The PETAL RFA is an exciting initiative to create a multi-disciplinary network that can develop and conduct multi-center clinical trials to evaluate promising therapies and approaches for preventing and/or treating acute respiratory distress syndrome (ARDS). We propose participation in this network. The lead institution for this proposal is Beth Israel Deaconess Medical Center (BIDMC), and satellite sites are Massachusetts General Hospital (MGH) and the University of Mississippi. In aggregate, our site possesses a uniquely strong track record of pre- existing collaboration between emergency medicine, anesthesiologists and intensive care physicians, as well as between our individual study sites. This experience and expertise directly addresses the intent of the proposal. Our research team has a sustained, proven track record of successful, high-impact studies in sepsis and ARDS spanning emergency medicine, perioperative medicine and critical care. Our site is already serves as the coordinating center for the Lung Injury Prevention Trial with Aspirin (LIPS-A) which is in many ways the prototype for the type of study envisioned for the PETAL network. Thus, we are ideally positioned to create an extremely high-performing PETAL clinical center, as well as to contribute to network leadership and scientific direction. We also submit two proposals for clinical studies to be undertaken by the PETAL network. Both of these studies are based upon strong preliminary data from our institutions. The first study will examine the ability of rosuvastatin to prevent development of ARDS in patients at risk for development of the syndrome. While statin drugs have previously been tested as a treatment for ARDS there is substantial evidence to suggest that they may be more effective as a prevention strategy. This study builds on our success as the clinical coordinating center of the LIPS-A study. Our second proposed study will test the ability of using personalized physiology, the patient's own pleural pressure as measured using esophageal balloons, to set the level of positive end-expiratory pressure in patients with established ARDS. This proposal will support a phase 3 trial of this promising modality. The expertise and experience of the investigators involved in this proposal will allow the BIDMC clinical site to contribute substantially to the scientific success of the PETAL network.
Acute Respiratory Distress Syndrome (ARDS) is common, lethal, and expensive, and represents an important public health threat. The associated mortality in ARDS exceeds 30% and accounts for 74,500 US deaths annually. Prevention and early treatment of ARDS therefore represents a promising focus of research in this arena: effective prevention of ALI will likely save more lives and further reduce dysfunction and healthcare cost compared with instituting treatment after the development of the fulminant syndrome that is often accompanied by extra-pulmonary organ failures.
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