Design and Rationale of the Reevaluation of Systemic Early Neuromuscular Blockade Trial for Acute Respiratory Distress Syndrome

Abstract

The Reevaluation of Systemic Early Neuromuscular Blockade (ROSE) trial is a multicenter, randomized trial designed to assess the efficacy and safety of early neuromuscular blockade in patients with moderate to severe acute respiratory distress syndrome. This document provides background for interpretation of the trial results, and highlights unique design approaches that may inform future trials of acute illness. We describe the process by which ROSE was chosen as the inaugural trial of the multidisciplinary Prevention and Early Treatment of Acute Lung Injury Network, provide the trial methodology using the Consolidated Standards of Reporting Trials framework, and discuss key design challenges and their resolution. Four key design issues proved challenging-feasibility, choice of sedation depth in the control group, impact of emphasizing early treatment on enrollment criteria and protocol execution, and choice of positive end-expiratory pressure strategy. We used literature, an iterative consensus model, and internal surveys of current practice to inform design choice. ROSE will provide definitive, Consolidated Standards of Reporting Trials adherent data on early neuromuscular blockade for future patients with acute respiratory distress syndrome. Our multidisciplinary approach to trial design may be of use to other trials of acute illness. Clinical trial registered with www.clinicaltrials.gov (NCT02509078).

Keywords: adult; clinical trial; interdisciplinary communication; methods; respiratory distress syndrome.

Figure 1.

The Prevention and Early Treatment of Acute Lung Injury (PETAL) Network. Each of the 12 clinical centers is comprised of a lead academic medical center, with one or more affiliated satellite recruiting institutions, for a total of 48 Network hospitals, and are overseen by one Clinical Coordinating Center (CCC). The PETAL Steering Committee is composed of a chairperson, an intensive care unit investigator, and a second investigator from a different acute care specialty (e.g., emergency medicine, surgery, anesthesiology) from each clinical center, the CCC, and NHLBI project officers (map courtesy of Dr. David J. Wallace, University of Pittsburgh, Pittsburgh, PA).