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

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, a...