF的主要教学医院UCSF Moffitt-Long医院； （2）UCSF弗雷斯诺/社区区域医疗中心，这是一家主要的医疗中心，照顾加利福尼亚州弗雷斯诺的加利福尼亚中部山谷的患者； （3）加利福尼亚大学戴维斯医学中心； （4）斯坦福大学医学中心。因此，加利福尼亚网络将由北加州的四个主要医疗中心组成，这些医疗中心来自总人口约1200万人。每个站点都有一个既定且积极进取的研究协调员和具有ARDS Network 2的经验的重症监护调查员。为了响应此RFA，每个站点都增加了一个急诊科调查员，在临床试验方面具有很高的先前经验。此外 作为ARDS Network 2的一部分以及基于急诊部门的临床试验的一部分，加利福尼亚网络具有与当前RFA高度相关的重要专业知识。我们对临床标准有一项重点的研究，以识别有ARDS风险的患者 启动正压通风以及长期存在的临床前和临床重点，对ARDS的新型治疗剂。实际上，Matthay博士是一项正在进行的NHLBI资助的NHLBI资助的1/2A期临床试验的主要研究者，该试验是针对瓣网络开始之前将完成的中度至重度ARD的患者的同种异体骨髓衍生的人间充质干细胞。我们提出了两种临床方案，一种针对早期肺损伤患者的ARDS发展，可以在急诊科中鉴定出来，另一个用于重症监护病房的严重ARDS患者。第一个方案是一项第三阶段试验，用于测试早期肺损伤患者静脉注射重组人角质细胞生长因子的治疗值，然后才达到ARDS的标准。这些患者将主要在急诊室中确定双侧肺部浸润，并需要超过2升的补充氧气，但不需要正压通风。第二个方案是一项2B期试验，用于测试同种异体骨髓衍生的人间充质干细胞的潜在治疗价值，用于治疗重症监护病房中度至重度ARDS（PAO2/FIO2 <200 mm Hg）的患者。