This proposal is a response to the RFA-HL-14-015 for the coordinating center of the Clinical Trials Network for the Prevention and Early Treatment of Acute Lung Injury (PETAL) Network. We propose to provide leadership in the design, analysis and conduct of the studies of the PETAL Network and to provide the infrastructure and communications that will create a cohesive and productive group. Over the past 18 years we have served as the coordinating center of the Acute Respiratory Distress Syndrome (ARDS) Network under the leadership of an experienced clinical trials statistician and an acute care physician. We recently published our approach to the statistical and logistics issues of the ARDS Network. We propose to enhance those methods to improve performance of these activities for PETAL. Our proposal for the PETAL network focuses on the novel challenges of prevention trials. We suggest that the feasibility of a prevention trial depends on the choice of endpoint, in particular that studies using mortality as the primary endpoint would not be feasible with a conventional trial design and other clinical endpoints may be problematic. The optimal endpoint would be the occurrence of ARDS or a measure of the clinical consequences of ARDS. The proposal discusses the issues of cluster randomized trials and adaptive designs. We discuss the statistical and scientific issues in creating a biomarker resource for the PETAL Network. We also describe our proposals to increase productivity of the network by implementing an efficient IRB review process, plans for applying a computer-assisted technique to set network priorities, and plans for soliciting community involvement on an ongoing basis. We describe the methods we will use to provide the needed infrastructure (such as a remote data and trial management system) and the coordination of all network activities: data quality control, protocol compliance, protocol initiation, randomization, drug distribution, sample management, adverse event reporting, statistical reporting, data dissemination, communication, and logistics.

Public Health Relevance

Acute Respiratory Distress Syndrome (ARDS) is a life threatening lung condition that may develop after severe infections or trauma and requires mechanical ventilation and admission to an ICU. Each year in the United States there are an estimated 190,600 cases of ARDS which are associated with 74,500 deaths and 3.6 million hospital days. The proposed PETAL Network will seek to find the first specific treatment for ARDS or a method of prevention and has the potential to save thousands of lives annually. .

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project--Cooperative Agreements (U01)
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Reineck, Lora A
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Massachusetts General Hospital
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Huang, David T; Angus, Derek C; Moss, Marc et al. (2017) Design and Rationale of the Reevaluation of Systemic Early Neuromuscular Blockade Trial for Acute Respiratory Distress Syndrome. Ann Am Thorac Soc 14:124-133
Sjoding, Michael W; Brown, Samuel M; Moss, Marc et al. (2017) Reply: Validity of the Posttraumatic Stress Symptoms-14 Instrument in Acute Respiratory Failure Survivors. Ann Am Thorac Soc 14:1048-1049
Jolley, Sarah E; Hough, Catherine L; Clermont, Gilles et al. (2017) Relationship between Race and the Effect of Fluids on Long-term Mortality after Acute Respiratory Distress Syndrome. Secondary Analysis of the National Heart, Lung, and Blood Institute Fluid and Catheter Treatment Trial. Ann Am Thorac Soc 14:1443-1449
Brown, Samuel M; Duggal, Abhijit; Hou, Peter C et al. (2017) Nonlinear Imputation of PaO2/FIO2 From SpO2/FIO2 Among Mechanically Ventilated Patients in the ICU: A Prospective, Observational Study. Crit Care Med 45:1317-1324
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Brown, Samuel M; Grissom, Colin K; Moss, Marc et al. (2016) Nonlinear Imputation of Pao2/Fio2 From Spo2/Fio2 Among Patients With Acute Respiratory Distress Syndrome. Chest 150:307-13
Prescott, Hallie C; Calfee, Carolyn S; Thompson, B Taylor et al. (2016) Toward Smarter Lumping and Smarter Splitting: Rethinking Strategies for Sepsis and Acute Respiratory Distress Syndrome Clinical Trial Design. Am J Respir Crit Care Med 194:147-55
Gong, Michelle Ng; Thompson, B Taylor (2016) Acute respiratory distress syndrome: shifting the emphasis from treatment to prevention. Curr Opin Crit Care 22:21-37
Benthin, Cody; Pannu, Sonal; Khan, Akram et al. (2016) The Nature and Variability of Automated Practice Alerts Derived from Electronic Health Records in a U.S. Nationwide Critical Care Research Network. Ann Am Thorac Soc 13:1784-1788
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