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）：本提案来自加州大学旧金山分校弗朗西斯科（UCSF），旨在响应急性肺损伤预防和早期治疗临床中心（PETAL）网络的RFA HL-14 - 014，承诺每年在急诊科和重症监护室的临床试验中招募40例患者。主要研究者为Michael A。Matthay，医学博士，UCSF医学与麻醉教授，共同研究者将是Greg Hendey，医学博士，UCSF-弗雷斯诺急诊医学教授兼主席。作为急性呼吸窘迫综合征（ARDS）网络2的一部分，将有四家参与医院在有效沟通、合作和患者招募方面有着良好的记录：（1）UCSF Moffitt-Long医院，UCSF的主要教学医院;（2）加州大学旧金山分校弗雷斯诺/社区区域医疗中心，一个主要的医疗中心，照顾病人在加州的中央谷位于弗雷斯诺，CA;（3）加州大学戴维斯医学中心;及（4）斯坦福大学医学中心。因此，加州网络将由加州北部的四个主要医疗中心组成，这些中心的总人口约为1200万人。每个研究中心都有一名具有ARDS网络2经验的成熟且积极主动的研究协调员和重症监护研究员。为了响应该RFA，每家临床试验机构都增加了一名具有丰富临床试验经验的急诊科研究者。此外 我们作为ARDS网络2的一部分开展工作，并开展基于急诊科的临床试验，加州网络拥有与当前RFA高度相关的重要专业知识。我们的主要研究集中在临床标准上，以在治疗前识别有ARDS风险的患者。 正压通气的开始以及长期以来对ARDS新疗法的临床前和临床关注。事实上，Matthay博士是一项正在进行的NHLBI资助的1/2a期临床试验的主要研究者，该试验是针对中重度ARDS患者的同种异体骨髓源性人间充质干细胞，该试验将在PETAL网络开始之前完成。我们提出了两个临床方案，一个是针对在发生ARDS之前有早期肺损伤的患者，这些患者可以在急诊科识别，另一个是针对重症监护室的严重ARDS患者。第一个方案是3期试验，以测试静脉注射重组人角质细胞生长因子对符合ARDS标准之前的早期肺损伤患者的治疗价值。这些患者将主要在急诊科进行识别，当他们在胸片上有双侧肺浸润，需要超过2升的补充氧气，但还不需要正压通气。第二个方案是一项2b期试验，旨在测试同种异体骨髓来源的人间充质干细胞治疗重症监护室中中度至重度ARDS（PaO2/FiO2 <200 mm Hg）患者的潜在治疗价值。